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Basios A, Chatzi CA, Markozannes G, Ntzani EE, Barkas F, Tsilidis KK, Rizzo M, Kalampoki A, Rizos EC. Adherence to statins and development of atherosclerosis-related events. A systematic review and meta-analysis. J Diabetes Complications 2025; 39:109040. [PMID: 40403434 DOI: 10.1016/j.jdiacomp.2025.109040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Accepted: 04/12/2025] [Indexed: 05/24/2025]
Abstract
BACKGROUND Adherence to lipid-lowering treatment (LLT) is of paramount importance for the prevention of atherosclerosis-related events (ASCVD). The threshold for someone to be adherent is ≥80 % of the total prescribed medication. We conducted a meta-analysis to assess how adherence to LLT affects the development of ASCVD. METHODS We searched PubMed (up to February 2025) for randomized controlled trials, cohorts and nested case control studies that assessed adherence to LLT. We performed random effects meta-analysis with primary outcome the development of ASCVD based on the level of adherence to LLT. RESULTS We included 66 articles corresponding to 3,345,718 individuals. All studies evaluated statins as LLT. Good vs. poor statin adherence reduced by 35 % the risk for all-cause mortality (RR:0.65; 95%CI: 0.56-0.76; I2 = 98 %), 24 % for any cardiovascular (CV) event (RR:0.76; 95%CI: 0.72-0.80; I2 = 90 %), 30 % for myocardial infarction (MI) (RR:0.70; 95%CI: 0.62-0.80; I2 = 90 %) and 32 % for stroke (RR:0.68; 95%CI: 0.58-0.79; I2 = 81 %). For participants without established ASCVD, statin adherence reduced by 32 % the risk for any CV event (RR:0.68; 95%CI: 0.46-1.00; I2 = 97 %). For those with established ASCVD, statin adherence reduced by 25 % the risk for any CV event (RR:0.75; 95%CI: 0.64-0.88; I2 = 64 %), 51 % for MI (RR:0.49; 95%CI: 0.32-0.73; I2 = 80 %) and 50 % for stroke (RR:0.50; 95%CI: 0.26-0.97; I2 = 87 %). Statin discontinuation increased by 90 % the mortality risk (RR:1.90; 95%CI: 1.33-2.71; I2 = 87 %). Even good vs. intermediate adherence (40 %-79 %) decreased by 32 % the risk for any CV event (RR:0.68; 95%CI: 0.60-0.76; I2 = 94 %). Sensitivity analyses including studies with different than the standard (≥80 %) threshold did not differ from the main results. CONCLUSION Statin adherence is of paramount importance to reduce ASCVD risk and mortality. Understanding adherence patterns or barriers and ensuring consistent adherence to LLT by tailored interventions should be a key priority in clinical practice and healthcare policies.
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Affiliation(s)
| | | | - Georgios Markozannes
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Evangelia E Ntzani
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Health Services, Policy and Practice, School of Public Health, Brown University, RI, USA
| | - Fotios Barkas
- Department of Internal Medicine, University of Ioannina School of Medicine, Ioannina, Greece
| | - Konstantinos K Tsilidis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Manfredi Rizzo
- School of Medicine, Promise Department, University of Palermo, Italy; Ras Al Khaimah Medical and Health Sciences University, RAK, United Arab Emirates
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Lubieniecki P, Lewandowski Ł, Wołyniec M, Połtyn-Zaradna K, Zatońska K, Szuba A. The Dynamics of Cardiovascular Risk-An Analysis of the Prospective Urban Rural Epidemiology (PURE) Poland Cohort Study. J Clin Med 2024; 13:3728. [PMID: 38999293 PMCID: PMC11242048 DOI: 10.3390/jcm13133728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 06/13/2024] [Accepted: 06/21/2024] [Indexed: 07/14/2024] Open
Abstract
Background: The purpose of this study was to analyze the major cardiovascular risk (CVR) factors and their trends in the study population. Methods: The results of subjects in the Polish Prospective Urban and Rural Epidemiological Study (PURE) study group were interpreted. CVR was calculated for each participant according to the Systematic Coronary Risk Evaluation (SCORE2) scale or the Systematic Coronary Risk Evaluation-Older Persons (SCORE2-OP) scale. Data from the beginning of the analysis (2013) and nine years later (2022) were included. In addition, the use of lipid-lowering therapy (LLT) and meeting the low-density lipoprotein cholesterol (LDL-c) target criterion at the beginning and end of the study were analyzed. Results: Patients in the high and very high CVR groups who had abnormal LDL-c results accounted for 64% and 91% of their group in 2013 and 70% and 92% in 2022, respectively. Conclusions: Regardless of age, patients using LLT at the start of the analysis had a greater increase in future CVR, especially if they had lipid abnormalities at the start of the study. This may be due to reverse causality and multimorbidity in these patients, highlighting the importance of appropriate treatment of lipid abnormalities.
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Affiliation(s)
- Paweł Lubieniecki
- Clinical Department of Diabetology and Internal Disease, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland
| | - Łukasz Lewandowski
- Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland
| | - Maria Wołyniec
- Population Health Department, Wroclaw Medical University, 50-345 Wrocław, Poland
| | | | - Katarzyna Zatońska
- Population Health Department, Wroclaw Medical University, 50-345 Wrocław, Poland
- Calisia University, 62-800 Kalisz, Poland
| | - Andrzej Szuba
- Clinical Department of Angiology and Internal Disease, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland
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Mazhar F, Hjemdahl P, Sjölander A, Kahan T, Jernberg T, Carrero JJ. Intensity of and adherence to lipid-lowering therapy as predictors of goal attainment and major adverse cardiovascular events in primary prevention. Am Heart J 2024; 269:118-130. [PMID: 38109988 DOI: 10.1016/j.ahj.2023.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 11/25/2023] [Accepted: 12/10/2023] [Indexed: 12/20/2023]
Abstract
BACKGROUND The effectiveness of lipid-lowering therapy (LLT) for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in routine care may depend on treatment intensity and adherence. METHODS Observational study of adults with newly initiated LLT for primary prevention of ASCVD in Stockholm, Sweden, during 2017-2021. Study exposures were LLT adherence [proportion of days covered (PDC)], LLT intensity (expected reduction of LDL cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity were calculated during the previous 12 months, and the patients estimated ASCVD risk was categorized. Study outcomes were major adverse cardiovascular events (MACE) and LDL-C goal attainment. RESULTS Thirty-six thousand two hundred eighty-three individuals (mean age 63 years, 47% women, median follow-up 2 years), with a baseline low-moderate (40%), high (49%), and very-high (11%) ASCVD risk started LLT. Increases in LLT adherence, intensity, or adherence-adjusted intensity of 10% over 1 year were associated with lower risks of MACE (with hazard ratios of 0.95 [95% CI, 0.93-0.98]; 0.93 [0.86-1.00]; and 0.90 [0.85-0.95], respectively) and higher odds of attaining LDL goals. Patients with good adherence (≥80%) had similar risks of MACE and similar odds ratios for LDL-C goal attainment with low-moderate and high-intensity LLT. Treatment discontinuation was associated with increased MACE risk. The relative and absolute benefits of good adherence were greatest in patients with very high ASCVD risk. CONCLUSION In routine-care primary prevention, better adherence to LLT was associated with a lower risk of MACE across all treatment intensities. Improving adherence is especially important among patients with very high ASCVD risk.
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Affiliation(s)
- Faizan Mazhar
- Department of Medical Epidemiology and Biostatistics, Campus Solna, Karolinska Institutet, Stockholm, Sweden.
| | - Paul Hjemdahl
- Department of Medicine Solna, Clinical Epidemiology Unit/Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Arvid Sjölander
- Department of Medical Epidemiology and Biostatistics, Campus Solna, Karolinska Institutet, Stockholm, Sweden
| | - Thomas Kahan
- Department of Clinical Sciences, Karolinska Institutet, Division of Cardiovascular Medicine, Danderyd Hospital, Stockholm, Sweden
| | - Tomas Jernberg
- Department of Clinical Sciences, Karolinska Institutet, Division of Cardiovascular Medicine, Danderyd Hospital, Stockholm, Sweden
| | - Juan Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Campus Solna, Karolinska Institutet, Stockholm, Sweden; Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Danderyd, Sweden
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Baratta F, Angelico F, Del Ben M. Challenges in Improving Adherence to Diet and Drug Treatment in Hypercholesterolemia Patients. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:5878. [PMID: 37239603 PMCID: PMC10218349 DOI: 10.3390/ijerph20105878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 04/11/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023]
Abstract
Poor adherence to chronic disease treatment may seriously compromise the effectiveness of therapy, characterizing itself as a critical element for the population's health, both from the point of view of quality of life and health economics. The causes of low adherence are many and can depend on the patient, the physician and the healthcare system. Low adherence to dietary recommendations and lipid-lowering drug therapy for hypercholesterolemia is a widespread phenomenon that may strongly limit the great advantages of serum lipid reduction strategies in primary and secondary cardiovascular prevention. Many patients discontinue treatment, and adherence decreases with time. Increasing therapeutic adherence can have a much greater impact on the health of the population than any other therapeutic advance. There are numerous strategies to increase therapy adherence according to behavior change theories. They concern the doctor and the patient. Some must be implemented at the time of prescription, others later during the follow-up. The active role of the patient in the therapeutic decision and the shared definition of LDL cholesterol targets are of paramount importance. The aim of this narrative review is to summarize evidence on current levels of adherence to lipid-lowering strategies, the causes of the lack of adequate adherence and possible physician-applicable strategies to improve it.
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Affiliation(s)
- Francesco Baratta
- Department of Clinical Internal, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
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Corral-Partearroyo C, Sánchez-Viñas A, Gil-Girbau M, Peñarrubia-María MT, Aznar-Lou I, Serrano-Blanco A, Carbonell-Duacastella C, Gallardo-González C, Olmos-Palenzuela MDC, Rubio-Valera M. Improving Initial Medication Adherence to cardiovascular disease and diabetes treatments in primary care: Pilot trial of a complex intervention. Front Public Health 2022; 10:1038138. [PMID: 36561857 PMCID: PMC9764337 DOI: 10.3389/fpubh.2022.1038138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/10/2022] [Indexed: 12/12/2022] Open
Abstract
Introduction The Initial Medication Adherence (IMA) intervention is a multidisciplinary and shared decision-making intervention to improve initial medication adherence addressed to patients in need of new treatments for cardiovascular diseases and diabetes in primary care (PC). This pilot study aims to evaluate the feasibility and acceptability of the IMA intervention and the feasibility of a cluster-RCT to assess the effectiveness and cost-effectiveness of the intervention. Methods A 3-month pilot trial with an embedded process evaluation was conducted in five PC centers in Catalonia (Spain). Electronic health data were descriptively analyzed to test the availability and quality of records of the trial outcomes (initiation, implementation, clinical parameters and use of services). Recruitment and retention rates of professionals were analyzed. Twenty-nine semi-structured interviews with professionals (general practitioners, nurses, and community pharmacists) and patients were conducted to assess the feasibility and acceptability of the intervention. Three discussion groups with a total of fifteen patients were performed to review and redesign the intervention decision aids. Qualitative data were thematically analyzed. Results A total of 901 new treatments were prescribed to 604 patients. The proportion of missing data in the electronic health records was up to 30% for use of services and around 70% for clinical parameters 5 months before and after a new prescription. Primary and secondary outcomes were within plausible ranges and outliers were barely detected. The IMA intervention and its implementation strategy were considered feasible and acceptable by pilot-study participants. Low recruitment and retention rates, understanding of shared decision-making by professionals, and format and content of decision aids were the main barriers to the feasibility of the IMA intervention. Discussion Involving patients in the decision-making process is crucial to achieving better clinical outcomes. The IMA intervention is feasible and showed good acceptability among professionals and patients. However, we identified barriers and facilitators to implementing the intervention and adapting it to a context affected by the COVID-19 pandemic that should be considered before launching a cluster-RCT. This pilot study identified opportunities for refining the intervention and improving the design of the definitive cluster-RCT to evaluate its effectiveness and cost-effectiveness. Clinical trial registration ClinicalTrials.gov, identifier NCT05094986.
