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Abidor E, Achkar M, Al Saidi I, Lather T, Jdaidani J, Agarwal A, El-Sayegh S. Comprehensive Review of Lipid Management in Chronic Kidney Disease and Hemodialysis Patients: Conventional Approaches, and Challenges for Cardiovascular Risk Reduction. J Clin Med 2025; 14:643. [PMID: 39860649 PMCID: PMC11765848 DOI: 10.3390/jcm14020643] [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: 12/09/2024] [Revised: 01/12/2025] [Accepted: 01/14/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Lipid disorders are very prevalent in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), leading to heightened cardiovascular risk. This review examines the effectiveness of lipid-lowering agents in these populations and explores gaps in the current research. The goal of this review is to assess the efficacy of lipid-lowering therapies in CKD and ESRD patients and identify future research needs. It aims to provide a clearer understanding of how these treatments impact cardiovascular risk in high-risk populations. Methods: We conducted a literature search in Embase, PubMed, Cochrane, and Google Scholar databases using keywords including but not limited to: chronic kidney diseases, dialysis, hemodialysis, dyslipidemia, statins, ezetimibe, and lipid-lowering drugs. Findings from included studies were synthetized to provide an overview of the current management of dyslipidemia in ESRD and HD. Results: Statins show mixed results in CKD and ESRD, with limited benefits in reducing cardiovascular events in dialysis patients. Agents like PCSK9 inhibitors show promising results but require further research, while non-statin therapies like fibrates and omega-3 fatty acids have limited evidence for use in this population. Conclusions: The review underscores the need for further research into lipid-lowering agents in CKD and ESRD patients, highlighting the need for tailored lipid management strategies in vulnerable patients with unique risk factors. More studies are needed to refine treatment strategies and assess the role of exercise and accurate risk calculators in managing cardiovascular outcomes.
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Affiliation(s)
- Erica Abidor
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Michel Achkar
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Ibrahim Al Saidi
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Tanvi Lather
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Jennifer Jdaidani
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Alaukika Agarwal
- Department of Medicine, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA; (E.A.); (M.A.); (I.A.S.); (T.L.); (J.J.); (A.A.)
| | - Suzanne El-Sayegh
- Department of Medicine, Division of Nephrology, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA
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Wang Z, Zhang P, Tian J, Zhang P, Yang K, Li L. Statins for the primary prevention of venous thromboembolism. Cochrane Database Syst Rev 2024; 11:CD014769. [PMID: 39498835 PMCID: PMC11536507 DOI: 10.1002/14651858.cd014769.pub2] [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] [Indexed: 11/07/2024]
Abstract
BACKGROUND Venous thromboembolism (VTE) involves the formation of a blood clot in a vein, and includes deep venous thrombosis (DVT) or pulmonary embolism (PE). The annual incidence for VTE varies from 0.75 to 2.69 per 1000 individuals, with about 40 million people worldwide impacted by VTE. Statins, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors, inhibit cholesterol biosynthesis and display several vascular-protective effects, including antithrombotic properties. However, the potential role of statins in the primary prevention of VTE is still not clear. OBJECTIVES To evaluate the benefits and risks of statins in preventing venous thromboembolism (VTE) in individuals with no prior history of VTE. SEARCH METHODS We used standard Cochrane search methods. The search was last updated on 13 March 2023. SELECTION CRITERIA We included randomized controlled trials (RCTs) comparing statins with any control intervention (including placebo and usual care) in healthy individuals or participants with conditions other than VTE. There were no restrictions on the dose, duration, route, or timing of statins. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were VTE, DVT, and PE. Our secondary outcomes were serious adverse events, adverse events, and mortality. We used the trial sequential analysis (TSA) method to judge whether the evidence was sufficient, and we used the GRADE approach to assess the certainty of the evidence for each outcome. MAIN RESULTS We included 27 RCTs involving 122,601 adults (aged 18 years and above) who were healthy, had various medical conditions (e.g. hypercholesterolemia), or were at risk for cardiovascular disease. Both males and females were included in all studies. Two studies focused solely on participants over 60 years of age. We deemed four studies to have a low risk of bias overall, while 19 were at high risk of bias, and four were unclear. The 27 studies compared use of statins versus placebo or usual care in individuals who had never experienced VTE. The statins used in the studies were atorvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, and simvastatin. Twenty-three studies followed up participants for over a year, with six of those extending follow-ups for over five years. Twenty-five studies were based in hospitals, and 24 studies were funded by industry. Only one study used VTE as a primary endpoint. The median incidence of VTE in the statins group was 0.72% (ranging from 0% to 10.53%), and in the control group it was 0.89% (ranging from 0% to 6.83%). Our pooled analysis of the 27 studies showed that, relative to control groups, statins may slightly reduce the overall incidence of VTE (odds ratio (OR) 0.86, 95% confidence intervals (CI) 0.76 to 0.98; 27 studies, 122,601 participants; low-certainty evidence). Of the statins we evaluated, only rosuvastatin seemed to be associated with a reduced incidence of VTE, albeit the reduction in incidence was very small. The evidence did not clearly indicate a difference between groups in the incidence of DVT (OR 0.70, 95% CI 0.41 to 1.18; six studies, 40,305 participants; low-certainty evidence), PE (OR 0.83, 95% CI 0.46 to 1.52; five studies, 28,427 participants; low-certainty evidence), or myopathy (OR 1.10, 95% CI 0.83 to 1.45; 10 studies, 75,551 participants; low-certainty evidence). Nonetheless, statin use might slightly decrease the incidence of any serious adverse event (OR 0.95, 95% CI 0.91 to 0.99; 13 studies, 67,020 participants; low-certainty evidence) and any death (OR 0.90, 95% CI 0.86 to 0.95; 24 studies, 116,761 participants; low-certainty evidence), compared to control. AUTHORS' CONCLUSIONS Using statins for the primary prevention of VTE may slightly reduce the incidence of VTE and all-cause mortality. However, this effect is likely too weak to be considered significant. Statin use may not decrease the occurrence of DVT and PE. The current evidence is insufficient to draw strong conclusions because of the risk of bias in the studies, imprecision in the effect estimates, and potential publication bias. More evidence from well conducted and fully reported RCTs is needed to assess the preventive effects of different types of statins, as well as the effects of different dosages and treatment durations in various populations.