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Affiliation(s)
- Carmen Corral-Partearroyo
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain,Department of Paediatrics, Obstetrics, Gynaecology and Preventive Medicine, Univ Autonoma de Barcelona, Bellaterra, Spain,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública), Madrid, Spain
| | - Alba Sánchez-Viñas
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública), Madrid, Spain,Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain
| | - Montserrat Gil-Girbau
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain,Parc Sanitari Sant Joan de Déu,Sant Boi de Llobregat, Spain,Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), Barcelona, Spain
| | - María Teresa Peñarrubia-María
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública), Madrid, Spain,Primary Care Centre Bartomeu Fabrés Anglada, Direcció D'Atenció Primària Regió Metropolitana Sud, Institut Català de la Salut, Barcelona, Spain,Unitat de Suport a la Recerca Regió Metropolitana Sud, Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - Ignacio Aznar-Lou
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública), Madrid, Spain
| | - Antoni Serrano-Blanco
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública), Madrid, Spain,Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain,Parc Sanitari Sant Joan de Déu,Sant Boi de Llobregat, Spain
| | - Cristina Carbonell-Duacastella
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública), Madrid, Spain,Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain
| | - Carmen Gallardo-González
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain,Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), Barcelona, Spain,Primary Care Centre Bartomeu Fabrés Anglada, Direcció D'Atenció Primària Regió Metropolitana Sud, Institut Català de la Salut, Barcelona, Spain,Unitat de Suport a la Recerca Regió Metropolitana Sud, Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - Maria del Carmen Olmos-Palenzuela
- Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), Barcelona, Spain,Primary Care Centre Bartomeu Fabrés Anglada, Direcció D'Atenció Primària Regió Metropolitana Sud, Institut Català de la Salut, Barcelona, Spain
| | - Maria Rubio-Valera
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain,Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública), Madrid, Spain,Parc Sanitari Sant Joan de Déu,Sant Boi de Llobregat, Spain,*Correspondence: Maria Rubio-Valera
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Doganer YC, Aydogan U, Kaplan U, Gormel S, Rohrer JE, Yuksel UC. Statin adherence in patients with high cardiovascular risk: a cross-sectional study. Postgrad Med 2022; 135:361-369. [PMID: 36345979 DOI: 10.1080/00325481.2022.2144030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
OBJECTIVES Statin adherence is an essential problem although lifetime medication is recommended especially in patients with high cardiovascular risk. The importance of perceived risk as a predictor of adherence among cardiology patients has not been fully explored. This study aimed to test the importance of perceived risk as a predictor of statin adherence amongst hypercholesterolemic patients to identify predictors associated with poor adherence. METHODS This cross-sectional study was conducted at cardiology outpatient clinics of the University hospital in Ankara, Turkey. A total of 327 consecutive patients with high CV risk were recruited. Self-reported Morisky Green Levine Medication Adherence Scale was used to assess statin adherence. RESULTS Of the patients studied, 34.5% had concerns about side effects. Also, the mean age was 63.85 ± 11.29 years, 66.1% were men, 32.4% applied non-drug alternative therapies, 53.2% had a Mediterranean-style diet and 20.8% checked their lipid values irregularly. Participants reported 50.2% high, 30% moderate, and 19.9% low statin medication adherence. Low-density lipoprotein cholesterol (LDL-C), Total Cholesterol (TC), Triglyceride (TG) and high-density lipoprotein (HDL) control rates were 44.6%, 74.3%, 61.5% and 41.6%. On multiple logistic regression, concern about side effects was associated with a statistically significant quadruple elevation of odds of non-adherence. Also, being male, former smokers, not having complementary interventions, having regular visits, being educated for more than 5 years, having low depressive symptom scores, living in a rural, being never or former smokers, employee were significant predictors of high medication adherence scores. CONCLUSION Approximately half of the patients reported high medication adherence. Proper strategies to improve adherence would include patient education efforts focused on patients with concerns about side effects and those who are female, less educated, current smokers, interested in complementary interventions, have irregular follow-up visits, and have depressive symptoms. Brief medication adherence scales may facilitate the assessment of patients' adherence.
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Affiliation(s)
- Yusuf Cetin Doganer
- Department of Family Medicine, University of Health Sciences, Gulhane School of Medicine, Ankara, Turkey
| | - Umit Aydogan
- Department of Family Medicine, University of Health Sciences, Gulhane School of Medicine, Ankara, Turkey
| | - Umit Kaplan
- Ministry of National Defence, Ankara, Turkey
| | - Suat Gormel
- Department of Cardiology, University of Health Sciences, Gulhane Training and Research Hospital, Ankara, Turkey
| | | | - Uygar Cagdas Yuksel
- Department of Cardiology, University of Health Sciences, Gulhane Training and Research Hospital, Ankara, Turkey
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Corral-Partearroyo C, Sánchez-Viñas A, Gil-Girbau M, Peñarrubia-María MT, Aznar-Lou I, Gallardo-González C, Olmos-Palenzuela MDC, Rubio-Valera M. Complex multidisciplinary intervention to improve Initial Medication Adherence to cardiovascular disease and diabetes treatments in primary care (the IMA-cRCT study): mixed-methods process evaluation protocol. BMJ Open 2022; 12:e067468. [PMID: 36316078 PMCID: PMC9628671 DOI: 10.1136/bmjopen-2022-067468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 10/10/2022] [Indexed: 11/03/2022] Open
Abstract
INTRODUCTION Medication non-initiation, or primary non-adherence, is a persistent public health problem that increases the risk of adverse clinical outcomes. The initial medication adherence (IMA) intervention is a complex multidisciplinary intervention to improve adherence to cardiovascular and diabetes treatments in primary care by empowering the patient and promoting informed prescriptions based on shared decision-making. This paper presents the development and implementation strategy of the IMA intervention and the process evaluation protocol embedded in a cluster randomised controlled trial (the IMA-cRCT) to understand and interpret the outcomes of the trial and comprehend the extent of implementation and fidelity, the active mechanisms of the IMA intervention and in what context the intervention is implemented and works. METHODS AND ANALYSIS We present the protocol for a mixed-methods process evaluation including quantitative and qualitative methods to measure implementation and fidelity and to explore the active mechanisms and the interactions between the intervention, participants and its context. The process evaluation will be conducted in primary care centres and community pharmacies from the IMA-cRCT, and participants include healthcare professionals (general practitioners, nurses and community pharmacists) as well as patients. Quantitative data collection methods include data extraction from the intervention operative records, patient clinical records and participant feedback questionnaires, whereas qualitative data collection involves semistructured interviews, focus groups and field diaries. Quantitative and qualitative data will be analysed separately and triangulated to produce deeper insights and robust results. ETHICS AND DISSEMINATION Ethical approval has been obtained from the Research Ethics Comittee (CEIm) at IDIAP Jordi Gol (codeCEIm 21/051 P). Findings will be disseminated through publications and conferences, as well as presentations to healthcare professionals and stakeholders from healthcare organisations. TRIAL REGISTRATION NUMBER NCT05026775.
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Affiliation(s)
- Carmen Corral-Partearroyo
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Parc Sanitari Sant Joan de Deu, Institut de Recerca Sant Joan de Deu, St Boi de Llobregat, Catalunya, Spain
- Department of Paediatrics, Obstetrics, Gynaecology and Preventive Medicine, Universitat Autonoma de Barcelona, Bellaterra, Catalunya, Spain
| | - Alba Sánchez-Viñas
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Parc Sanitari Sant Joan de Deu, Institut de Recerca Sant Joan de Deu, St Boi de Llobregat, Catalunya, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Catalunya, Spain
| | - Montserrat Gil-Girbau
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Parc Sanitari Sant Joan de Deu, Institut de Recerca Sant Joan de Deu, St Boi de Llobregat, Catalunya, Spain
- Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), Barcelona, Spain
| | - Maria Teresa Peñarrubia-María
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Parc Sanitari Sant Joan de Deu, Institut de Recerca Sant Joan de Deu, St Boi de Llobregat, Catalunya, Spain
- Unitat de Suport a la Recerca Regió Metropolitana Sud, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Catalunya, Spain
| | - Ignacio Aznar-Lou
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Parc Sanitari Sant Joan de Deu, Institut de Recerca Sant Joan de Deu, St Boi de Llobregat, Catalunya, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Comunidad de Madrid, Spain
| | - Carmen Gallardo-González
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Parc Sanitari Sant Joan de Deu, Institut de Recerca Sant Joan de Deu, St Boi de Llobregat, Catalunya, Spain
- Unitat de Suport a la Recerca Regió Metropolitana Sud, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Catalunya, Spain
| | - María Del Carmen Olmos-Palenzuela
- Primary Care Centre Bartomeu Fabrés Anglada, Institut Català de la Salut Gerència Territorial Metropolitana Sud, Barcelona, Catalunya, Spain
| | - Maria Rubio-Valera
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Parc Sanitari Sant Joan de Deu, Institut de Recerca Sant Joan de Deu, St Boi de Llobregat, Catalunya, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Comunidad de Madrid, Spain
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Sánchez-Viñas A, Corral-Partearroyo C, Gil-Girbau M, Peñarrubia-María MT, Gallardo-González C, Olmos-Palenzuela MDC, Aznar-Lou I, Serrano-Blanco A, Rubio-Valera M. Effectiveness and cost-effectiveness of an intervention to improve Initial Medication Adherence to treatments for cardiovascular diseases and diabetes in primary care: study protocol for a pragmatic cluster randomised controlled trial and economic model (the IMA-cRCT study). BMC PRIMARY CARE 2022; 23:170. [PMID: 35790915 PMCID: PMC9255541 DOI: 10.1186/s12875-022-01727-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 05/04/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Between 2 and 43% of patients who receive a new prescription in PC do not initiate their treatments. Non-initiation is associated with poorer clinical outcomes, more sick leave and higher costs to the healthcare system. Existing evidence suggests that shared decision-making positively impacts medication initiation. The IMA-cRCT assesses the effectiveness of the IMA intervention in improving adherence and clinical parameters compared to usual care in patients with a new treatment for cardiovascular disease and diabetes prescribed in PC, and its cost-effectiveness, through a cRCT and economic modelling. METHODS The IMA intervention is a shared decision-making intervention based on the Theoretical Model of Non-initiation. A cRCT will be conducted in 24 PC teams in Catalonia (Spain), randomly assigned to the intervention group (1:1), and community pharmacies in the catchment areas of the intervention PC teams. Healthcare professionals in the intervention group will apply the intervention to all patients who receive a new prescription for cardiovascular disease or diabetes treatment (no other prescription from the same pharmacological group in the previous 6 months). All the study variables will be collected from real-world databases for the 12 months before and after receiving a new prescription. Effectiveness analyses will assess impact on initiation, secondary adherence, cardiovascular risk, clinical parameters and cardiovascular events. Cost-effectiveness analyses will be conducted as part of the cRCT from a healthcare and societal perspective in terms of extra cost per cardiovascular risk reduction and improved adherence; all analyses will be clustered. Economic models will be built to assess the long-term cost-effectiveness of the IMA intervention, in terms of extra cost for gains in QALY and life expectancy, using clinical trial data and data from previous studies. DISCUSSION The IMA-cRCT represents an innovative approach to the design and evaluation of behavioural interventions that use the principles of complex interventions, pragmatic trials and implementation research. This study will provide evidence on the IMA intervention and on a new methodology for developing and evaluating complex interventions. The results of the study will be disseminated among stakeholders to facilitate its transferability to clinical practice. TRIAL REGISTRATION ClinicalTrials.gov, NCT05026775 . Registered 30th August 2021.
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Affiliation(s)
- Alba Sánchez-Viñas
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, c. Casanova 143, 08036, Barcelona, Spain
| | - Carmen Corral-Partearroyo
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain
- Department of Paediatrics, Obstetrics, Gynaecology and Preventive Medicine, Univ Autonoma de Barcelona, Bellaterra, Spain
| | - Montserrat Gil-Girbau
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain
- Parc Sanitari Sant Joan de Déu, Doctor Antoni Pujadas 42, 08830, Sant Boi de Llobregat, Spain
| | - M Teresa Peñarrubia-María
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Centre d'Atenció Primària Bartomeu Fabrés Anglada, Direcció D'Atenció Primària Regió Metropolitana Sud, Institut Català de la Salut, Barcelona, Spain
- Unitat de Suport a la Recerca Regió Metropolitana Sud, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - Carmen Gallardo-González
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain
- Centre d'Atenció Primària Bartomeu Fabrés Anglada, Direcció D'Atenció Primària Regió Metropolitana Sud, Institut Català de la Salut, Barcelona, Spain
- Unitat de Suport a la Recerca Regió Metropolitana Sud, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - María-Del-Carmen Olmos-Palenzuela
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain
- Centre d'Atenció Primària Bartomeu Fabrés Anglada, Direcció D'Atenció Primària Regió Metropolitana Sud, Institut Català de la Salut, Barcelona, Spain
| | - Ignacio Aznar-Lou
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain.
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
| | - Antoni Serrano-Blanco
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Parc Sanitari Sant Joan de Déu, Doctor Antoni Pujadas 42, 08830, Sant Boi de Llobregat, Spain
| | - Maria Rubio-Valera
- Health Technology Assessment in Primary Care and Mental Health (PRISMA) Research Group, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Parc Sanitari Sant Joan de Déu, Doctor Antoni Pujadas 42, 08830, Sant Boi de Llobregat, Spain
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9
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Petersen JM, Ranker LR, Barnard-Mayers R, MacLehose RF, Fox MP. A systematic review of quantitative bias analysis applied to epidemiological research. Int J Epidemiol 2021; 50:1708-1730. [PMID: 33880532 DOI: 10.1093/ije/dyab061] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/05/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Quantitative bias analysis (QBA) measures study errors in terms of direction, magnitude and uncertainty. This systematic review aimed to describe how QBA has been applied in epidemiological research in 2006-19. METHODS We searched PubMed for English peer-reviewed studies applying QBA to real-data applications. We also included studies citing selected sources or which were identified in a previous QBA review in pharmacoepidemiology. For each study, we extracted the rationale, methodology, bias-adjusted results and interpretation and assessed factors associated with reproducibility. RESULTS Of the 238 studies, the majority were embedded within papers whose main inferences were drawn from conventional approaches as secondary (sensitivity) analyses to quantity-specific biases (52%) or to assess the extent of bias required to shift the point estimate to the null (25%); 10% were standalone papers. The most common approach was probabilistic (57%). Misclassification was modelled in 57%, uncontrolled confounder(s) in 40% and selection bias in 17%. Most did not consider multiple biases or correlations between errors. When specified, bias parameters came from the literature (48%) more often than internal validation studies (29%). The majority (60%) of analyses resulted in >10% change from the conventional point estimate; however, most investigators (63%) did not alter their original interpretation. Degree of reproducibility related to inclusion of code, formulas, sensitivity analyses and supplementary materials, as well as the QBA rationale. CONCLUSIONS QBA applications were rare though increased over time. Future investigators should reference good practices and include details to promote transparency and to serve as a reference for other researchers.
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Affiliation(s)
- Julie M Petersen
- Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
| | - Lynsie R Ranker
- Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
| | - Ruby Barnard-Mayers
- Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
| | - Richard F MacLehose
- Division of Epidemiology and Community Health, University of Minnesota, School of Public Health, Minneapolis, MN, USA
| | - Matthew P Fox
- Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.,Department of Global Health, Boston University School of Public Health, Boston, MA, USA
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10
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Ryou IS, Chang J, Son JS, Ko A, Choi S, Kim K, Kim SM, Park SM. Association between CVDs and initiation and adherence to statin treatment in patients with newly diagnosed hypercholesterolaemia: a retrospective cohort study. BMJ Open 2021; 11:e045375. [PMID: 33827840 PMCID: PMC8031030 DOI: 10.1136/bmjopen-2020-045375] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVES To evaluate the association between incident cardiovascular disease (CVD) and initiation and adherence to statin treatment for primary prevention of CVD in patients with newly diagnosed hypercholesterolaemia. DESIGN A population-based retrospective cohort study. SETTING This study used National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) from Republic of Korea. PARTICIPANTS This study included 11 320 participants without previous history of CVD aged between 40 and 79 years who had elevated total cholesterol level (more than 240 mg/dL) and had initiated statin treatment within 24 months of the national health screening from 2004 to 2012 identified in the NHIS-HEALS. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome, CVD, was defined as first-ever admission or death due to ischaemic heart disease, acute myocardial infarction, revascularisation or stroke, or December 31 2013. The HRs of CVD according to statin adherence were calculated according to stratification by Systematic COronary Risk Evaluation. RESULTS Early statin initiation significantly lowered risk of CVD outcomes compared with late initiation (HR of late statin user, 1.24; 95% CI 1.02 to 2.51). Among early initiators, statin discontinuers had a significantly higher risk for CVD compared with persistent users (HR, 1.71; 95% CI 1.10 to 2.67), while statin reinitiators had an attenuated risk increase (HR 1.34, 95% CI 0.79 to 2.30). CONCLUSIONS Among statin users with newly diagnosed hypercholesterolaemia, early statin initiation is associated with lower CVD risk compared with late initiation. Furthermore, statin discontinuation is associated with increased risk of CVD, but reinitiation attenuated the risk.
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Affiliation(s)
- In Sun Ryou
- Family Medicine, Ewha Womans University School of Medicine, Seoul, Korea (the Republic of)
| | - Jooyoung Chang
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
| | - Joung Sik Son
- Family Medicine, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
| | - Ahryoung Ko
- Family Medicine, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
| | - Seulggie Choi
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
| | - Kyuwoong Kim
- Division of Cancer Control and Policy; National Cancer Survivorship Center, National Cancer Control Institute, National Cancer Center, Gyeonggi-do, Korea (the Republic of)
| | - Sung Min Kim
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
| | - Sang Min Park
- Department of Family Medicine, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
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11
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Tanner RM, Colantonio LD, Kilgore ML, Mefford MT, Chachappan DT, Mues KE, Safford MM, Rosenson RS, Muntner P. Low-density lipoprotein cholesterol levels among individuals experiencing statin-associated symptoms: Data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. J Clin Lipidol 2020; 14:720-729. [PMID: 32680814 PMCID: PMC9668077 DOI: 10.1016/j.jacl.2020.06.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 05/22/2020] [Accepted: 06/07/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND Guidelines recommend adults who discontinue statin therapy because of statin-associated symptoms be reinitiated. Low-density lipoprotein cholesterol (LDL-C) levels achieved after statin reinitiation are unknown. OBJECTIVE The objective of this study was to determine LDL-C levels after statin reinitiation. METHODS We analyzed data from 5498 participants in the REasons for Geographic And Racial Differences in Stroke study who reported ever taking a statin. We categorized participants according to their pattern of statin use including those taking a statin who did not experience statin-associated symptoms and continued treatment, and those who discontinued statins because of statin-associated symptoms and were not reinitiated, reinitiated and remained on treatment, and discontinued treatment after being reinitiated. Mortality and vascular event reduction with statin reinitiation was estimated using data from the Cholesterol-Lowering Treatment Trialists Collaboration. RESULTS After multivariable adjustment, LDL-C was 14.1 (95% CI: 9.9-18.3) mg/dL higher among participants reinitiated and taking a statin compared with those without statin-associated symptoms who continued statin therapy. Mean LDL-C was 18.1 mg/dL (95% CI: 13.0-23.1) and 27.5 mg/dL (95% CI: 20.7-34.4) lower among participants reinitiated and taking a statin compared with those who discontinued statin therapy and were not reinitiated and those who discontinued statins after being reinitiated, respectively. An LDL-C reduction of 18.1 mg/dL with statin reinitiation was projected to reduce all-cause and coronary heart disease mortality by 5.6% and 8.9%, respectively, and myocardial infarction or coronary heart disease death and major vascular events by 10.7% and 9.8%, respectively, over 5 years. CONCLUSION Reinitiating individuals who discontinue statin therapy may reduce LDL-C and cardiovascular risk.
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Affiliation(s)
- Rikki M Tanner
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Lisandro D Colantonio
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Meredith L Kilgore
- Department of Health Care Organization and Policy, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Matthew T Mefford
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Dayl T Chachappan
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Katherine E Mues
- The Center for Observational Research, Amgen Inc, Thousand Oaks, CA, USA
| | - Monika M Safford
- Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA
| | - Robert S Rosenson
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Paul Muntner
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
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12
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Zhao B, He X, Wu J, Yan S. Adherence to statins and its impact on clinical outcomes: a retrospective population-based study in China. BMC Cardiovasc Disord 2020; 20:282. [PMID: 32522146 PMCID: PMC7288497 DOI: 10.1186/s12872-020-01566-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 06/02/2020] [Indexed: 02/08/2023] Open
Abstract
Background While the benefit of adherence to statins on clinical outcomes has been proved, this benefit may be heterogeneous among patients who initiated statins for primary or secondary prevention purpose. This study aimed to investigate the impact of statin adherence on clinical outcomes among patients who initiated statins for primary and secondary prevention in China. Methods Adult patients in Tianjin Urban Employee Basic Medical Insurance database who initiated ≥2 prescriptions of statins from 2012 through 2013 were included and grouped into primary and secondary prevention subgroups according to their cardiovascular diseases (CVD) history during the prior 12-month baseline period. Proportion of days covered (PDC) was used to measure statin adherence in the initial 12-month follow-up. Clinical outcomes were measured by the incidence of major adverse cardiovascular events (MACE) during the 13th–24th months follow-up, and were compared between the patients with PDC ≥ 0.5 and patients with PDC < 0.5 using Cox regression models in primary and secondary prevention subgroups. Sensitivity analyses were conducted in propensity score matched groups. Results 99,655 patients were finally included. The mean (SD) PDC was 0.19 (0.15) in primary prevention subgroup (N = 34,372), with 5.4% patients had PDC ≥ 0.5. The patients with PDC ≥ 0.5 had a 37% reduced risk of MACE compared with patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 1.1% vs. 1.4%; all-adjusted HR = 0.63; 95% CI, 0.41–0.98). While, no significant difference was observed in the secondary prevention subgroup (N = 65,283) between patients with PDC ≥ 0.5 and patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 4.6% vs. 2.8%; all-adjusted HR = 1.08, 95% CI, 0.92–1.28). These findings were confirmed by the sensitivity analyses in propensity score matched groups. Conclusions Statin adherence was very poor in China, and statin adherence is associated with decreased risk of MACE in patients for primary prevention, while further exploration is needed for secondary prevention.
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Affiliation(s)
- Boya Zhao
- School of Pharmaceutical Science and Technology, Tianjin University, No 92 Weijin Road, Nankai District, Tianjin, 300072, China
| | - Xiaoning He
- School of Pharmaceutical Science and Technology, Tianjin University, No 92 Weijin Road, Nankai District, Tianjin, 300072, China
| | - Jing Wu
- School of Pharmaceutical Science and Technology, Tianjin University, No 92 Weijin Road, Nankai District, Tianjin, 300072, China.
| | - Shu Yan
- Pharmacy Department, Nankai Hospital, No.122 Sanwei Road. Nankai District, Tianjin, 300072, China.
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13
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Vilaplana-Carnerero C, Aznar-Lou I, Peñarrubia-María MT, Serrano-Blanco A, Fernández-Vergel R, Petitbò-Antúnez D, Gil-Girbau M, March-Pujol M, Mendive JM, Sánchez-Viñas A, Carbonell-Duacastella C, Rubio-Valera M. Initiation and Single Dispensing in Cardiovascular and Insulin Medications: Prevalence and Explanatory Factors. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E3358. [PMID: 32408626 PMCID: PMC7277594 DOI: 10.3390/ijerph17103358] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 05/08/2020] [Accepted: 05/10/2020] [Indexed: 11/16/2022]
Abstract
BACKGROUND Adherence problems have negative effects on health, but there is little information on the magnitude of non-initiation and single dispensing. OBJECTIVE The aim of this study was to estimate the prevalence of non-initiation and single dispensation and identify associated predictive factors for the main treatments prescribed in Primary Care (PC) for cardiovascular disease (CVD) and diabetes. METHODS Cohort study with real-world data. Patients who received a first prescription (2013-2014) for insulins, platelet aggregation inhibitors, angiotensin-converting enzyme inhibitors (ACEI) or statins in Catalan PC were included. The prevalence of non-initiation and single dispensation was calculated. Factors that explained these behaviours were explored. RESULTS At three months, between 5.7% (ACEI) and 9.1% (antiplatelets) of patients did not initiate their treatment and between 10.6% (statins) and 18.4% (ACEI) filled a single prescription. Body mass index, previous CVD, place of origin and having a substitute prescriber, among others, influenced the risk of non-initiation and single dispensation. CONCLUSIONS The prevalence of non-initiation and single dispensation of CVD medications and insulin prescribed in PC in is high. Patient and health-system factors, such as place of origin and type of prescriber, should be taken into consideration when prescribing new medications for CVD and diabetes.
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Affiliation(s)
- Carles Vilaplana-Carnerero
- Research and Development Unit, Institut de Recerca Sant Joan de Déu, 08830 Barcelona, Catalonia, Spain; (C.V.-C.); (I.A.-L.); (M.G.-G.); (A.S.-V.); (C.C.-D.)
- School of Pharmacy, University of Barcelona, 08028 Barcelona, Catalonia, Spain;
| | - Ignacio Aznar-Lou
- Research and Development Unit, Institut de Recerca Sant Joan de Déu, 08830 Barcelona, Catalonia, Spain; (C.V.-C.); (I.A.-L.); (M.G.-G.); (A.S.-V.); (C.C.-D.)
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública—CIBERESP), 28029 Madrid, Spain; (M.T.P.-M.); (A.S.-B.)
| | - María Teresa Peñarrubia-María
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública—CIBERESP), 28029 Madrid, Spain; (M.T.P.-M.); (A.S.-B.)
- Primary Care Research Institute (IDIAP Jordi Gol), 08007 Barcelona, Spain; (R.F.-V.); (J.M.M.)
- Catalan Institute of Health, 08028 Barcelona, Spain;
| | - Antoni Serrano-Blanco
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública—CIBERESP), 28029 Madrid, Spain; (M.T.P.-M.); (A.S.-B.)
- Parc Sanitari Sant Joan de Déu, 08830 Sant Boi de Llobregat, Catalonia, Spain
| | - Rita Fernández-Vergel
- Primary Care Research Institute (IDIAP Jordi Gol), 08007 Barcelona, Spain; (R.F.-V.); (J.M.M.)
- Catalan Institute of Health, 08028 Barcelona, Spain;
| | | | - Montserrat Gil-Girbau
- Research and Development Unit, Institut de Recerca Sant Joan de Déu, 08830 Barcelona, Catalonia, Spain; (C.V.-C.); (I.A.-L.); (M.G.-G.); (A.S.-V.); (C.C.-D.)
- School of Pharmacy, University of Barcelona, 08028 Barcelona, Catalonia, Spain;
- Primary Care Prevention and Health Promotion Research Network, 08007 Barcelona, Catalonia, Spain
| | - Marian March-Pujol
- School of Pharmacy, University of Barcelona, 08028 Barcelona, Catalonia, Spain;
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública—CIBERESP), 28029 Madrid, Spain; (M.T.P.-M.); (A.S.-B.)
| | - Juan Manuel Mendive
- Primary Care Research Institute (IDIAP Jordi Gol), 08007 Barcelona, Spain; (R.F.-V.); (J.M.M.)
- Catalan Institute of Health, 08028 Barcelona, Spain;
- Primary Care Prevention and Health Promotion Research Network, 08007 Barcelona, Catalonia, Spain
| | - Alba Sánchez-Viñas
- Research and Development Unit, Institut de Recerca Sant Joan de Déu, 08830 Barcelona, Catalonia, Spain; (C.V.-C.); (I.A.-L.); (M.G.-G.); (A.S.-V.); (C.C.-D.)
| | - Cristina Carbonell-Duacastella
- Research and Development Unit, Institut de Recerca Sant Joan de Déu, 08830 Barcelona, Catalonia, Spain; (C.V.-C.); (I.A.-L.); (M.G.-G.); (A.S.-V.); (C.C.-D.)
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública—CIBERESP), 28029 Madrid, Spain; (M.T.P.-M.); (A.S.-B.)
| | - Maria Rubio-Valera
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública—CIBERESP), 28029 Madrid, Spain; (M.T.P.-M.); (A.S.-B.)