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Affiliation(s)
- Zixin Wang
- Department of Breast Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Breast Disease, Hunan Province, Changsha, China
| | - Peng Zhang
- Department of Pediatric Surgery, The Second Hospital of Nanyang City, Nanyang, China
| | - Jinhui Tian
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou City, China
| | - Peizhen Zhang
- Maternity and Child-care, Hospital of Lanzhou City, Lanzhou City, China
| | - Kehu Yang
- Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou City, China
| | - Lun Li
- Department of Breast Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Breast Disease, Hunan Province, Changsha, China
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Dirjayanto VJ, Martin-Ruiz C, Pompei G, Rubino F, Kunadian V. The association of inflammatory biomarkers and long-term clinical outcomes in older adults with non-ST elevation acute coronary syndrome. Int J Cardiol 2024; 409:132177. [PMID: 38761976 DOI: 10.1016/j.ijcard.2024.132177] [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: 12/09/2023] [Revised: 04/28/2024] [Accepted: 05/13/2024] [Indexed: 05/20/2024]
Abstract
BACKGROUND The prognostic significance of inflammatory markers on the long-term risk of major adverse cardiovascular and cerebrovascular events (MACCE) in older NSTEACS patients remains unclear. METHODS NSTEACS patients aged 75 and older were recruited to the multicentre cohort study Improve Cardiovascular Outcomes in High-Risk PatieNts with Acute Coronary Syndrome (ICON1). Inflammatory markers including interleukin-6 (IL-6), myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), fibrinogen and tumor necrosis factor-alpha (TNF-α) were collected at baseline. Primary outcome was MACCE consisting of all-cause mortality, reinfarction, stroke/transient ischaemic attack, urgent revascularization, and significant bleeding at 5-year follow-up. RESULTS There were 230 patients with baseline IL-6 (median age 80.9 [interquartile range (IQR):78.2-83.9] years). High IL-6 was not associated with MACCE, but it was independently associated with all-cause mortality (adjusted hazard ratio [aHR]: 2.26 [95% Confidence Interval (CI):1.34-3.82]; P = 0.002). For patients with hsCRP (n = 260, median age 80.9 [IQR:77.9-84.1] years), higher levels were significantly associated with increased risk of MACCE (aHR:1.77 [95% CI:1.26-2.49], P = 0.001). In the cohort with MPO (230 patients, median age 80.9 [IQR:78.2-83.9] years), lower MPO was independently associated with the risk of MACCE (aHR: 0.67 [95%CI:0.46-0.96]; P = 0.029). There was no prognostic significance with fibrinogen and TNF-α. CONCLUSION Among older NSTEACS patients, elevated IL-6 and hsCRP were associated with increased risk of all-cause mortality and MACCE, respectively. Low MPO levels were associated with higher MACCE. Further studies are required to determine how these biomarkers should influence treatment strategy in this understudied subset. CLINICAL TRIAL REGISTRATION NCT01933581.
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Affiliation(s)
- Valerie Josephine Dirjayanto
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, United Kingdom; Faculty of Medicine, Universitas Indonesia, Indonesia
| | - Carmen Martin-Ruiz
- BioScreening Core Facility, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Graziella Pompei
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, United Kingdom; Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, FE, Italy
| | - Francesca Rubino
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, United Kingdom; Division of Cardiology, Department of Medicine, University of Verona, Verona, Italy
| | - Vijay Kunadian
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, United Kingdom; Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
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Mostaza JM, Escobar C. Rosuvastatin-Based Lipid-Lowering Therapy for the Control of LDL Cholesterol in Patients at High Vascular Risk. J Clin Med 2024; 13:1894. [PMID: 38610659 PMCID: PMC11012264 DOI: 10.3390/jcm13071894] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 03/15/2024] [Accepted: 03/19/2024] [Indexed: 04/14/2024] Open
Abstract
Vascular diseases are the leading cause of death in Spain. Hypercholesterolemia is not only a cardiovascular risk factor, but also underlies the etiopathogenesis of atherosclerosis. Therefore, reducing LDL cholesterol (LDL-C) to the goals recommended by clinical practice guidelines, is essential to decrease the risk of vascular complications. Despite this, current LDL-C control is scarce, even in subjects with high and very high risk. This is mainly due to an insufficient intensification of lipid-lowering treatment. In this context, it is essential to prescribe the appropriate therapy, adjusted to patient's needs based on their LDL-C and their vascular risk. Rosuvastatin, alone or in combination with ezetimibe, provides intensive LDL-C reductions (up to 50-55% and 60-75%, respectively), with a low risk of side effects and in an efficient manner, in patients both without and with established atherosclerotic vascular disease.
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Affiliation(s)
- Jose María Mostaza
- Lipid and Vascular Risk Unit, Department of Internal, University Hospital La Paz-Carlos III, 28046 Madrid, Spain;
| | - Carlos Escobar
- Cardiology Department, University Hospital La Paz-Carlos III, 28046 Madrid, Spain
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Barrios V, Escobar C. Fixed-dose combination of rosuvastatin and ezetimibe: treating hypercholesteremia according to cardiovascular risk. Expert Rev Clin Pharmacol 2021; 14:793-806. [PMID: 33970743 DOI: 10.1080/17512433.2021.1925539] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Introduction: Reducing low-density lipoprotein cholesterol (LDL-C) with lipid-lowering therapies has been associated with a decrease in the frequency of cardiovascular events.Areas covered: A systematic search was conducted on PubMed (MEDLINE), using the MeSH terms [Rosuvastatin] + [Ezetimibe] + [Dyslipidemia] + [treatment]. Original data from clinical trials, prospective and retrospective studies and more useful reviews were selected.Expert opinion: While statins continue to be the cornerstone of dyslipidemia management, many patients do not attain LDL-C targets with high-intensity statins alone. Rosuvastatin is a high-intensity statin with a low risk of adverse effects and drug-drug interactions and proven benefits in the prevention of cardiovascular disease. Rosuvastatin and ezetimibe have complementary mechanisms of action that enhance their ability to reduce LDL-C levels. Various studies have shown that the combination of rosuvastatin 10-40 mg and ezetimibe 10 mg enables considerable reductions in LDL-C (up to 60-75%) with a good safety profile in a broad spectrum of patients with hypercholesterolemia, including those at high risk and those with atherosclerotic cardiovascular disease. In addition, a fixed-dose combination of rosuvastatin and ezetimibe may improve adherence to medication. In this review, the available evidence on the combination of rosuvastatin and ezetimibe is updated.
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Affiliation(s)
- Vivencio Barrios
- Cardiology Department, University Hospital Ramón Y Cajal. Alcalá University, Madrid, Spain
| | - Carlos Escobar
- Cardiology Department, University Hospital La Paz, Madrid, Spain
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Azadnajafabad S, Karimian M, Roshani S, Rezaei N, Mohammadi E, Saeedi Moghaddam S, Ghasemi E, Sadeghi Morasa F, Rezaei N, Aminorroaya A, Ghanbari A, Nasserinejad M, Gorgani F, Larijani B, Farzadfar F. Population attributable fraction estimates of cardiovascular diseases in different levels of plasma total cholesterol in a large-scale cross-sectional study: a focus on prevention strategies and treatment coverage. J Diabetes Metab Disord 2020; 19:1453-1463. [PMID: 33520846 PMCID: PMC7843742 DOI: 10.1007/s40200-020-00673-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 10/26/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE Cardiovascular diseases (CVDs) are the main cause of deaths among non-communicable diseases. Arguments about the best prevention strategy to control CVDs' risk factors continue. We evaluated the population attributable fraction (PAF) of CVDs in different levels of plasma cholesterol. METHODS Patients' data were obtained from Iran STEPs 2016 study. In phase 0 we estimated PAF regardless of cholesterol levels and clinical factors. In phase 1 we calculated PAF based on three levels of cholesterol (<200, 200-240, ≥240 mg/dl). In phase 2 we estimated PAF in 3 groups considering lipid-lowering drugs. In phase 3 all treated participants and not treated hypercholesterolemic people were included, to evaluate the impact of treatment. Estimations were done for Ischemic heart disease (IHD) and ischemic stroke (IS), and for two sex. RESULTS In phase 0, the highest PAF for IHD and IS were 0.35 (95% confidence interval 0.29-0.41) and 0.22 (0.18-0.27) for females and 0.27 (0.22-0.32) and 0.18 (0.14-0.22) for males. In phase 1, the highest PAF belonged to population with cholesterol ≥240 mg/dl and IHD, as 0.90 (0.85-0.94) for females, and 0.90 (0.85-0.96) for males. In phase 2, the pre-hypercholesterolemic group had higher PAFs than the hypercholesteremic group in most of the population. Phase 3 showed treatment coverage significantly lowered fractions in all age groups, for both causes. CONCLUSION An urgent action plan and a change in preventive programs of health guidelines are needed to stop the vast burden of hypercholesterolemia in the pre-hypercholesterolemic population. Population-based prevention strategies need to be more considered to control further CVDs. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s40200-020-00673-3.
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Affiliation(s)
- Sina Azadnajafabad
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Maryam Karimian
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Third Floor, No.10, Jalal Al-e-Ahmad Highway, Tehran, Iran
| | - Shahin Roshani
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Negar Rezaei
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Esmaeil Mohammadi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Sahar Saeedi Moghaddam
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Erfan Ghasemi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Fatemeh Sadeghi Morasa
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Third Floor, No.10, Jalal Al-e-Ahmad Highway, Tehran, Iran
| | - Nazila Rezaei
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Arya Aminorroaya
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Ali Ghanbari
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Maryam Nasserinejad
- Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Fateme Gorgani
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Third Floor, No.10, Jalal Al-e-Ahmad Highway, Tehran, Iran
| | - Farshad Farzadfar
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 10, Al-e-Ahmad and Chamran Highway intersection, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Third Floor, No.10, Jalal Al-e-Ahmad Highway, Tehran, Iran
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Abstract
An increased risk of cardiovascular disease, independent of conventional risk factors, is present even at minor levels of renal impairment and is highest in patients with end-stage renal disease (ESRD) requiring dialysis. Renal dysfunction changes the level, composition and quality of blood lipids in favour of a more atherogenic profile. Patients with advanced chronic kidney disease (CKD) or ESRD have a characteristic lipid pattern of hypertriglyceridaemia and low HDL cholesterol levels but normal LDL cholesterol levels. In the general population, a clear relationship exists between LDL cholesterol and major atherosclerotic events. However, in patients with ESRD, LDL cholesterol shows a negative association with these outcomes at below average LDL cholesterol levels and a flat or weakly positive association with mortality at higher LDL cholesterol levels. Overall, the available data suggest that lowering of LDL cholesterol is beneficial for prevention of major atherosclerotic events in patients with CKD and in kidney transplant recipients but is not beneficial in patients requiring dialysis. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Lipid Management in CKD provides simple recommendations for the management of dyslipidaemia in patients with CKD and ESRD. However, emerging data and novel lipid-lowering therapies warrant some reappraisal of these recommendations.
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Kim K, Kwak A, Choi CU, Kim JH, Kim MG, Oh JM, Ji E. Differences in preventing new-onset cardiovascular events with statin therapy in seniors aged 75 years and over: A cohort study in the South Korean National Health Insurance Database. Basic Clin Pharmacol Toxicol 2019; 125:108-116. [PMID: 30924261 DOI: 10.1111/bcpt.13229] [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: 12/03/2018] [Accepted: 02/19/2019] [Indexed: 11/29/2022]
Abstract
The aim of this cohort study was to compare the effectiveness of statin regimens for primary prevention among seniors aged ≥ 75 years. Seniors aged 75-100 years for whom statin therapies for primary prevention were newly initiated between 1 January 2009 and 31 December 2011, and who continued the same statin regimen during the first year after the index date were identified using the claims data from the South Korean National Health Insurance Database. A propensity score matching and multivariable Cox proportional hazards model were developed to evaluate adjusted ischaemic cardiovascular-cerebrovascular event (CCE) risk and all-cause mortality risk for all patients, as well as for subgroups. A total of 5629 older patients aged 75-100 years were included in the study population. Compared to moderate-intensity statin therapy, low-intensity statin therapy was significantly associated with increased risk of ischaemic CCEs, while high-intensity statin therapy was associated with reduced risk of ischaemic CCEs; however, compared to moderate-intensity statin therapy, both low-intensity and high-intensity statin therapies were associated with increased risk of all-cause mortality. For the 4689 older patients who regularly received moderate-intensity statin therapy including 10 mg atorvastatin, 20 mg atorvastatin, 10 mg rosuvastatin or 20 mg simvastatin for primary prevention, multivariable regression adjusting for potential covariates revealed no significant difference in ischaemic CCEs or all-cause mortality between the moderate-intensity statin users and 10 mg atorvastatin users both before and after propensity scoring matching. No significant heterogeneity was detected in the patient subgroups. The results of this study based on real-world data can supply evidence-based reasons for choice of statin regimen for the primary prevention of CCEs in older people aged ≥ 75 years.
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Affiliation(s)
- Kyungim Kim
- College of Pharmacy, Korea University, Sejong, South Korea.,Biomedical Research Center, Korea University Guro Hospital, Seoul, South Korea
| | - Arim Kwak
- College of Pharmacy, Korea University, Sejong, South Korea
| | - Cheol Ung Choi
- Cardiovascular Center, Korea University Guro Hospital, Seoul, Korea
| | - Jae Hyun Kim
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea
| | - Myeong Gyu Kim
- Graduate School of Clinical Pharmacy, CHA University, Pocheon, South Korea
| | - Jung Mi Oh
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea
| | - Eunhee Ji
- College of Pharmacy, Gachon University, Incheon, South Korea
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Johns I, Moschonas KE, Medina J, Ossei-Gerning N, Kassianos G, Halcox JP. Risk classification in primary prevention of CVD according to QRISK2 and JBS3 'heart age', and prevalence of elevated high-sensitivity C reactive protein in the UK cohort of the EURIKA study. Open Heart 2018; 5:e000849. [PMID: 30564373 PMCID: PMC6269641 DOI: 10.1136/openhrt-2018-000849] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Revised: 08/02/2018] [Accepted: 08/31/2018] [Indexed: 01/08/2023] Open
Abstract
Objectives This study assessed cardiovascular disease (CVD) risk classification according to QRISK2, JBS3 'heart age' and the prevalence of elevated high-sensitivity C reactive protein (hsCRP) in UK primary prevention patients. Method The European Study on Cardiovascular Prevention and Management in Usual Daily Practice (EURIKA) (NCT00882336) was a cross-sectional study conducted in 12 European countries. 673 UK outpatients aged ≥50 years, without clinical CVD but with at least one conventional CVD risk factor, were recruited. 10-year CVD risk was calculated using QRISK2. JBS3 'heart age' and hsCRP level were assessed according to risk category. Results QRISK2 and JBS3 heart age was calculated for 285 of the 305 patients free from diabetes mellitus and not receiving a statin. QRISK2 classified 28%, 39% and 33% of patients as low (<10%), intermediate (10% to <20%) and high (≥20%) risk, respectively. Two-thirds of low-risk patients and half of intermediate-risk patients had a heart age ≥5 years and ≥10 years higher than their chronological age, respectively. Half of low-risk patients had hsCRP levels ≥2 mg/L and approximately 40% had levels ≥3 mg/L. Approximately 80% of low-risk patients had both elevated hsCRP and heart age relative to their chronological age. Conclusions Almost 40% more patients in this 'at risk' group would be eligible for statin therapy following the lowering of the National Institute for Health and Care Excellence treatment threshold to ≥10% 10-year risk. Of patients falling below this treatment threshold, almost all were at increased lifetime risk as measured by JBS3, and of these, the majority had elevated hsCRP levels. These patients with high absolute risk may benefit from early primary CVD prevention.