- Parc Sanitari Sant Joan de Déu, 08830 Sant Boi de Llobregat, Catalonia, Spain
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14
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Dopheide JF, Veit J, Ramadani H, Adam L, Papac L, Vonbank A, Kaspar M, Rastan A, Baumgartner I, Drexel H. Adherence to statin therapy favours survival of patients with symptomatic peripheral artery disease. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2019; 7:263-270. [PMID: 31886861 DOI: 10.1093/ehjcvp/pvz081] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/20/2019] [Accepted: 12/07/2019] [Indexed: 12/18/2022]
Abstract
AIMS We hypothesized that adherence to statin therapy determines survival in patients with peripheral artery disease (PAD). METHODS AND RESULTS Single-centre longitudinal observational study with 691 symptomatic PAD patients. Mortality was evaluated over a mean follow-up of 50 ± 26 months. We related statin adherence and low-density lipoprotein cholesterol (LDL-C) target attainment to all-cause mortality. Initially, 73% of our PAD patients were on statins. At follow-up, we observed an increase to 81% (P < 0.0001). Statin dosage, normalized to simvastatin 40 mg, increased from 50 to 58 mg/day (P < 0.0001), and was paralleled by a mean decrease of LDL-C from 97 to 82 mg/dL (P < 0.0001). The proportion of patients receiving a high-intensity statin increased over time from 38% to 62% (P < 0.0001). Patients never receiving statins had a significant higher mortality rate (31%) than patients continuously on statins (13%) or having newly received a statin (8%; P < 0.0001). Moreover, patients on intensified statin medication had a low mortality of 9%. Those who terminated statin medication or reduced statin dosage had a higher mortality (34% and 20%, respectively; P < 0.0001). Multivariate analysis showed that adherence to or an increase of the statin dosage (both P = 0.001), as well as a newly prescribed statin therapy (P = 0.004) independently predicted reduced mortality. CONCLUSION Our data suggest that adherence to statin therapy is associated with reduced mortality in symptomatic PAD patients. A strategy of intensive and sustained statin therapy is recommended.
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Affiliation(s)
- Jörn F Dopheide
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Jonas Veit
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Hana Ramadani
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Luise Adam
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.,Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Lucija Papac
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Alexander Vonbank
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
| | - Mathias Kaspar
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Aljoscha Rastan
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Iris Baumgartner
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Heinz Drexel
- Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.,Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.,Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.,Drexel University College of Medicine, Philadelphia, PA, USA
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15
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Abstract
There is now overwhelming evidence to support lowering LDL-c (low-density lipoprotein cholesterol) to reduce cardiovascular morbidity and mortality. Statins are a class of drugs frequently prescribed to lower cholesterol. However, in spite of their wide-spread use, discontinuation and nonadherence remains a major gap in both the primary and secondary prevention of atherosclerotic cardiovascular disease. The major reason for statin discontinuation is because of the development of statin-associated muscle symptoms, but a range of other statin-induced side effects also exist. Although the mechanisms behind these side effects have not been fully elucidated, there is an urgent need to identify those at increased risk of developing side effects as well as provide alternative treatment strategies. In this article, we review the mechanisms and clinical importance of statin toxicity and focus on the evaluation and management of statin-associated muscle symptoms.
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Affiliation(s)
- Natalie C Ward
- From the School of Public Health, Curtin University, Perth, Western Australia, Australia (N.C.W.).,School of Medicine, University of Western Australia, Perth, Australia (N.C.W., G.F.W.)
| | - Gerald F Watts
- School of Medicine, University of Western Australia, Perth, Australia (N.C.W., G.F.W.).,Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Western Australia, Australia (G.F.W.)
| | - Robert H Eckel
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora (R.H.E.)
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16
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Ward NC, Page MM, Watts GF. Clinical guidance on the contemporary use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies. Diabetes Obes Metab 2019; 21 Suppl 1:52-62. [PMID: 31002454 DOI: 10.1111/dom.13637] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 01/09/2019] [Accepted: 01/10/2019] [Indexed: 12/01/2022]
Abstract
There is now significant evidence for the benefits of lowering low-density lipoprotein cholesterol (LDL-c) to reduce the risk of atherosclerotic cardiovascular disease (ASCVD). Although statins are the most widely prescribed lipid-lowering therapy that effectively lower LDL-c, especially in combination with ezetimibe, some patients require adjunctive therapy to further lower LDL-c and mitigate attendant risk of ASCVD. The gap can be filled by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies whose use is currently supported by two recent cardiovascular outcome studies and new treatment guidelines. We provide an overview of extant studies investigating PCSK9 monoclonal antibodies in various patient populations, an update of the guidelines regarding their use and a case-based discussion.
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Affiliation(s)
- Natalie C Ward
- School of Public Health, Curtin University, Perth, Australia
- School of Medicine, University of Western Australia, Perth, Australia
| | - Michael M Page
- School of Medicine, University of Western Australia, Perth, Australia
- PathWest Laboratory Medicine, Fiona Stanley Hospital, Perth, Australia
| | - Gerald F Watts
- School of Medicine, University of Western Australia, Perth, Australia
- Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia
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Mefford MT, Tajeu GS, Tanner RM, Colantonio LD, Monda KL, Dent R, Farkouh ME, Rosenson RS, Safford MM, Muntner P. Willingness to be Reinitiated on a Statin (from the REasons for Geographic and Racial Differences in Stroke Study). Am J Cardiol 2018; 122:768-774. [PMID: 30057227 DOI: 10.1016/j.amjcard.2018.05.016] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 05/14/2018] [Accepted: 05/18/2018] [Indexed: 10/14/2022]
Abstract
Guidelines recommend attempting to reinitiate statins in patients who discontinue treatment. Previous experiences while taking a statin, including side effects, may reduce a patient's willingness to reinitiate treatment. We determined the percentage of adults who are willing to reinitiate statin therapy after treatment discontinuation. Factors associated with willingness to reinitiate a statin were also examined. A statin questionnaire was administered and study examination conducted in black and white US adults enrolled in the nationwide REasons for Geographic And Racial Differences in Stroke study from 2013 to 2017. In participants who self-reported ever having taken a statin (n = 7,216, mean age 72 years, 53% women, 34% black), 1,081 (15%) reported having discontinued treatment. Among those who discontinued treatment, statin side effects, perceived lack of need for a statin, and cost were reported by 66%, 31%, and 3% of participants, respectively. Overall, 37% of participants who had discontinued treatment were willing to reinitiate statin therapy. Participants who discontinued treatment due to cost (prevalence ratio [PR] 1.61; 95% confidence interval (CI) 1.01, 2.57) were more likely to report a willingness to reinitiate therapy. Participants with a low-density lipoprotein-cholesterol ≥130 mg/dl versus <100 mg/dl (PR 0.69; 95% CI 0.53, 0. 88) and who discontinued treatment due to side effects (PR 0.51; 95% CI 0.41, 0.64) were less likely to report willingness to reinitiate statin therapy. In conclusion, a substantial proportion of participants who discontinued statin therapy were willing to reinitiate treatment. Healthcare providers should discuss reinitiation of statin therapy with their patients who have discontinued treatment.
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Kim S, Kim H, Kim E, Han S, Rane PP, Fox KM, Zhao Z, Qian Y, Suh HS. Utilization Patterns of Lipid-lowering Therapies in Patients With Atherosclerotic Cardiovascular Disease or Diabetes: A Population-based Study in South Korea. Clin Ther 2018; 40:940-951.e7. [PMID: 29735297 DOI: 10.1016/j.clinthera.2018.04.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 04/11/2018] [Accepted: 04/11/2018] [Indexed: 11/20/2022]
Abstract
PURPOSE We aimed to study the utilization patterns of lipid-lowering treatment (LLT), including treatment modification, adherence, and possible statin intolerance, in patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes using national claims data in South Korea. METHODS A retrospective cohort study was conducted using data from the Korean Health Insurance Review & Assessment Service claims database. Patients aged ≥18 years with >1 outpatient pharmacy claim for a statin and/or ezetimibe dated January 1, 2012, to December 31, 2014, were identified and categorized into the following cohorts: patients with ASCVD, and patients with diabetes mellitus without ASCVD. LLT modification, adherence to index LLT, and possible statin intolerance were explored during the 12 months after the date of first prescription for a statin and/or ezetimibe. FINDINGS Among 1,399,872 patients who met the eligibility criteria, 807,547 (57.7%) were patients with ASCVD and 592,325 (42.3%) were patients with diabetes without ASCVD. About half of the patients had no modification in their index treatment (46.2% in the ASCVD cohort and 48.9% in the diabetes cohort), and the most common modification was permanent discontinuation (19.6% in the ASCVD cohort and 21.4% in the diabetes cohort). The mean medication possession ratios were 0.77 in the ASCVD cohort and 0.73 in the diabetes cohort and showed a decreasing trend during the 12-month follow-up period. Among patients who initiated a statin and/or ezetimibe, possible statin intolerance was observed in 53,921 patients (6.7%) in the ASCVD cohort and 42,172 patients (7.1%) in the diabetes cohort. IMPLICATIONS In South Korea, a high rate of permanent discontinuation of statin therapy in patients with ASCVD or diabetes places these patients at high risk for cardiovascular events in the future. A decreasing trend of adherence to LLT implies that more intensive education and management are required to improve therapeutic effect and reduce the risk for ASCVD. The high rate of possible statin intolerance highlights an unmet need in the prevention and management of ASCVD in South Korea.
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Affiliation(s)
- Siin Kim
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Hyungtae Kim
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Eunju Kim
- College of Pharmacy, Pusan National University, Busan, South Korea
| | - Sola Han
- College of Pharmacy, Pusan National University, Busan, South Korea
| | | | - Kathleen M Fox
- Strategic Healthcare Solutions, LLC, Aiken, South Carolina
| | | | - Yi Qian
- Amgen, Inc, Thousand Oaks, California
| | - Hae Sun Suh
- College of Pharmacy, Pusan National University, Busan, South Korea.
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Aguilar-Palacio I, Malo S, Feja C, Lallana M, León-Latre M, Casasnovas JA, Rabanaque M, Guallar E. Risk factors control for primary prevention of cardiovascular disease in men: Evidence from the Aragon Workers Health Study (AWHS). PLoS One 2018; 13:e0193541. [PMID: 29474499 PMCID: PMC5825136 DOI: 10.1371/journal.pone.0193541] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 02/13/2018] [Indexed: 11/19/2022] Open
Abstract
Benefits of cardiovascular disease (CVD) risk factors control are well known, but goals achievement remains low. The objective of this study is to evaluate the prevalence of CVD risk factors among men ina worker's cohort with no previous CVD, to study control variations across time and the factors associated with poor control. To this end, we conducted a cohort reexamination (2010-2014) within the context of the Aragon Workers Health Study (AWHS). Data from working characteristics, analytical values and pharmacological prescription were included in the analysis. Prevalences of risk factor diagnosis and control were calculated, as well as factors associated with poor control. The prevalence of CVD risk factors was high. In 2014dyslipidaemia was the most prevalent (85.2%) followed by Hypertension (HT) (42.0%). People under treatment increased for the period analysed (p<0.001). The proportion of people treated varied from 72.2% in Diabetes Mellitus to 31.1% in dyslipidaemia in 2014. 46.2% of the workers with HT were controlled, decreasing to 21.9% in Diabetes and 11.0% in dyslipidaemia (2014). Working in a turn different to central shift was associated with poor control, especially for those working at night with HT (Odds Ratio in 2010: 3.6; Confidence Interval 95% 1.8-7.4) and dyslipidaemia (Odds Ratio 2010: 4.7; Confidence Interval 95% 1.3-16.4). We conclude that, although CVD control has increased significantly for the period studied, there are still many people that do not receive any treatment, and control goals are normally not achieved.
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Affiliation(s)
- Isabel Aguilar-Palacio
- Preventive Medicine and Public Health Department, Zaragoza University, Zaragoza, Spain
- Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
- * E-mail:
| | - Sara Malo
- Preventive Medicine and Public Health Department, Zaragoza University, Zaragoza, Spain
- Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
| | - Cristina Feja
- Preventive Medicine and Public Health Department, Zaragoza University, Zaragoza, Spain
- Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
| | - MªJesús Lallana
- Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
- Primary Health Care, Servicio Aragonés de Salud, Zaragoza, Spain
| | | | - José Antonio Casasnovas
- Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
- Medicine, Psychiatry and Dermatology Department, Zaragoza University, Zaragoza, Spain
| | - MªJosé Rabanaque
- Preventive Medicine and Public Health Department, Zaragoza University, Zaragoza, Spain
- Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
| | - Eliseo Guallar
- Epidemiology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America
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Martin-Ruiz E, Olry-de-Labry-Lima A, Ocaña-Riola R, Epstein D. Systematic Review of the Effect of Adherence to Statin Treatment on Critical Cardiovascular Events and Mortality in Primary Prevention. J Cardiovasc Pharmacol Ther 2018; 23:200-215. [DOI: 10.1177/1074248417745357] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Eva Martin-Ruiz
- Escuela Andaluza de Salud Pública (EASP), Campus Universitario de Cartuja, Granada, Spain
| | - Antonio Olry-de-Labry-Lima
- Escuela Andaluza de Salud Pública (EASP), Campus Universitario de Cartuja, Granada, Spain
- CIBER en Epidemiología y Salud Pública (CIBERESP), Spain
- Instituto de Investigación Biosanitaria ibs, Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
| | - Ricardo Ocaña-Riola
- Escuela Andaluza de Salud Pública (EASP), Campus Universitario de Cartuja, Granada, Spain
- Instituto de Investigación Biosanitaria ibs, Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
| | - David Epstein
- Facultad de Ciencias Económicas, Universidad de Granada, Campus Universitario de Cartuja, Granada, Spain
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Corrao G, Monzio Compagnoni M, Franchi M, Cantarutti A, Pugni P, Merlino L, Catapano AL, Mancia G. Good adherence to therapy with statins reduces the risk of adverse clinical outcomes even among very elderly. Evidence from an Italian real-life investigation. Eur J Intern Med 2018; 47:25-31. [PMID: 28958460 DOI: 10.1016/j.ejim.2017.09.023] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 08/31/2017] [Accepted: 09/21/2017] [Indexed: 12/17/2022]
Abstract
AIM To assess whether in individuals aged 80years or older adherence to statins is accompanied by a reduced risk of all-cause mortality and major cardiovascular events. METHODS A nested case-control study was carried out on a cohort of patients aged 80years or older (very elderly individuals), who were under treatment with statins between 2008 and 2009, using the database available for all citizenship (about 10 million) of Lombardy (Italy). Cases were the cohort members who experienced death or hospitalization for stroke, myocardial infarction or heart failure from the initial prescription until 2012. Up to five controls were randomly selected for each case. Logistic regression was used to model the outcome risk associated with the adherence to therapy with statins. Two younger patient cohorts aged 60 to 69years and 70 to 79years were taken for comparison. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty. RESULTS Among very elderly individuals, those who had high adherence to statins showed significant risk reductions of death (56%; 95% Confidence Interval, 54% to 59%), myocardial infarction (15%; 5% to 24%), stroke (13%; 0% to 24%) and heart failure (30%; 23% to 36%) with respect to those at very low adherence. Adherence-related risk reductions were only slightly better for younger cohort members. CONCLUSIONS Adherence to therapy with statins reduced the risk of both death and cardiovascular morbidity in patients aged 80years or older.