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Affiliation(s)
- Ieuan Johns
- Western Health, Victoria, Saint Albans, Australia
| | | | - Jesús Medina
- Medical Evidence and Observational Research, AstraZeneca, Madrid, Spain
| | - Nicholas Ossei-Gerning
- Cardiology Department, University Hospital of Wales, Cardiff and Vale University Health Board, Cardiff, UK
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Rhainds D, Brodeur MR, Tardif JC. Lipids, Apolipoproteins, and Inflammatory Biomarkers of Cardiovascular Risk: What Have We Learned? Clin Pharmacol Ther 2018; 104:244-256. [DOI: 10.1002/cpt.1114] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 04/19/2018] [Accepted: 05/09/2018] [Indexed: 11/11/2022]
Affiliation(s)
| | | | - Jean-Claude Tardif
- Montreal Heart Institute; Montreal Quebec Canada
- Faculty of Medicine; Université de Montréal; Montreal Quebec Canada
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Soko ND, Masimirembwa C, Dandara C. Pharmacogenomics of Rosuvastatin: A Glocal (Global+Local) African Perspective and Expert Review on a Statin Drug. OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY 2018; 20:498-509. [PMID: 27631189 DOI: 10.1089/omi.2016.0114] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The incidence of cardiovascular diseases (CVDs) in African populations residing in the African continent is on the rise fueled by both a steady increase in CVD risk factors and comorbidities such as human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), tuberculosis, and parasitic diseases such as bilharzia. Statins are recommended together with lifestyle changes in the treatment of hypercholesterolemia and overall reduction of cardiovascular events. Rosuvastatin in particular is an attractive candidate in the management of CVDs in African populations often plagued with multimorbidities owing to both its potency and low drug-to-drug interaction potential. In this expert review, we describe the pharmacogenetics of rosuvastatin and how it may instrumentally affect the African populations. We describe polymorphisms in the candidate genes, ABCG2, SLCO1B1, CYP2C9, APOE, PCSK9, LDLR, LPA, and HMGCR, and their role in the potency and safety of rosuvastatin therapy. We report on qualitative and quantitative differences in the distribution of genetic variants that affect efficacy and toxicity of rosuvastatin. These differences are observed across world populations (Caucasian, European, and Asian) as well as within African populations. Finally, we advocate for extensive pharmacogenetic studies in African populations that take into account the genetic diversity of intra-African ethnic groups and the genetic differences between African populations and other global populations, with a collaborative and collective aim to provide effective and safe use of rosuvastatin in management of CVD in Africa. Our key thesis presented in this innovation field analysis is that rosuvastatin precision medicine can serve as a veritable Glocal (Global and Local) model to offer pharmacogenetic-guided optimal therapeutics for the public in both developing and developed regions of the world.
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Affiliation(s)
- Nyarai D Soko
- 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, and University of Cape Town , Cape Town, South Africa
| | - Collen Masimirembwa
- 2 African Institute of Biomedical Science and Technology (AiBST) , Wilkins Hospital, Harare, Zimbabwe .,3 Clinical Pharmacology, Department of Medicine, University of Cape Town , Cape Town, South Africa
| | - Collet Dandara
- 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, and University of Cape Town , Cape Town, South Africa
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12
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Kostapanos MS, Elisaf MS. Statins and mortality: the untold story. Br J Clin Pharmacol 2017; 83:938-941. [PMID: 27921324 PMCID: PMC5401967 DOI: 10.1111/bcp.13202] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 10/21/2016] [Accepted: 11/16/2016] [Indexed: 12/12/2022] Open
Abstract
Statins are first-line evidence-based drugs for the management of dyslipidaemias and to reduce the risk of cardiovascular events. However, statin clinical trials have shown marginally significant benefits on mortality, especially in the primary prevention setting. A major limitation of those trials is their relatively short follow-up. A reduced number of fatal events within a 5-year follow-up make mortality benefits unlikely to arise. This is particularly relevant for the primary prevention trials, where the risk of cardiovascular death is low. The short follow-up is a limitation for safety assessments too. However, extended major statin trials failed to detect any major safety concerns. Safety and efficacy assessments are even more complicated considering the differences of cardiovascular risk status in primary prevention individuals, and also given some potential ethnic and inter-individual genetic variations in response to statin treatment. Considerable evidence suggests a favourable risk-benefit balance for statin treatment. It can be assumed that statins reduce mortality in the long term by preventing cardiovascular events with complications that reduce lifespan. Unfortunately, this hypothesis cannot be proven as there is no current ethical basis on designing long-term placebo-controlled statin trials. Nevertheless, by effectively reducing disabilities related to cardiovascular events, statins have major benefits for public health. Therefore, clinicians should not withhold statin treatment awaiting proof of mortality benefits, as this may remain an 'untold story'.
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Affiliation(s)
- Michael S. Kostapanos
- Clinical Pharmacology Unit, Addenbrooke's HospitalCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - Moses S. Elisaf
- Department of Internal Medicine, Medical SchoolUniversity of IoanninaIoanninaGreece
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Wyss R, Glynn RJ, Gagne JJ. A Review of Disease Risk Scores and Their Application in Pharmacoepidemiology. CURR EPIDEMIOL REP 2016. [DOI: 10.1007/s40471-016-0088-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Ancheta IB, Battie CA, Volgman AS, Ancheta CV, Palaniappan L. Cardiovascular Disease Risk Score: Results from the Filipino-American Women Cardiovascular Study. J Racial Ethn Health Disparities 2016; 4:25-34. [PMID: 27294770 DOI: 10.1007/s40615-015-0196-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2015] [Revised: 11/11/2015] [Accepted: 11/27/2015] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Although cardiovascular disease (CVD) is a leading cause of morbidity and mortality of Filipino-Americans, conventional CVD risk calculators may not be accurate for this population. CVD risk scores of a group of Filipino-American women (FAW) were measured using the major risk calculators. Secondly, the sensitivity of the various calculators to obesity was determined. METHODS This is a cross-sectional descriptive study that enrolled 40-65-year-old FAW (n = 236), during a community-based health screening study. Ten-year CVD risk was calculated using the Framingham Risk Score (FRS), Reynolds Risk Score (RRS), and Atherosclerotic Cardiovascular Disease (ASCVD) calculators. The 30-year risk FRS and the lifetime ASCVD calculators were also determined. RESULTS Levels of predicted CVD risk varied as a function of the calculator. The 10-year ASCVD calculator classified 12 % of participants with ≥10 % risk, but the 10-year FRS and RRS calculators classified all participants with ≤10 % risk. The 30-year "Hard" Lipid and BMI FRS calculators classified 32 and 43 % of participants with high (≥20 %) risk, respectively, while 95 % of participants were classified with ≥20 % risk by the lifetime ASCVD calculator. The percent of participants with elevated CVD risk increased as a function of waist circumference for most risk score calculators. CONCLUSIONS Differences in risk score as a function of the risk score calculator indicate the need for outcome studies in this population. Increased waist circumference was associated with increased CVD risk scores underscoring the need for obesity control as a primary prevention of CVD in FAW.
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Lindhardsen J, Kristensen SL, Ahlehoff O. Management of Cardiovascular Risk in Patients with Chronic Inflammatory Diseases: Current Evidence and Future Perspectives. Am J Cardiovasc Drugs 2016; 16:1-8. [PMID: 26293235 DOI: 10.1007/s40256-015-0141-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
An increased risk of cardiovascular disease (CVD) has been observed in a range of chronic inflammatory diseases (CID), including rheumatoid arthritis (RA), psoriasis, inflammatory bowel diseases (IBD), and systemic lupus erythematosus (SLE). The increased risk of CVDs and reduced life expectancy in these conditions has stimulated considerable research and started an ongoing discussion on the need for a multidisciplinary approach and dedicated guidelines on CVD prevention in these patients. In addition, the possibility of inhibiting inflammation as a means to preventing CVD in these patients has gained considerable interest in recent years. We briefly summarize the current level of evidence of the association between CIDs and CVD and cardiovascular risk management recommendations. Perspectives of ongoing and planned trials are discussed in consideration of potential ways to improve primary and secondary CVD prevention in patients with CID.
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Affiliation(s)
- Jesper Lindhardsen
- Department of Internal Medicine, Copenhagen University Hospital Slagelse, 4200, Slagelse, Denmark
| | - Søren Lund Kristensen
- Department of Cardiology, Copenhagen University Hospital Gentofte, 2900, Hellerup, Denmark
| | - Ole Ahlehoff
- Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 7, 2100, Copenhagen, Denmark.
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Viljoen JE, Christie CJA. The change in motivating factors influencing commencement, adherence and retention to a supervised resistance training programme in previously sedentary post-menopausal women: a prospective cohort study. BMC Public Health 2015; 15:236. [PMID: 25884764 PMCID: PMC4362642 DOI: 10.1186/s12889-015-1543-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 02/16/2015] [Indexed: 02/04/2023] Open
Abstract
Background Understanding motivators for exercise participation in post-menopausal women may impact retention to exercise programmes and inform intervention trial designs. The purpose of this investigation was to assess self-reported motivational factors influencing adherence and retention to a 24-week progressive resistance training programme. Methods Post-menopausal females (n = 34) were passively recruited to undertake a 24-week progressive resistance training protocol, in small-group sessions, on three non-consecutive days of the week. Attendance was recorded by the researcher. Qualitative reports were sourced from the sample for four phases of the study: pre-study (prior to week 1), recruitment (week 1), during study (weeks 2 – 24), and post-intervention (beyond week 24). Responses were categorised according to ten descriptors: specific health index improvement, education, flexibility of time, social contact, conscience (loyalty to the researcher), wellness, weight management, organisation parameters (pertaining to the study programme) and enjoyment of the exercises. Results Of the initial sample, 76.5% (n = 26) met the specified ≥80% attendance criterion. The primary findings were that motivation to volunteer for the study was driven by a perceived need for a structured exercise programme (50% of respondents). A commitment to the researcher was the primary motivator for continued adherence to the study for 50% of participants. Social contact with other participants was cited by 60% of the sample as the primary reason for adherence for the full duration of 24 weeks. A desire to maintain the “wellness” derived from the programme was cited by 60% as a reason for continuing an exercise routine post-study. Conclusion This study identified that routine and supervision initially attract women to exercise programmes, while social cohesion of the group setting contributes to retention over time. Understanding the changing nature of motivating factors may contribute to better overall adherence and retention to exercise programmes and interventions.
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Affiliation(s)
- Janet Erica Viljoen
- Department of Human Kinetics and Ergonomics, Rhodes University, African Street, PO Box 94, Grahamstown, 6140, South Africa.
| | - Candice Jo-Anne Christie
- Department of Human Kinetics and Ergonomics, Rhodes University, African Street, PO Box 94, Grahamstown, 6140, South Africa.
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Li L, Zhang P, Tian JH, Yang K, Cochrane Vascular Group. Statins for primary prevention of venous thromboembolism. Cochrane Database Syst Rev 2014; 2014:CD008203. [PMID: 25518837 PMCID: PMC11127252 DOI: 10.1002/14651858.cd008203.pub3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Venous thromboembolism (VTE) is common in clinical practice. The efficacy of statins in the primary prevention of VTE remains unproven. This is an update of the review first published in 2011. OBJECTIVES To assess the efficacy of statins in the primary prevention of VTE. SEARCH METHODS For this update the Cochrane Peripheral Vascular Diseases (PVD) Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and CENTRAL (2014, Issue 1). SELECTION CRITERIA Randomised controlled trials (RCTs) that assessed statins in the primary prevention of VTE were considered. The outcomes we evaluated were the rates of VTE, cardiovascular and cerebrovascular events, death and adverse events. Two authors (L Li, JH Tian) independently selected RCTs against the inclusion criteria. Disagreements were resolved by discussion with a third author (KH Yang). DATA COLLECTION AND ANALYSIS Data extraction was independently carried out by two authors (L Li, JH Tian). Disagreements were resolved by discussion with a third author (PZ Zhang). Two authors (L Li, JH Tian) independently assessed the risk of bias according to a standard quality checklist provided by the PVD Group. MAIN RESULTS For this update we included one RCT with 17,802 participants that assessed rosuvastatin compared with placebo for the prevention of VTE. The quality of the evidence was moderate because of imprecision, as the required sample size for the outcomes of this review was not achieved. Analysis showed that when compared with placebo rosuvastatin reduced the incidence of VTE (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.37 to 0.86) and deep vein thrombosis (DVT) (OR 0.45, 95% CI 0.25 to 0.79), the risk of any (fatal and non-fatal) myocardial infarction (MI) (OR 0.45, 95% CI 0.30 to 0.69), and any (fatal and non-fatal) stroke (OR 0.51, 95% CI 0.34 to 0.78). There was no difference in the incidence of pulmonary embolism (PE) (OR 0.77, 95% CI 0.41 to 1.46), fatal MI (OR 1.50, 95% CI 0.53 to 4.22), fatal stroke (OR 0.30, 95% CI 0.08 to 1.09) or death after VTE (OR 0.50, 95% CI 0.20 to 1.24). The incidence of any serious adverse events was no different between the rosuvastatin and placebo groups (OR 1.07, 95% CI 0.95 to 1.20). AUTHORS' CONCLUSIONS Available evidence showed that rosuvastatin was associated with a reduced incidence of VTE, but the evidence was limited to a single RCT and any firm conclusions and suggestions could be not drawn. Randomised controlled trials of statins (including rosuvastatin) are needed to evaluate their efficacy in the prevention of VTE.