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Affiliation(s)
- Giovanni Corrao
- Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy.
| | - Matteo Monzio Compagnoni
- Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy
| | - Matteo Franchi
- Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy
| | - Anna Cantarutti
- Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy
| | - Pietro Pugni
- Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy
| | - Luca Merlino
- Operative Unit of Territorial Health Services, Lombardy Region, Milan, Italy
| | - Alberico L Catapano
- Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, Italy; IRCSS Multimedica, Sesto San Giovanni, Milan, Italy
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22
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Raebel MA, Dyer W, Nichols GA, Goodrich GK, Schmittdiel JA. Relationships between Medication Adherence and Cardiovascular Disease Risk Factor Control in Elderly Patients with Diabetes. Pharmacotherapy 2017; 37:1204-1214. [PMID: 28752555 PMCID: PMC5647232 DOI: 10.1002/phar.1994] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
BACKGROUND The Centers for Medicare and Medicaid Services (CMS) Medicare Star program provides incentives to health plans when their patients with diabetes meet adherence targets to angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) and statins. While a link between adherence and cardiovascular risk factor control is established, most studies included young patients with few comorbidities. Whether the Star adherence target is associated with reduced blood pressure or low-density lipoprotein cholesterol (LDL-C) in complex older patients is not well understood. OBJECTIVES Determine correlates of adherence and examine the effect of meeting Star adherence targets on blood pressure and LDL-C in the Medicare-aged diabetes population. DESIGN AND SUBJECTS Retrospective cohort study of 129,040 patients with diabetes aged 65 or older. MEASURES Adherence estimated using proportion of days covered target ≥ 0.8; blood pressure < 140/90 mg Hg; LDL-C < 100 mg/dl. Modified Poisson regression used to assess relationships. RESULTS Adherence differed little across elderly age groups. Compared to no comorbidity, high comorbidity (≥ 4) was associated with lower ACEI/ARB (risk ratio [RR] 0.88 [95% confidence interval (CI) 0.87-0.89]) or statin (RR 0.91 [0.90-0.92]) adherence. ACEI/ARB adherence was not associated with blood pressure < 140/90 mm Hg in patients ≥ 85 years (RR 1.01 [0.96-1.07]) or with multiple comorbidities (e.g., 3: RR 1.04 [0.99-1.08]). Statin adherence and LDL-C < 100 mg/dl were associated in all elderly age groups (e.g., ≥ 85: RR 1.13 [1.09-1.16]) and comorbidity levels (e.g., ≥ 4: RR 1.13 [1.12-1.15]). CONCLUSIONS Adherence to ACEI/ARB is not linked with reduced blood pressure in patients with diabetes who are at least 85 years or with multiple comorbidities.
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Affiliation(s)
- Marsha A. Raebel
- Kaiser Permanente Colorado Institute for Health Research, Denver, Colorado, USA
- University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA
| | - Wendy Dyer
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Gregory A. Nichols
- Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, USA
| | - Glenn K. Goodrich
- Kaiser Permanente Colorado Institute for Health Research, Denver, Colorado, USA
| | - Julie A. Schmittdiel
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
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Deshpande S, Quek RGW, Forbes CA, de Kock S, Kleijnen J, Gandra SR, Simpson RJ. A systematic review to assess adherence and persistence with statins. Curr Med Res Opin 2017; 33:769-778. [PMID: 28076703 DOI: 10.1080/03007995.2017.1281109] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
OBJECTIVE To identify and assess studies published over a 10 year period up to February 2016 which measure adherence or persistence with statins, to summarize their methods, strengths and weaknesses and to summarize evidence linking statin adherence/persistence with risk of cardiovascular events. METHODS Electronic databases and abstracts from four major cardiovascular disease conferences were searched from January 2005 to February 2016. The study selection process was performed by two reviewers working independently. Studies were included if they reported data regarding patient adherence or persistence with statins in adults with primary hypercholesterolemia, using any type of study design or length of follow-up. One reviewer extracted the study data and assessed study quality, which was checked by a second reviewer independently. Given the heterogeneity between the included studies a narrative critique and summary is presented. RESULTS We report on 84 real world studies which aimed to assess adherence or persistence with statins. The majority of studies concluded that good adherence/persistence was associated with reduction in cardiovascular events and mortality. In two studies high intensity statin regimens were associated with poorer patient adherence when compared to low intensity statins. Adherence and persistence with statin therapy also has an impact on hospitalization costs and other cardiovascular disease (CVD) related costs. CONCLUSIONS Adherence and persistence are associated with a reduction in CVD events and mortality. There was limited evidence to suggest that high intensity statin regimens are associated with poorer treatment adherence when compared to lower intensity regimens. Hence, more robust studies are required to establish this association. As recommended by the 2013 ACC/AHA, 2016 ESC and several other clinical guidelines, clinicians and pharmacy managers should regularly monitor statin therapy adherence.
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Affiliation(s)
| | - Ruben G W Quek
- b Amgen Inc., One Amgen Center Drive , Thousand Oaks , CA , USA
| | - Carol A Forbes
- a Kleijnen Systematic Reviews Ltd , York , United Kingdom
| | | | - Jos Kleijnen
- a Kleijnen Systematic Reviews Ltd , York , United Kingdom
- c School for Public Health and Primary Care , Maastricht University , Maastricht , The Netherlands
| | | | - Ross J Simpson
- d UNC Hospitals Heart and Vascular Center at Meadowmont , Chapel Hill , NC , USA
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24
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Abstract
The use of low-density lipoprotein cholesterol (LDL-C)-lowering medications has led to a significant reduction of cardiovascular risk in both primary and secondary prevention. Statin therapy, one of the cornerstones for the prevention and treatment of cardiovascular disease (CVD), has been demonstrated to be effective in lowering LDL-C levels and in reducing the risk for CVD and is generally well-tolerated. However, compliance with statins remains suboptimal. One of the main reasons is limitations by adverse events, notably myopathies, which can lead to non-compliance with the prescribed statin regimen. Reducing the burden of elevated LDL-C levels is critical in patients with CVD as well as in patients with very high baseline levels of LDL-C (e.g. patients with familial hypercholesterolaemia), as statin therapy is insufficient for optimally reducing LDL-C below target values. In this review, we discuss alternative treatment options after maximally tolerated doses of statin therapy, including ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and cholesteryl ester transfer protein (CETP) inhibitors. Difficult-to-treat patients may benefit from combination therapy with ezetimibe or a PCSK9 inhibitor (evolocumab or alirocumab, which are now available). Updates of treatment guidelines are needed to guide the management of patients who will best benefit from these new treatments.
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Affiliation(s)
- Stephan Krähenbühl
- Division of Clinical Pharmacology and Toxicology, University Hospital, Basel, Switzerland
- Department of Clinical Research, University of Basel, Basel, Switzerland
| | | | - Arnold von Eckardstein
- Institute of Clinical Chemistry, University Hospital Zürich, Zurich, Switzerland
- Zürich Center for Integrative Human Physiology, University of Zürich, Zurich, Switzerland
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Banach M, Stulc T, Dent R, Toth PP. Statin non-adherence and residual cardiovascular risk: There is need for substantial improvement. Int J Cardiol 2016; 225:184-196. [PMID: 27728862 DOI: 10.1016/j.ijcard.2016.09.075] [Citation(s) in RCA: 142] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Accepted: 09/23/2016] [Indexed: 12/18/2022]
Abstract
Although statin therapy has proven to be the cornerstone for prevention and treatment of cardiovascular disease (CVD), there are many patients for whom long-term therapy remains suboptimal. The aims of this article are to review the current complex issues associated with statin use and to explore when novel treatment approaches should be considered. Statin discontinuation as well as adherence to statin therapy remain two of the greatest challenges for lipidologists. Evidence suggests that between 40 and 75% of patients discontinue their statin therapy within one year after initiation. Furthermore, whilst the reasons for persistence with statin therapy are complex, evidence shows that low-adherence to statins negatively impacts clinical outcomes and residual CV risk remains a major concern. Non-adherence or lack of persistence with long-term statin therapy in real-life may be the main cause of inadequate low density lipoprotein cholesterol lowering with statins. There is a large need for the improvement of the use of statins, which have good safety profiles and are inexpensive. On the other hand, in a non-cost-constrained environment, proprotein convertase subtilisin/kexin type 9 inhibitors should arguably be used more often in those patients in whom treatment with statins remains unsatisfactory.
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Affiliation(s)
- Maciej Banach
- Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland; Healthy Aging Research Centre, Medical University of Lodz, Lodz, Poland; Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
| | - Tomas Stulc
- 3rd Department of Internal Medicine, 1st University of Medicine, Prague, Czech Republic
| | | | - Peter P Toth
- CGH Medical Center, Sterling, IL, USA; Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Bellows BK, Olsen CJ, Voelker J, Wander C. Antihyperlipidemic Medication Treatment Patterns and Statin Adherence Among Patients with ASCVD in a Managed Care Plan After Release of the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol. J Manag Care Spec Pharm 2016; 22:892-900. [PMID: 27459651 PMCID: PMC10397611 DOI: 10.18553/jmcp.2016.22.8.892] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND The American College of Cardiology (ACC) and American Heart Association (AHA) released a new blood cholesterol treatment guideline in November 2013. It is unknown how the new recommendations have affected cholesterol medication use and adherence in a commercial health plan. OBJECTIVE To evaluate the effect of the 2013 guideline release on antihyperlipidemic treatment patterns and statin adherence in patients with atherosclerotic cardiovascular disease (ASCVD) compared with a historical control group. METHODS This study was a historical cohort analysis of adult patients (aged 21-75 years) with clinical ASCVD enrolled in a SelectHealth commercial health plan. Patients were included in the guideline implementation cohort if they had a medical claim with an ICD-9-CM diagnosis of ASCVD in the year before the November 2013 ACC/AHA guideline release. The index date was defined as the first outpatient medical claim with an ICD-9-CM for ASCVD in the first 6 months after the guideline was released. Patients were required to have continuous enrollment for ≥ 1 year before and after the index date. These same criteria were applied to patients exactly 4 years earlier to identify a historical control group. Patients meeting these criteria formed the antihyperlipidemic treatment patterns cohort. Of these, patients who also had ≥1 pharmacy claim for a statin in the 1-year pre- and post-index periods were included in the statin adherence cohort. Antihyperlipidemic treatment patterns were assessed using pharmacy claims for antihyperlipidemic medications in the 1-year pre- and post-index periods. Antihyperlipidemic medication claims were classified as a nonstatin cholesterol medication, low-intensity statin, moderate-intensity statin, or high-intensity statin. To address differences in pre-index antihyperlipidemic medications between the guideline implementation and historical control groups, patients were randomly matched 1:1 based on pre-index classification in a post hoc analysis. Post-index antihyperlipidemic classifications were compared between groups using a Stuart-Maxwell test. The change in mean statin adherence (proportion of days covered [PDC]) was compared within and between groups using paired and independent t-tests, respectively. The proportion of adherent patients (PDC ≥ 0.80) in the pre- and post-index periods was compared between groups using a chi-square test. A multivariable logistic regression was used to compare the likelihood of being adherent in the post-index period while controlling for pre-index adherence and other potential confounders. RESULTS A total of 7,818 adult members with ASCVD in the index period and 1 year before the index period were identified. Of those, 1,841 patients met the criteria to be included in the analysis, and 1,526 patients were matched on antihyperlipidemic classification and included in the antihyperlipidemic treatment patterns analysis. Baseline characteristics were similar, although the guideline implementation group was younger (58.3 vs. 60.5 years, P < 0.001), and more were male (74.8% vs. 71.3%, P = 0.106) than the historical control group. In the matched cohort, there was a significant difference in the post-index antihyperlipidemic classification (P < 0.001), which appeared to be a result of the difference in nonstatin cholesterol medications (guideline 6.9% vs. historical 13.0%) and high-intensity statins (guideline 23.7% vs. historical 16.3%). Of the 1,841 patients in the antihyperlipidemic treatment patterns cohort, 919 patients met inclusion criteria for the statin adherence analysis. Although PDC decreased over time in both groups, significantly more patients in the guideline implementation group were adherent in the post-index period than the historical control group (66.5% vs. 57.3%, respectively; P = 0.005). Additionally, patients in the guideline implementation group were more likely than the historical control to be adherent in the post-index period when adjusting for potential confounders (OR = 1.49, 95% CI = 1.10-2.03; P = 0.011). CONCLUSIONS Since the release of the updated ACC/AHA treatment guideline, more commercial health plan patients with ASCVD used high-intensity statins and fewer used nonstatin cholesterol medications than historical controls. Additionally, since the guideline release, more patients are adherent to statin therapy than historical controls. This study provides managed care organizations with valuable information regarding the effect of the 2013 ACC/AHA guideline. DISCLOSURES No outside funding or services were received for this work. Outside of the current study, Bellows has received research funding from Biogen Idec, Regeneron Pharmaceuticals, Myriad Genetic Laboratories, Shire Development, and Bristol-Myers Squibb and an honorariam from Avanir Pharmaceuticals. Voelker received summer intern support from Pfizer and the AMCP Foundation during the time of this study. The remaining authors have nothing to disclose. All authors contributed to study concept and design and to the revision of the manuscript. Bellows, Olsen, and Voelker collected the data, assisted by Wander; data interpretation was performed primarily by Bellows, along with Olsen and Voelker and assisted by Wander. The manuscript was primarily written by Bellows, along with the other authors.