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Affiliation(s)
- Lun Li
- Lanzhou UniversityThe First Clinical College of Lanzhou University; Evidence‐Based Medicine Center, School of Basic Medical SciencesNo. 199, Donggang West RoadLanzhou CityGansuChina730000
| | - Peizhen Zhang
- Hospital of Lanzhou CityMaternity and Child‐careWest ShiziLanzhou CityGanshuChina730000
| | - Jin Hui Tian
- Lanzhou UniversityEvidence‐Based Medicine Center, School of Basic Medical SciencesNo. 199, Donggang West RoadLanzhou CityGansuChina730000
| | - KeHu Yang
- Lanzhou UniversityKey Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu ProvinceNo. 199, Donggang West RoadLanzhou CityGansuChina730000
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Kostapanos MS, Rizos CV, Elisaf MS. Benefit-risk assessment of rosuvastatin in the treatment of atherosclerosis and related diseases. Drug Saf 2014; 37:481-500. [PMID: 24788803 DOI: 10.1007/s40264-014-0169-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Rosuvastatin has been marketed for approximately a decade. In this review we critically discuss available evidence on the benefits and risks from its use. In clinical trials using rosuvastatin, 'lowest is best' was relevant for on-treatment low-density lipoprotein cholesterol levels. Targeting levels <50 mg/dl was associated with the greatest decrease in vascular morbidity/mortality in the primary prevention setting. Also, such reduction can induce atherosclerosis regression without increasing the risk of adverse effects. Pooled data suggest that the safety profile of rosuvastatin is not different from that of other statins. It was estimated that rosuvastatin-associated absolute hazards of muscle-, liver- and renal-related adverse effects are lower than the corresponding vascular benefits in moderate vascular risk individuals. However, these data are subject to biases and need confirmation on a prospective basis. Significant liver enzyme elevations are rare. These often imply underlying non-alcoholic fatty liver disease (NAFLD), which is associated with increased vascular risk. Rosuvastatin can improve biochemical biomarkers and histological score of NAFLD. Whether this benefit is associated with vascular risk reduction should be assessed by prospective studies. Both chronic kidney disease and albuminuria independently predict vascular morbidity and mortality. Rosuvastatin improved the estimated glomerular filtration rate and decreased albuminuria in patients with moderately impaired kidney function. Also, vascular morbidity and mortality might be reduced in these patients. The same was not relevant in end-stage renal disease. Rosuvastatin-induced proteinuria appears to be of tubular origin, not relating to kidney injury. Rosuvastatin increases the risk of new-onset diabetes by dose-dependently impairing insulin sensitivity. Obese individuals with prediabetes appear to be predominantly affected. However, absolute vascular benefits of rosuvastatin may counterbalance this risk. Rosuvastatin is effective for the prevention and management of atherosclerotic vascular disease. Individualization of its use can maximize benefits and reduce the risk of adverse effects.
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Affiliation(s)
- Michael S Kostapanos
- Department of Internal Medicine, Medical School, University of Ioannina, St. Niarchou Avenue, 45110, Ioannina, Greece
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Barrios V, Escobar C, Zamorano JL. Searching the place of pitavastatin in the current treatment of patients with dyslipidemia. Expert Rev Cardiovasc Ther 2014; 11:1597-612. [DOI: 10.1586/14779072.2013.844546] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Hamirani YS, Katz R, Nasir K, Zeb I, Blaha MJ, Blumenthal RS, Kronmal RN, Budoff MJ. Association between inflammatory markers and liver fat: The Multi-Ethnic Study of Atherosclerosis. ACTA ACUST UNITED AC 2014; 5. [PMID: 25598995 DOI: 10.4172/2155-9880.1000344] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a common liver disease. Data is emerging that an independent association between markers of subclinical atherosclerosis and NAFLD exists and it may be considered as an independent predictor of cardiovascular (CV) outcomes. We aim to better characterize the relationship between NAFLD and inflammatory markers in a multi-ethnic cohort by assessing fatty liver on computed tomography (CT) scans. METHODS The Multi-Ethnic Study of Atherosclerosis (MESA) is a longitudinal, population-based study from four ethnic groups free of CV disease at baseline. The inflammatory markers studied include: C-reactive protein (CRP) and interleukin 6 (IL-6). On CT scans liver-to-spleen ratio (LSR: Hounsfield Units (HU) of the liver divided by HU of spleen) of <1 and liver attenuation of <40 HU were used as criteria for fatty liver. Unadjusted and adjusted multivariate linear and logistic regression analysis was performed. RESULTS 4038 participants amongst 6814 MESA population with visible spleen on the CT scan, available CRP and IL-6 levels and no reported liver cirrhosis were included. The average age was 61 +/- 10 years, 37% Caucasians and 45% were males. Mean CRP and IL-6 were 2.36 mg/dl and 1.37 pg/ml respectively. 696 participants (17%) had LSR of <1 and 253 (6%) had liver attenuation of <40 HU. When using LSR <1 as a continuous variable, the correlation (adjusted odds ratio (OR)) with CRP >2.0 was 0.037 (95% CI: 0.02-0.054) and with IL-6 was 0.014 (95% CI: 0.004-0.023). On the other hand when presence and absence of LSR <1 was considered, higher ORs for association with CRP >2: 1.41 (95% CI: 1.16 to 1.73) and IL6:1.18 (95% CI: 1.05 to 1.31) were found. Similarly, the adjusted association of per unit decrease in liver attenuation with CRP>2 was 1.92 (95% CI: 1.20 to 2.63) while for IL-6 was 1.08 (95% CI: 0.69 to 1.47). When considering presence and absence of liver attenuation <40 HU the OR for CRP >2 was 2.27 (95% CI: 1.62 to 3.16) and for IL-6 was 1.33 (95% CI: 1.13 to 1.58). CONCLUSION CRP and IL-6 levels were found to be significantly associated with liver fat assessed on CT scan after adjusting for other risk factors for atherosclerosis.
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Affiliation(s)
- Yasmin S Hamirani
- Cardiovascular Imaging Fellow, Los Angeles Biomedical Research Institute at Harbor-UCLA Ronit Katz, DPhil
| | | | - Khurram Nasir
- Adjunct Assistant Professor of Medicine, Ciccarone Center for Preventive Cardiology, Johns Hopkins University, Baltimore, MD
| | | | - Michael J Blaha
- Assistant Professor of Medicine, Ciccarone Center for Preventive Cardiology, Johns Hopkins University, Baltimore, MD
| | - Roger S Blumenthal
- Professor of Medicine, Ciccarone Centre of Preventive Cardiology, Johns Hopkins University, Baltimore, MD
| | | | - Matthew J Budoff
- Professor of Medicine, Los Angeles Biomedical Research Institute at Harbor-ULCA, Torrance, CA
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Bittencourt MS, Blaha MJ, Blankstein R, Budoff M, Vargas JD, Blumenthal RS, Agatston AS, Nasir K. Polypill therapy, subclinical atherosclerosis, and cardiovascular events-implications for the use of preventive pharmacotherapy: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 2013; 63:434-43. [PMID: 24161320 DOI: 10.1016/j.jacc.2013.08.1640] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Revised: 07/18/2013] [Accepted: 08/14/2013] [Indexed: 10/26/2022]
Abstract
OBJECTIVES This study examines whether the coronary artery calcium (CAC) score can be used to define the target population to treat with a polypill. BACKGROUND Prior studies have suggested a single polypill to reduce cardiovascular disease (CVD) at the population level. METHODS Participants from MESA (Multi-Ethnic Study of Atherosclerosis) were stratified using the criteria of 4 polypill studies (TIPS [The Indian Polycap Study], Poly-Iran, Wald, and the PILL [Program to Improve Life and Longevity] Collaboration). We compared coronary heart disease (CHD) and CVD event rates and calculated the 5-year number needed to treat (NNT) after stratification based on the CAC score. RESULTS Among MESA participants eligible for TIPS, Poly-Iran, Wald, and the PILL Collaboration, CAC = 0 was observed in 58.6%, 54.5%, 38.9%, and 40.8%, respectively. The rate of CHD events among those with CAC = 0 varied from 1.2 to 1.9 events per 1,000 person-years, those with CAC scores from 1 to 100 had event rates ranging from 4.1 to 5.5, and in those with CAC scores >100 the event rate ranged from 11.6 to 13.3. The estimated 5-year NNT to prevent 1 CVD event ranged from 81-130 for patients with CAC = 0, 38-54 for those with CAC scores from 1 to 100, and 18-20 for those with CAC scores >100. CONCLUSIONS In MESA, among individuals eligible for treatment with the polypill, the majority of CHD and CVD events occurred in those with CAC scores >100. The group with CAC = 0 had a very low event rate and a high projected NNT. The avoidance of treatment in individuals with CAC = 0 could allow for significant reductions in the population considered for treatment, with a more selective use of the polypill and, as a result, avoidance of treatment in those who are unlikely to benefit.
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Affiliation(s)
- Márcio Sommer Bittencourt
- Non-Invasive Cardiovascular Imaging Program, Departments of Medicine (Cardiovascular Division) and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Michael J Blaha
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland
| | - Ron Blankstein
- Non-Invasive Cardiovascular Imaging Program, Departments of Medicine (Cardiovascular Division) and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Matthew Budoff
- Division of Cardiology, Los Angeles Biomedical Research Institute at Harbour-UCLA, Torrance, California
| | - Jose D Vargas
- Cardiology Division, Johns Hopkins Hospital, Baltimore, Maryland; Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland
| | - Roger S Blumenthal
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland
| | - Arthur S Agatston
- Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, Florida; Department of Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Khurram Nasir
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland; Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, Florida; Department of Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami, Florida; Baptist Cardiovascular Institute, Baptist Health South Florida, Miami, Florida.
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Minder CM, Blumenthal RS, Blaha MJ. Statins for primary prevention of cardiovascular disease: the benefits outweigh the risks. Curr Opin Cardiol 2013; 28:554-60. [PMID: 23928920 DOI: 10.1097/hco.0b013e32836429e6] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Statins significantly reduce cardiovascular morbidity and mortality in patients with and without coronary heart disease. Recently, much debate has focused on use of statins for primary prevention following a class-wide safety label change by the US Food and Drug Administration amidst concerns of worsened hyperglycemia. Here, we review the evidence for statins in primary prevention and offer guidance for their appropriate use. RECENT FINDINGS Two meta-analyses published since 2012 unequivocally support statins for primary prevention. Data from the Cholesterol Treatment Trialists' Collaborators demonstrated a 9% [relative risk (RR) 0.91, 95% confidence interval (CI) 0.85-0.97] reduction in all-cause mortality and a 25% (RR 0.75, 95% CI 0.70-0.80) reduction in major vascular events per 1.0 mmol/l reduction in low-density lipoprotein cholesterol, even among low-risk patients. A 2013 Cochrane review corroborated these findings including a 14% (OR 0.86, 95% CI 0.79-0.94) reduction in all-cause mortality and a 25% (RR 0.75, 95% CI 0.70-0.81) reduction in cardiovascular disease events with statin therapy despite an 18% (RR 1.18, 95% CI 1.01-1.39) increase in incident diabetes. SUMMARY Statins effectively lower atherogenic lipoproteins and result in clinically significant reductions in cardiovascular morbidity and mortality. When well tolerated, the cardiovascular benefits of statins for primary prevention generally far outweigh the reported harms.
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Affiliation(s)
- C Michael Minder
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Maryland 21287, USA
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The evolution or revolution of statin therapy in primary prevention: where do we go from here? Curr Atheroscler Rep 2013; 15:298. [PMID: 23299639 DOI: 10.1007/s11883-012-0298-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
CHD morbidity and mortality rates have more than halved since their peak in the 1960s and 1970s. This trend is a result of many factors; however, primary prevention provides the bulk of this benefit. Despite this tremendous progress, cardiovascular disease remains the major cause of death and this trend is projected to persist given the continuous growth in those aged 65 years or greater. Although statin therapy has been a main contributor to a primary prevention strategy, there is still controversy about exposing a large healthy population to long-term statin therapy. Advocates contend the mortality benefits from an aggressive statin approach would remove heart disease from its perch as the greatest killer of Americans and stroke mortality would drop from third to fifth place. Those advocating a much more conservative approach contend the data are not available to expose a healthy population to lifelong statin therapy given limited data on mortality, potential adverse events, and considerable costs. Given these opposing views, this summary of the evolution of statin therapy for the primary prevention of cardiovascular disease will review the major factors fueling this debate.
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Abramovits W, Oquendo M. Introduction to Autoinflammatory Syndromes and Diseases. Dermatol Clin 2013; 31:363-85. [DOI: 10.1016/j.det.2013.04.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Gas chromatography analysis of serum cholesterol synthesis and absorption markers used to predict the efficacy of simvastatin in patients with coronary heart disease. Clin Biochem 2013; 46:993-998. [PMID: 23598259 DOI: 10.1016/j.clinbiochem.2013.04.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2013] [Revised: 03/27/2013] [Accepted: 04/05/2013] [Indexed: 12/21/2022]
Abstract
OBJECTIVES We investigated the changes in cholesterol absorption and synthesis markers before and after simvastatin therapy in Chinese patients with coronary heart disease. DESIGN AND METHOD We developed a gas chromatography method to identify cholesterol synthesis and absorption markers and measured them in patients with coronary heart disease. We then tested their use in predicting the efficacy of simvastatin in lowering cholesterol. Serum samples from 45 patients and 38 healthy humans (controls) were analyzed in a gas chromatography-flame ionization detector. RESULTS Squalene and five non-cholesterol sterols--desmosterol and lathosterol (synthesis markers) and campesterol, stigmasterol, and sitosterol (absorption markers)--were detected. The recovery rates of the markers were 95-102%. After simvastatin treatment for four weeks, the total cholesterol and low-density lipoprotein cholesterol levels had significantly decreased from the baseline values (p<0.05). The baseline lathosterol level was significantly higher in good responders than in poor responders (p<0.05), and the stigmasterol level was significantly lower in good responders than in poor responders (p<0.05). CONCLUSIONS This method should be suitable for the detection of serum squalene and non-cholesterol markers and can be used to predict the efficacy of simvastatin in patients with coronary heart disease.