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Luebke T, Brunkwall J. Development of a Microsimulation Model to Predict Stroke and Long-Term Mortality in Adherent and Nonadherent Medically Managed and Surgically Treated Octogenarians with Asymptomatic Significant Carotid Artery Stenosis. World Neurosurg 2016; 92:513-520.e2. [DOI: 10.1016/j.wneu.2016.05.034] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 05/15/2016] [Accepted: 05/17/2016] [Indexed: 11/30/2022]
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Lavikainen P, Helin-Salmivaara A, Eerola M, Fang G, Hartikainen J, Huupponen R, Korhonen MJ. Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence. BMJ Open 2016; 6:e011306. [PMID: 27259530 PMCID: PMC4893857 DOI: 10.1136/bmjopen-2016-011306] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVES Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. DESIGN Retrospective cohort study. SETTING Finnish healthcare registers. PARTICIPANTS Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). OUTCOMES Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. RESULTS During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). CONCLUSIONS Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect.
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Affiliation(s)
- Piia Lavikainen
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
- Drug Research Doctoral Programme, University of Turku, Turku, Finland
| | - Arja Helin-Salmivaara
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
- Unit of Primary Health Care, Hospital District of Helsinki and Uusimaa, Helsinki, Finland
| | - Mervi Eerola
- The Center of Statistics, University of Turku, Turku, Finland
| | - Gang Fang
- Division of Pharmaceutical Outcomes and Policy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Juha Hartikainen
- Heart Center, Kuopio University Hospital, Kuopio, Finland
- School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Risto Huupponen
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
- Department of Clinical Pharmacology, Tykslab, Turku University Hospital, Turku, Finland
| | - Maarit Jaana Korhonen
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
- Division of Pharmaceutical Outcomes and Policy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA
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McKenzie SJ, McLaughlin D, Clark J, Doi SAR. The burden of non-adherence to cardiovascular medications among the aging population in Australia: a meta-analysis. Drugs Aging 2016; 32:217-25. [PMID: 25749743 DOI: 10.1007/s40266-015-0245-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Non-adherence to cardiovascular medications is a problem worldwide, even in Australia, which has a socialized medical system, Medicare. OBJECTIVE The aim of this systematic review was to evaluate the burden of non-adherence to cardiovascular medications and factors thereof in Australia. DATA SOURCES Pubmed, Embase, CINAHL, PsycInfo, Cochrane Library databases were searched. ELIGIBILITY CRITERIA Articles were included if they were in English, peer-reviewed and provided empirical data on adherence to cardiovascular medication for an Australian cohort. METHODS A meta-analysis of prevalence of medication non-adherence using the double arcsine square root transformed proportion was undertaken. Studies were pooled in homogenous prevalence groups and factors that differed across groups were ascertained. RESULTS Five studies, including eight datasets and 76,867 subjects were analyzed. Three more or less homogenous prevalence categories were discernable: low [19 %, 95 % confidence interval (CI) 15-24], moderate (26 %, 95 % CI 23-29) and high (43 %, 95 % CI 43-44; this was a single study) prevalence of non-adherence. There were minimal clear patterns across groups in relation to typical factors of non-adherence (patient, condition, healthcare system or socioeconomic factors). Measurements used for non-adherence were similar for six of the eight included datasets, suggesting this did not affect prevalence of non-adherence or inclusion in a prevalence group. CONCLUSIONS Non-adherence to cardiovascular medications is a serious problem in the aging Australian setting with an overall prevalence of between 14 and 43 %. The lack of patterns in the typical factors of non-adherence suggests that another factor, such as patients' beliefs about their conditions and medications, may be playing a stronger role in their non-adherence than clinical or sociodemographic factors. This is an area for further research.
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Affiliation(s)
- Samantha J McKenzie
- The University of Queensland, School of Population Health, Herston Road, Herston, Brisbane, QLD, 4006, Australia,
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Lyons I, Barber N, Raynor DK, Wei L. The Medicines Advice Service Evaluation (MASE): a randomised controlled trial of a pharmacist-led telephone based intervention designed to improve medication adherence. BMJ Qual Saf 2016; 25:759-69. [PMID: 26755665 DOI: 10.1136/bmjqs-2015-004670] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 12/09/2015] [Indexed: 11/03/2022]
Abstract
AIM To test the effectiveness of a tailored, pharmacist-led centralised advice service to improve adherence to patients on established medications. METHODS A parallel group randomised controlled trial was conducted. Patients prescribed at least one oral medication for type 2 diabetes and/or lipid regulation were eligible to participate. 677 patients of a mail-order pharmacy were recruited and randomised (340 intervention, 337 control). The intervention comprised two tailored telephone consultations with a pharmacist, 4-6 weeks apart, plus a written summary of the discussion and a medicines reminder chart. The primary outcome was self-reported adherence to medication at 6-month follow-up, collected via a postal questionnaire, analysed using generalised estimating equations. Secondary outcomes included prescription refill adherence, lipid and glycaemic control and patient satisfaction. RESULTS In intention-to-treat analysis 36/340 (10.6%) of the intervention group were non-adherent (<90% of medication taken in the past 7 days) at 6 months compared with 66/337 (19.6%) in the control group, yielding an unadjusted OR of 1.54 (95% CI 1.11 to 2.15, p=0.01). Analyses of dispensing data also showed that the odds of being classified as adherent (≥90%) were 60% greater for the intervention group compared with the control group (OR 1.60, 95% CI 1.14 to 2.24, p<0.01). In a subsample of patients who provided blood samples, glycaemic and lipid control did not differ significantly between groups (p=0.06 and p=0.24, respectively) but positive trends were observed. Ninety-two per cent of intervention group patients reported that they were satisfied with the service overall. CONCLUSIONS A telephone intervention, led by a pharmacist and tailored to the individuals' needs, can significantly improve medication adherence in patients with long-term conditions, using a mail-order pharmacy. Further work is needed to confirm a trend towards improved clinical outcome. TRIAL REGISTRATION NUMBER NCT01864239.
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Affiliation(s)
- Imogen Lyons
- UCL Interaction Centre, University College London, London, UK
| | | | | | - Li Wei
- Research Department of Practice and Policy, UCL School of Pharmacy, University College London, London, UK
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Izadpanah R, Schächtele DJ, Pfnür AB, Lin D, Slakey DP, Kadowitz PJ, Alt EU. The impact of statins on biological characteristics of stem cells provides a novel explanation for their pleiotropic beneficial and adverse clinical effects. Am J Physiol Cell Physiol 2015. [DOI: 10.1152/ajpcell.00406.2014] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Statins reduce atherosclerotic events and cardiovascular mortality. Their side effects include memory loss, myopathy, cataract formation, and increased risk of diabetes. As cardiovascular mortality relates to plaque instability, which depends on the integrity of the fibrous cap, we hypothesize that the inhibition of the potential of mesenchymal stem cells (MSCs) to differentiate into macrophages would help to explain the long known, but less understood “non-lipid-associated” or pleiotropic benefit of statins on cardiovascular mortality. In the present investigation, MSCs were treated with atorvastatin or pravastatin at clinically relevant concentrations and their proliferation, differentiation potential, and gene expression profile were assessed. Both types of statins reduced the overall growth rate of MSCs. Especially, statins reduced the potential of MSCs to differentiate into macrophages while they exhibited no direct effect on macrophage function. These findings suggest that the limited capacity of MSCs to differentiate into macrophages could possibly result in decreased macrophage density within the arterial plaque, reduced inflammation, and subsequently enhance plaque stability. This would explain the non-lipid-associated reduction in cardiovascular events. On a negative side, statins impaired the osteogenic and chondrogenic differentiation potential of MSCs and increased cell senescence and apoptosis, as indicated by upregulation of p16, p53 and Caspase 3, 8, and 9. Statins also impaired the expression of DNA repair genes, including XRCC4, XRCC6, and Apex1. While the effect on macrophage differentiation explains the beneficial side of statins, their impact on other biologic properties of stem cells provides a novel explanation for their adverse clinical effects.
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Affiliation(s)
- Reza Izadpanah
- Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana
- Department of Surgery, Tulane University Health Sciences Center, New Orleans, Louisiana; and
| | - Deborah J. Schächtele
- Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana
| | - Andreas B. Pfnür
- Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana
| | - Dong Lin
- Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana
| | - Douglas P. Slakey
- Department of Surgery, Tulane University Health Sciences Center, New Orleans, Louisiana; and
| | - Philip J. Kadowitz
- Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana
| | - Eckhard U. Alt
- Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana
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Rannanheimo PK, Tiittanen P, Hartikainen J, Helin-Salmivaara A, Huupponen R, Vahtera J, Korhonen MJ. Impact of Statin Adherence on Cardiovascular Morbidity and All-Cause Mortality in the Primary Prevention of Cardiovascular Disease: A Population-Based Cohort Study in Finland. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2015; 18:896-905. [PMID: 26409618 DOI: 10.1016/j.jval.2015.06.002] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 03/15/2015] [Accepted: 06/07/2015] [Indexed: 06/05/2023]
Abstract
OBJECTIVES To assess the extent to which adherence to statins is associated with the incidence of cardiovascular (CV) events and all-cause mortality in the primary prevention of CV diseases and whether different analytical approaches influence the observed associations. METHODS This population-based cohort study used data from Finnish registers. The cohort included 97,575 new statin users aged 45 to 75 years in 2001 to 2004 with no CV diseases at baseline. Exposure was defined as adherence to statins (proportion of days covered [PDC]). The primary outcome was any CV event or death during a 3-year follow-up. Different analytical approaches, including multivariable-adjusted Cox regression, inverse probability weighting with time-varying adherence, and propensity score calibration, were used. RESULTS During the first year of follow-up, 53% displayed good (PDC ≥80%), 26% had intermediate (PDC 40%-79%), and 21% exhibited poor (PDC <40%) adherence. After adjustment for sociodemographic and clinical covariates, a 25% relative risk reduction (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.79) was observed in the rate of any CV event or death among good versus poor adherers. Good adherers also had a lower incidence than poor adherers of acute coronary syndrome (HR 0.56; 95% CI 0.49-0.65) and acute cerebrovascular disease events (HR 0.67; 95% CI 0.60-0.76). The different analytical approaches achieved comparable results for all the outcomes. CONCLUSIONS The incidence of CV events and mortality was higher in poor versus good adherers. Different analytical methods that took into account changes in adherence and confounding at baseline did not appreciably affect the results.
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Affiliation(s)
- Piia K Rannanheimo
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland; Finnish Medicines Agency, Kuopio, Finland
| | - Pekka Tiittanen
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
| | - Juha Hartikainen
- Heart Center, Kuopio University Hospital, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Arja Helin-Salmivaara
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
| | - Risto Huupponen
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland; Clinical Pharmacology Unit, Tykslab, Turku University Hospital, Turku, Finland
| | - Jussi Vahtera
- Department of Public Health, University of Turku, Turku, Finland
| | - Maarit Jaana Korhonen
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
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Qiu Q, Duan XW, Li Y, Yang LK, Chen Y, Li H, Duan ZP, Wang L. Impact of partial reimbursement on hepatitis B antiviral utilization and adherence. World J Gastroenterol 2015; 21:9588-9597. [PMID: 26327766 PMCID: PMC4548119 DOI: 10.3748/wjg.v21.i32.9588] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 04/28/2015] [Accepted: 06/15/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the impact of partial reimbursement for antivirals on antiviral utilization and adherence for chronic hepatitis B patients. METHODS This was a retrospective cohort study. Two separate cohorts were enrolled, including 14163 and 16288 chronic hepatitis B outpatients, respectively. These patients were referred to Beijing You'an Hospital before and after the new partial reimbursement for antivirals, which was implemented on July 1, 2011. Demographic characteristics (including medical insurance status), routine biochemical, virological and serology laboratory test results, and antiviral agents' prescription information were collected from an electronic database. Patients were also defined as new and existing patients according to treatment history. Antiviral utilization, medication possession ratio and persistence rate were calculated and compared among the patients with different characteristics. A questionnaire survey was conducted among 212 randomly sampled outpatients from the same hospital to confirm the validity of the electronic database. Propensity score matching was used to adjust the distribution of patient's characteristics which may influence the antiviral utilization. χ(2) test or ANOVA was adopted and multivariate logistic regression was used to determine the factors associated with antiviral utilization and good adherence. RESULTS A total of 13364 outpatients from each cohort were enrolled after the propensity score matching. The antiviral utilization rate for the insured patients increased from 57.4% to 75.9% (P < 0.0001) after the reimbursement, and the rate among those who paid out-of-pocket increased from 54.9% to 56.7% (P = 0.028). Approximately 71% of the patients had a medication possession ratio of more than 80% in each cohort before reimbursement. This increased to 79.2% and 73.1% for insured patients and those who paid out-of-pocket, respectively (P < 0.0001). Insured patients and those who paid out-of-pocket had the similar persistence rates before reimbursement. But after reimbursement, insured patients had higher persistence rates than those who paid out-of-pocket at 6 (86.5% vs 81.5%, P < 0.0001), 9 (79.7% vs 69.9%, P < 0.0001), 12 (73.4% vs 61.9%, P < 0.0001), and 15 mo (66.6% vs 53.1%, P < 0.0001). The reimbursement could significantly improve adherence for the insured patients than those who paid out-of-pocket even after adjusting other covariates, with an interaction odds ratio of 1.422 (95%CI: 1.220-1.657, P < 0.0001). The questionnaire survey supported the validity of the electronic database. CONCLUSION The reimbursement policy shows a positive impact on antiviral utilization as well as adherence for insured chronic hepatitis B patients.
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Birtcher K. When compliance is an issue-how to enhance statin adherence and address adverse effects. Curr Atheroscler Rep 2015; 17:471. [PMID: 25410047 DOI: 10.1007/s11883-014-0471-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Cardiovascular disease is prevalent and costly. Interventions and therapies that reduce morbidity and mortality associated with cardiovascular disease could have an enormous impact on clinical and economic outcomes. Statins reduce atherosclerotic cardiovascular disease-related morbidity and mortality; however, adherence to statins is less than optimal. It is important for clinicians as well as health plan managers to be aware of the patient- and insurance plan-specific factors that have been shown to influence adherence. Perceived statin-related side effects may also decrease adherence. Statin-related myalgia may be difficult to distinguish from myalgia caused by other conditions, and statin therapy may be discontinued unnecessarily in patients who would otherwise benefit. It is imperative that clinicians work closely with patients to improve adherence to statin therapy and be knowledgable in managing potential statin-related side effects.
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Affiliation(s)
- Kim Birtcher
- University of Houston College of Pharmacy, 1441 Moursund St., Houston, TX, 77030, USA,
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De Vera MA, Bhole V, Burns LC, Lacaille D. Impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review. Br J Clin Pharmacol 2015; 78:684-98. [PMID: 25364801 DOI: 10.1111/bcp.12339] [Citation(s) in RCA: 213] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
AIMS While suboptimal adherence to statin medication has been quantified in real-world patient settings, a better understanding of its impact is needed, particularly with respect to distinct problems of medication taking. Our aim was to synthesize current evidence on the impacts of statin adherence, discontinuation and persistence on cardiovascular disease and mortality outcomes. METHODS We conducted a systematic review of peer-reviewed studies using a mapped search of Medline, Embase and International Pharmaceutical Abstracts databases. Observational studies that met the following criteria were included: defined patient population;statin adherence exposure; defined study outcome [i.e. cardiovascular disease (CVD), mortality]; and reporting of statin-specific results. RESULTS Overall, 28 studies were included, with 19 studies evaluating outcomes associated with statin adherence, six with statin discontinuation and three with statin persistence. Among adherence studies, the proportion of days covered was the most widely used measure, with the majority of studies reporting increased risk of CVD (statistically significant risk estimates ranging from 1.22 to 5.26)and mortality (statistically significant risk estimates ranging from 1.25 to 2.54) among non-adherent individuals. There was greater methodological variability in discontinuation and persistence studies. However, findings of increased CVD (statistically significant risk estimates ranging from 1.22 to 1.67) and mortality (statistically significant risk estimates ranging from 1.79 to 5.00) among nonpersistent individuals were also consistently reported. CONCLUSIONS Observational studies consistently report an increased risk of adverse outcomes associated with poor statin adherence. These findings have important implications for patients and physicians and emphasize the importance of monitoring and encouraging adherence to statin therapy.
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van Breukelen-van der Stoep DF, Zijlmans J, van Zeben D, Klop B, van de Geijn GJM, van der Meulen N, Hazes M, Birnie E, Castro Cabezas M. Adherence to cardiovascular prevention strategies in patients with rheumatoid arthritis. Scand J Rheumatol 2015; 44:443-8. [PMID: 26169960 DOI: 10.3109/03009742.2015.1028997] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVES Patients with rheumatoid arthritis (RA) have a high risk of cardiovascular disease (CVD). Recent national and international guidelines suggest strict treatment of CVD risk factors in RA. The aim of this study was to evaluate the self-reported adherence to CV prevention strategies in patients with RA. METHOD RA patients visiting an outpatient clinic for strict CVD risk management received a validated questionnaire to evaluate adherence to CV prevention strategies. Strict treatment targets were defined and lifestyle recommendations were given following a prespecified protocol. CVD risk was assessed using the SCORE algorithm. RESULTS In total, 111 questionnaires were returned (response rate of 82%). A high 10-year CVD risk (≥ 20%) was present in 53%, but only 3% thought they had an increased CVD risk. A total of 53% of patients reported that they 'follow the doctors' suggestions exactly' and 75% reported finding it 'easy to follow the suggestions'. Of the 69% of patients who were prescribed lipid- and/or blood pressure-lowering drugs, 90% reported taking all prescribed tablets. The advice to follow a diet was given to 42%, of whom 68% said they followed the advised diet. Physical exercise was advised to 67%, of whom 62% said they performed specific physical exercise on at least 3 days a week. The adherence to lifestyle recommendations was not significantly different across the CVD risk groups. CONCLUSIONS RA patients tend to underestimate their CVD risk. The self-reported adherence of RA patients to CVD risk management was high concerning pharmaceutical interventions and moderate in the case of lifestyle interventions.
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Affiliation(s)
| | - J Zijlmans
- a Department of Rheumatology , Sint Franciscus Gasthuis , Rotterdam , The Netherlands
| | - D van Zeben
- a Department of Rheumatology , Sint Franciscus Gasthuis , Rotterdam , The Netherlands
| | - B Klop
- b Department of Internal Medicine , Sint Franciscus Gasthuis , Rotterdam , The Netherlands
| | - G J M van de Geijn
- c Department of Clinical Chemistry , Sint Franciscus Gasthuis , Rotterdam , The Netherlands
| | - N van der Meulen
- b Department of Internal Medicine , Sint Franciscus Gasthuis , Rotterdam , The Netherlands
| | - M Hazes
- d Department of Rheumatology , Erasmus Medical Centre , Rotterdam , The Netherlands
| | - E Birnie
- e Institute of Health Policy and Management , Erasmus University , Rotterdam , The Netherlands.,f Statistics and Education , Sint Franciscus Gasthuis , Rotterdam , The Netherlands
| | - M Castro Cabezas
- b Department of Internal Medicine , Sint Franciscus Gasthuis , Rotterdam , The Netherlands
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Cho EJ, Moon KJ. Related factors of medication adherence in patients with dyslipidemia: The 2010-2012 Korean National Health and Nutrition Examination Survey. ACTA ACUST UNITED AC 2015. [DOI: 10.14367/kjhep.2015.32.2.65] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Kypridemos C, Bandosz P, Hickey GL, Guzman-Castillo M, Allen K, Buchan I, Capewell S, O’Flaherty M. Quantifying the contribution of statins to the decline in population mean cholesterol by socioeconomic group in England 1991 - 2012: a modelling study. PLoS One 2015; 10:e0123112. [PMID: 25856394 PMCID: PMC4391910 DOI: 10.1371/journal.pone.0123112] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 02/27/2015] [Indexed: 01/22/2023] Open
Abstract
Background Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statins are effective for cholesterol control in individual patients. At the population level, however, their contribution to total cholesterol decline remains unclear. The aim of this study was to quantify the contribution of statins to the observed fall in population mean cholesterol levels in England over the past two decades, and explore any differences between socioeconomic groups. Methods and Findings This is a modelling study based on data from the Health Survey for England. We analysed changes in observed mean total cholesterol levels in the adult England population between 1991-92 (baseline) and 2011-12. We then compared the observed changes with a counterfactual ‘no statins’ scenario, where the impact of statins on population total cholesterol was estimated and removed. We estimated uncertainty intervals (UI) using Monte Carlo simulation, where confidence intervals (CI) were impractical. In 2011-12, 13.2% (95% CI: 12.5-14.0%) of the English adult population used statins at least once per week, compared with 1991-92 when the proportion was just 0.5% (95% CI: 0.3-1.0%). Between 1991-92 and 2011-12, mean total cholesterol declined from 5.86 mmol/L (95% CI: 5.82-5.90) to 5.17 mmol/L (95% CI: 5.14-5.20). For 2011-12, mean total cholesterol was lower in more deprived groups. In our ‘no statins’ scenario we predicted a mean total cholesterol of 5.36 mmol/L (95% CI: 5.33-5.40) for 2011-12. Statins were responsible for approximately 33.7% (95% UI: 28.9-38.8%) of the total cholesterol reduction since 1991-92. The statin contribution to cholesterol reduction was greater among the more deprived groups of women, while showing little socio-economic gradient among men. Conclusions Our model suggests that statins explained around a third of the substantial falls in total cholesterol observed in England since 1991. Approximately two thirds of the cholesterol decrease can reasonably be attributed non-pharmacological determinants.
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Affiliation(s)
- Chris Kypridemos
- Department of Public Health and Policy, University of Liverpool, Liverpool, United Kingdom
- * E-mail:
| | - Piotr Bandosz
- Department of Public Health and Policy, University of Liverpool, Liverpool, United Kingdom
- Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland
| | - Graeme L. Hickey
- Epidemiology and Population Health Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom
| | - Maria Guzman-Castillo
- Department of Public Health and Policy, University of Liverpool, Liverpool, United Kingdom
| | - Kirk Allen
- Department of Public Health and Policy, University of Liverpool, Liverpool, United Kingdom
- Lancaster Medical School, Lancaster University, Lancaster, United Kingdom
| | - Iain Buchan
- Centre for Health Informatics, Institute of Population Health, University of Manchester, Manchester, United Kingdom
| | - Simon Capewell
- Department of Public Health and Policy, University of Liverpool, Liverpool, United Kingdom
| | - Martin O’Flaherty
- Department of Public Health and Policy, University of Liverpool, Liverpool, United Kingdom
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Turin A, Pandit J, Stone NJ. Statins and Nonadherence. J Cardiovasc Pharmacol Ther 2015; 20:447-56. [DOI: 10.1177/1074248415578170] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Accepted: 02/23/2015] [Indexed: 12/18/2022]
Abstract
Statin nonadherence is a major challenge to optimal management. Patients nonadherent to statin therapy do not receive the expected benefit relative to the degree of low-density lipoprotein cholesterol (LDL-C) lowering obtained. This is important because new evidence guidelines recommend statins as the first-line therapy for those in high-risk groups (secondary prevention, patients with diabetes 40-75 years of age, and LDL-C ≥ 190 mg/dL) and in selected primary prevention patients. Statin assignment in the latter group occurs only in those with an estimated ≥7.5% 10-year atherosclerotic cardiovascular disease risk after shared decision making in a clinician–patient risk discussion. However, in numerous studies, statin nonadherence shows little or no benefit in reducing cardiovascular events or mortality compared to placebo, effectively negating the risk reduction expected from statin use and concomitantly increasing the total cost of health care. The causes and solutions for nonadherence are multifactorial and include patient, clinician, and health system factors. We believe that a clinician–patient partnership that facilitates patients’ understanding of the potential for optimal benefit with the least adverse effects is an important first step toward improving adherence. A transtheoretical model of stages of behavior change helps clinicians address many of the common factors limiting adherence to statins. We conclude with a teaching tool emphasizing a structured approach to statin therapy with patient-centered risk discussions.
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Affiliation(s)
- Alexander Turin
- Department of Internal Medicine, Loyola University Medical Center, Maywood, IL, USA
| | - Jay Pandit
- Department of Cardiology, Bluhm Cardiovascular Institute, Northwestern University, Chicago, IL, USA
| | - Neil J. Stone
- Department of Cardiology, Bluhm Cardiovascular Institute, Northwestern University, Chicago, IL, USA
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Long-term statin treatment in children with familial hypercholesterolemia: more insight into tolerability and adherence. Paediatr Drugs 2015; 17:159-66. [PMID: 25644328 PMCID: PMC4372689 DOI: 10.1007/s40272-014-0116-y] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Statins are currently the preferred pharmacological therapy in individuals with familial hypercholesterolemia (FH) with the aim to prevent premature atherosclerosis. In adults, these agents have been proven to be safe and well tolerated; however, non-adherence is a significant clinical issue. OBJECTIVES In this study, we evaluated tolerability and adherence to statin therapy in young adult FH patients 10 years after this was initiated in their childhood. METHODS A questionnaire including items on medical history, adherence and reasons for discontinuation was sent to 214 young adult FH patients that initiated statin therapy at least 10 years ago. Tolerability was defined as 100% minus the percentage of patients that discontinued statin therapy due to side effects. Adherence was defined as the extent to which patients took their medication as prescribed by their physician. We labelled patients adherent if they took 80% or more of their pills in the month preceding our assessment. RESULTS Follow-up was successful in 205 (95.8%) subjects (age 18-30 years). A history of side effects was reported by 40 (19.5%) of the patients, and mainly consisted of muscle complaints and gastrointestinal symptoms. Three patients (1.5%) discontinued statin therapy because of side effects. Rhadbomyolysis or other serious adverse events were not reported. In fact, 169 (82.4%) of 205 patients remained on statin treatment and 78.7% (148 out of 188) were adherent. None of the patient characteristics were significantly associated with adherence. CONCLUSIONS Individuals with FH who started statin therapy in childhood demonstrated good adherence during ten years of treatment. Furthermore, statin therapy was well tolerated; only a small minority discontinued therapy because of side effects and the side effects that were reported were mild in nature.
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Watanabe JH, Ney JP. Association of increased emergency rooms costs for patients without access to necessary medications. Res Social Adm Pharm 2014; 11:499-506. [PMID: 25487421 DOI: 10.1016/j.sapharm.2014.10.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2014] [Revised: 10/15/2014] [Accepted: 10/15/2014] [Indexed: 11/27/2022]
Abstract
BACKGROUND Prescription medications are an important component of chronic disease management. They are vital in preventing unnecessary ER visits. However, few studies have examined the association between patients' self-reported inability to receive necessary medications and emergency room costs. OBJECTIVES The study objectives were to: 1) determine differences in ER costs based on self-reported ability to obtain necessary medications. 2) identify differences in ER costs based on self-reported ability to obtain necessary medications among medication users. The association was also examined by insurance category. METHODS Respondent data from 10 years (2002-2011) of the U.S. Medical Expenditure Panel Survey was analyzed. The models employed estimated the association of respondents reporting being 'unable to receive necessary medications' on ER expenditures. Secondarily, the relationship was assessed by insurance category: private, public, and uninsured. Two-part cost regression models with bootstrapped estimates to produce 95% confidence intervals of cost differences were applied for these analyses. Significance was set at α = 0.05. Analyses were completed using SAS 9.4 (Cary, NC) and Stata 13 (College Station, TX). Estimates were in 2011 US dollars. RESULTS People unable to receive necessary medications experienced increased average annual ER costs of $46.62 with 95% a confidence interval [CI] of 34.76-58.49) compared to patients able to receive necessary medications. By insurance category, respondents unable to receive necessary medications experienced increased ER costs of $104.80 (95% CI: 60.57-149.03), $42.16 (95% CI: 24.65-59.68), and $33.18 (95% CI: 18.54-47.82), for Publically Insured, Privately Insured, and Uninsured, respectively. Findings were similar for those already using medications. CONCLUSIONS Inability to obtain necessary medications is associated with increased emergency room costs. Those with public insurance have a larger increase in ER costs if they are without necessary medications compared to those insured privately or without insurance.
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Affiliation(s)
- Jonathan Hirohiko Watanabe
- University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, 9500 Gilman Drive, La Jolla, CA 92093-0714, USA.
| | - John P Ney
- University of Washington, Comparative Effectiveness, Cost and Outcomes Research Center, Box 359736, PSB Suite 5076, 325 Ninth Ave, Seattle, WA 98104, USA
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Slejko JF, Sullivan PW, Anderson HD, Ho PM, Nair KV, Campbell JD. Dynamic medication adherence modeling in primary prevention of cardiovascular disease: a Markov microsimulation methods application. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2014; 17:725-731. [PMID: 25236996 DOI: 10.1016/j.jval.2014.06.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Revised: 06/02/2014] [Accepted: 06/14/2014] [Indexed: 06/03/2023]
Abstract
BACKGROUND Real-world patients' medication adherence is lower than that of clinical trial patients. Hence, the effectiveness of medications in routine practice may differ. OBJECTIVES The study objective was to compare the outcomes of an adherence-naive versus a dynamic adherence modeling framework using the case of statins for the primary prevention of cardiovascular (CV) disease. METHODS Statin adherence was categorized into three state-transition groups on the basis of an epidemiological cohort study. Yearly adherence transitions were incorporated into a Markov microsimulation using TreeAge software. Tracker variables were used to store adherence transitions, which were used to adjust probabilities of CV events over the patient's lifetime. Microsimulation loops "random walks" estimated the average accrued quality-adjusted life-years (QALYs) and CV events. For each 1,000-patient microsimulations, 10,000 outer loops were performed to reflect second-order uncertainty. RESULTS The adherence-naive model estimated 0.14 CV events avoided per person, whereas the dynamic adherence model estimated 0.08 CV events avoided per person. Using the adherence-naive model, we found that statin therapy resulted in 0.40 QALYs gained over the lifetime horizon on average per person while the dynamic adherence model estimated 0.22 incremental QALYs gained. Subgroup analysis revealed that maintaining high adherence in year 2 resulted in 0.23 incremental QALYs gained as compared with 0.16 incremental QALYs gained when adherence dropped to the lowest level. CONCLUSIONS A dynamic adherence Markov microsimulation model reveals risk reduction and effectiveness that are lower than with an adherence-naive model, and reflective of real-world practice. Such a model may highlight the value of improving or maintaining good adherence.
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Affiliation(s)
- Julia F Slejko
- Pharmaceutical Outcomes Research and Policy Program, University of Washington School of Pharmacy, Seattle, WA.
| | | | - Heather D Anderson
- University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
| | - P Michael Ho
- VA Eastern Colorado Health Care System, University of Colorado, Denver CO
| | - Kavita V Nair
- University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
| | - Jonathan D Campbell
- University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
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Galema-Boers JMH, Lenzen MJ, van Domburg RT, Roeters van Lennep J, van Bruchem-van de Scheur GG, Sijbrands EJ, Langendonk JG. Predicting non-adherence in patients with familial hypercholesterolemia. Eur J Clin Pharmacol 2014; 70:391-7. [DOI: 10.1007/s00228-013-1640-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Accepted: 12/29/2013] [Indexed: 11/24/2022]
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Abstract
Abstract
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45
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Wallach-Kildemoes H, Andersen M, Diderichsen F, Lange T. Adherence to preventive statin therapy according to socioeconomic position. Eur J Clin Pharmacol 2013; 69:1553-63. [PMID: 23588558 DOI: 10.1007/s00228-013-1488-6] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2012] [Accepted: 02/19/2013] [Indexed: 10/27/2022]
Abstract
AIM To explore whether long-term adherence to preventive statin therapy depends on socioeconomic position (SEP). METHODS A cohort of individuals without established cardiovascular disease (CVD) or diabetes initiating preventive statin therapy during 2002-2005 was followed in the individual-level Danish registries for 4 years or until censoring events (death, emigration, CVD or diabetes). Only individuals aged 40-84 years for whom information was available on the SEP indicators, education and income were included (N = 76,038). Two different aspects of poor adherence were applied as outcome measures: (1) Proportion of days covered (PDC) with medication below 80 %, assuming a daily dose of one tablet (continuity); (2) Discontinuation defined as a gap between two consecutive prescriptions exceeding 365 days (persistence). Stratum-specific logistic regression analyses were applied to estimate the odds ratio (OR) for PDC <80 % across SEP, adjusting for age and hypertension. Hazard ratio (HR) for discontinuation was estimated by Cox regression analyses. RESULTS Adjusting mutually for income and education, the OR for PDC <80 % decreased with increasing income. Comparing the highest income quintile with the lowest, the OR were 0.64 (95 % Confidence Interval 0.64-0.65) and 0.73 (0.73-0.74) in men aged 40-64 and 65-84 years, respectively; in women, the figures were 0.79 (0.79-0.79) and 0.95 (0.94-0.95), respectively. While observed increases in adherence with longer education in unadjusted analyses were attenuated after adjustment for income among men, the potential inverse relationship between length of education and adherence was enhanced among women. Applying discontinuation as outcome, analogous differences were demonstrated. CONCLUSION Adherence to preventive statin therapy in Denmark decreases with decreasing income-especially in men aged 40-64 years.
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Affiliation(s)
- Helle Wallach-Kildemoes
- Section for Health Service Research, Centre for Healthy Ageing, Faculty of Health and Medical Science, University of Copenhagen, CSS, Øster Farimagsgade 5, 1014 Copenhagen, Denmark.
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Bitton A, Choudhry NK, Matlin OS, Swanton K, Shrank WH. The impact of medication adherence on coronary artery disease costs and outcomes: a systematic review. Am J Med 2013; 126:357.e7-357.e27. [PMID: 23507208 DOI: 10.1016/j.amjmed.2012.09.004] [Citation(s) in RCA: 150] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2012] [Revised: 08/31/2012] [Accepted: 09/04/2012] [Indexed: 11/29/2022]
Abstract
BACKGROUND Given the huge burden of coronary artery disease and the effectiveness of medication therapy, understanding and quantifying known impacts of poor medication adherence for primary and secondary prevention is crucial. We sought to systematically review the literature on this topic area with a focus on quantified cost and clinical outcomes related to adherence. METHODS We conducted a systematic review of the literature between 1966 and November 2011 using a fixed search strategy, multiple reviewers, and a quality rating scale. We found 2636 articles using this strategy, eventually weaning them down to 25 studies that met our inclusion criteria. Three reviewers independently reviewed the studies and scored them for quality using the Newcastle Ottawa Scoring Scale. RESULTS We found 5 studies (4 of which focused on statins) that measured the impact of medication adherence on primary prevention of coronary artery disease and 20 articles that focused on the relationship between medication adherence to costs and outcomes related to secondary prevention of coronary artery disease. Most of these latter studies focused on antihypertensive medications and aspirin. All controlled for confounding comorbidities and sociodemographic characteristics, but few controlled for likelihood of adherent patients to have healthier behaviors ("healthy adherer effect"). Three studies found that high adherence significantly improves health outcomes and reduces annual costs for secondary prevention of coronary artery disease (between $294 and $868 per patient, equating to 10.1%-17.8% cost reductions between high- and low-adherence groups). The studies were all of generally of high quality on the Newcastle Ottawa Scale (median score 8 of 9). CONCLUSIONS Increased medication adherence is associated with improved outcomes and reduced costs, but most studies do not control for a "healthy adherer" effect.
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Affiliation(s)
- Asaf Bitton
- Division of General Medicine, Brigham and Women's Hospital, Boston, MA 02120, USA.
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Proportion and Risk Indicators of Nonadherence to Statin Therapy: A Meta-analysis. Can J Cardiol 2012; 28:574-80. [DOI: 10.1016/j.cjca.2012.05.007] [Citation(s) in RCA: 134] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2012] [Revised: 05/18/2012] [Accepted: 05/18/2012] [Indexed: 11/30/2022] Open
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Chotiyaputta W, Hongthanakorn C, Oberhelman K, Fontana RJ, Licari T, Lok ASF. Adherence to nucleos(t)ide analogues for chronic hepatitis B in clinical practice and correlation with virological breakthroughs. J Viral Hepat 2012; 19:205-12. [PMID: 22329375 DOI: 10.1111/j.1365-2893.2011.01494.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Medication adherence is important for the success of nucleos(t)ide analogue (NUC) treatment for chronic hepatitis B. The aims of this study were to determine adherence to NUCs and factors associated with NUC adherence and to correlate NUC adherence with the occurrence of virological breakthroughs in patients with chronic hepatitis B. Consecutive patients with chronic hepatitis B receiving NUC were asked to complete a survey every 3 months. Adherence was also assessed by healthcare providers in the clinic. Adherence rate was defined as the per cent of days the patients took their hepatitis B virus medications during the last 30 days. A total of 111 patients were studied. The mean age was 47.7 years, 73.9% were men, 57.7% were Asian, 42.3% had postgraduate education and 80% had private insurance. Sixty-nine (74.1%) patients reported 100% adherence in the survey, while 78 (83.9%) reported 100% adherence to their healthcare providers. Patients with 100% adherence based on the survey were older (P = 0.02), more likely to be men (P = 0.006), and had higher annual household income (P = 0.04) than those with <100% adherence. In the 80 patients who completed three surveys, viral breakthrough was observed in 1/46 (2.2%) with 100% adherence on all three surveys, 1/18 (5.6%) with <100% adherence on one survey and 3/16 (18.8%) with <100% adherence on ≥2 surveys, (P = 0.06). In conclusion, adherence to NUC therapy in our patients with chronic hepatitis B was high but self-reporting of adherence to healthcare providers may be inflated. Patients with chronic hepatitis B with better adherence to NUC therapy had a trend towards a lower rate of viral breakthroughs.
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Affiliation(s)
- W Chotiyaputta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109, USA
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Evaluation of Cardiovascular Morbidity Associated with Adherence to Atorvastatin Therapy. Am J Ther 2012; 19:24-32. [DOI: 10.1097/mjt.0b013e3181ee707e] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Eaddy MT, Cook CL, O'Day K, Burch SP, Cantrell CR. How patient cost-sharing trends affect adherence and outcomes: a literature review. P & T : A PEER-REVIEWED JOURNAL FOR FORMULARY MANAGEMENT 2012; 37:45-55. [PMID: 22346336 PMCID: PMC3278192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Accepted: 08/12/2011] [Indexed: 05/31/2023]
Abstract
OBJECTIVE We sought to assess the relationship between patient cost sharing; medication adherence; and clinical, utilization, and economic outcomes. METHODOLOGY We conducted a literature review of articles and abstracts published from January 1974 to May 2008. Articles were identified using PubMed, Ovid, medline, Web of Science, and Google Scholar databases. The following terms were used in the search: adherence, compliance, copay, cost sharing, costs, noncompliance, outcomes, hospitalization, utilization, economics, income, and persistence. RESULTS We identified and included 160 articles in the review. Although the types of interventions, measures, and populations studied varied widely, we were able to identify relatively clear relationships between cost sharing, adherence, and outcomes. Of the articles that evaluated the relationship between changes in cost sharing and adherence, 85% showed that an increasing patient share of medication costs was significantly associated with a decrease in adherence. For articles that investigated the relationship between adherence and outcomes, the majority noted that increased adherence was associated with a statistically significant improvement in outcomes. CONCLUSION Increasing patient cost sharing was associated with declines in medication adherence, which in turn was associated with poorer health outcomes.
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