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Sondermeijer BM, Boekholdt SM, Rana JS, Kastelein JJ, Wareham NJ, Khaw KT. Clinical implications of JUPITER in a contemporary European population: the EPIC-Norfolk prospective population study. Eur Heart J 2013; 34:1350-7. [DOI: 10.1093/eurheartj/eht047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Taylor F, Huffman MD, Macedo AF, Moore THM, Burke M, Davey Smith G, Ward K, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013; 2013:CD004816. [PMID: 23440795 PMCID: PMC6481400 DOI: 10.1002/14651858.cd004816.pub5] [Citation(s) in RCA: 531] [Impact Index Per Article: 44.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of CVD is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with CVD. The case for primary prevention was uncertain when the last version of this review was published (2011) and in light of new data an update of this review is required. OBJECTIVES To assess the effects, both harms and benefits, of statins in people with no history of CVD. SEARCH METHODS To avoid duplication of effort, we checked reference lists of previous systematic reviews. The searches conducted in 2007 were updated in January 2012. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2022, Issue 4), MEDLINE OVID (1950 to December Week 4 2011) and EMBASE OVID (1980 to 2012 Week 1).There were no language restrictions. SELECTION CRITERIA We included randomised controlled trials of statins versus placebo or usual care control with minimum treatment duration of one year and follow-up of six months, in adults with no restrictions on total, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD. DATA COLLECTION AND ANALYSIS Two review authors independently selected studies for inclusion and extracted data. Outcomes included all-cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), revascularisation, change in total and LDL cholesterol concentrations, adverse events, quality of life and costs. Odds ratios (OR) and risk ratios (RR) were calculated for dichotomous data, and for continuous data, pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated. We contacted trial authors to obtain missing data. MAIN RESULTS The latest search found four new trials and updated follow-up data on three trials included in the original review. Eighteen randomised control trials (19 trial arms; 56,934 participants) were included. Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non-fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non-fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen. Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no evidence of any serious harm caused by statin prescription. Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life. Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta-analysis indicate that these benefits are similar in people at lower (< 1% per year) risk of a major cardiovascular event. AUTHORS' CONCLUSIONS Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins.
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Affiliation(s)
- Fiona Taylor
- Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
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Elewa U, Sanchez-Niño MD, Martin-Cleary C, Fernandez-Fernandez B, Egido J, Ortiz A. Cardiovascular risk biomarkers in CKD: the inflammation link and the road less traveled. Int Urol Nephrol 2012; 44:1731-44. [DOI: 10.1007/s11255-012-0271-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Accepted: 08/13/2012] [Indexed: 12/11/2022]
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Glynn RJ, Gagne JJ, Schneeweiss S. Role of disease risk scores in comparative effectiveness research with emerging therapies. Pharmacoepidemiol Drug Saf 2012; 21 Suppl 2:138-47. [PMID: 22552989 DOI: 10.1002/pds.3231] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Usefulness of propensity scores and regression models to balance potential confounders at treatment initiation may be limited for newly introduced therapies with evolving use patterns. OBJECTIVES To consider settings in which the disease risk score has theoretical advantages as a balancing score in comparative effectiveness research because of stability of disease risk and the availability of ample historical data on outcomes in people treated before introduction of the new therapy. METHODS We review the indications for and balancing properties of disease risk scores in the setting of evolving therapies and discuss alternative approaches for estimation. We illustrate development of a disease risk score in the context of the introduction of atorvastatin and the use of high-dose statin therapy beginning in 1997, based on data from 5668 older survivors of myocardial infarction who filled a statin prescription within 30 days after discharge from 1995 until 2004. Theoretical considerations suggested development of a disease risk score among nonusers of atorvastatin and high-dose statins during the period 1995-1997. RESULTS Observed risk of events increased from 11% to 35% across quintiles of the disease risk score, which had a C-statistic of 0.71. The score allowed control of many potential confounders even during early follow-up with few study endpoints. CONCLUSIONS Balancing on a disease risk score offers an attractive alternative to a propensity score in some settings such as newly marketed drugs and provides an important axis for evaluation of potential effect modification. Joint consideration of propensity and disease risk scores may be valuable.
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Affiliation(s)
- Robert J Glynn
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street, Boston, MA 02120, USA.
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Smith GN, Pudwell J, Walker M, Wen SW. Ten-Year, Thirty-Year, and Lifetime Cardiovascular Disease Risk Estimates Following a Pregnancy Complicated by Preeclampsia. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2012; 34:830-835. [DOI: 10.1016/s1701-2163(16)35381-6] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Mann DM, Shimbo D, Cushman M, Lakoski S, Greenland P, Blumenthal RS, Michos ED, Lloyd-Jones DM, Muntner P. C-reactive protein level and the incidence of eligibility for statin therapy: the multi-ethnic study of atherosclerosis. Clin Cardiol 2012; 36:15-20. [PMID: 22886783 DOI: 10.1002/clc.22046] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Revised: 07/10/2012] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Given the results of the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial, statin initiation may be considered for individuals with elevated high-sensitivity C-reactive protein (hsCRP). However, if followed prospectively, many individuals with elevated CRP may become statin eligible, limiting the impact of elevated CRP as a treatment indication. This analysis estimates the proportion of people with elevated CRP that become statin eligible over time. HYPOTHESIS Most people with elevated CRP become statin eligible over a short period of time. METHODS We followed 2153 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of cardiovascular disease and diabetes with low-density lipoprotein cholesterol <130 mg/dL at baseline to determine the proportion who become eligible for statins over 4.5 years. The proportion eligible for statin therapy, defined by the National Cholesterol Education Program (NCEP) 2004 updated guidelines, was calculated at baseline and during follow-up stratified by baseline CRP level (≥2 mg/L). RESULTS At baseline, 47% of the 2153 participants had elevated CRP. Among participants with elevated CRP, 29% met NCEP criteria for statins, compared with 28% without elevated CRP at baseline. By 1.5 years later, 26% and 22% (P = 0.09) of those with and without elevated CRP at baseline reached NCEP low-density lipoprotein cholesterol criteria and/or had started statins, respectively. These increased to 42% and 39% (P = 0.24) at 3 years and 59% and 52% (P = 0.01) at 4.5 years following baseline. CONCLUSIONS A substantial proportion of those with elevated CRP did not achieve NCEP-based statin eligibility over 4.5 years of follow-up. These findings suggest that many patients with elevated CRP may not receive the benefits of statins if CRP is not incorporated into the NCEP screening strategy.
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Affiliation(s)
- Devin M Mann
- Department of Medicine, Division of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts 02119, USA.
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Abstract
Strategies to reduce cardiovascular risk in primary and secondary prevention focus on optimization of low-density lipoprotein (LDL) cholesterol levels. Since the 2004 update of the Adult Treatment Panel (ATP) III guidelines, developments in the field of preventive cardiology have included new guidelines for women and for familial hypercholesterolemia; a risk assessment algorithm incorporating the inflammatory marker high-sensitivity C-reactive protein (hsCRP); and clinical trial data confirming the efficacy of aggressive lipid management. Within secondary prevention in particular, there is a need for more widespread use of intensive statin therapy to achieve low LDL cholesterol levels to reduce cardiovascular morbidity and mortality in patients at high risk for recurrent events. Within primary prevention, individuals with diabetes mellitus, mixed dyslipidemia, or elevated hsCRP also are at increased risk and may warrant treatment with aggressive lipid-modifying therapy. In this article, we provide an update on recent guidelines, risk algorithms, and trials related to the prevention and treatment of coronary artery disease.
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Samson RH, Nair DG. Influence and critique of the JUPITER Trial (Statins v no statins for primary prevention of cardiovascular events in patients with normal lipids and elevated C-reactive protein). Semin Vasc Surg 2012; 24:172-9. [PMID: 22153029 DOI: 10.1053/j.semvascsurg.2011.10.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Perhaps no recent trial in primary prevention of cardiovascular disease has resulted in more controversy than the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial, which was first published in 2008. The study evaluated a patient cohort previously considered to be "healthy," ie, men 50 years of age or older and women 60 years of age or older, who did not have a history of cardiovascular disease and, at the initial screening visit, had a low-density lipoprotein cholesterol level of <130 mg/dL (3.4 mmol/L) and a high-sensitivity C-reactive protein level ≥2.0 mg/L. The trial showed that rosuvastatin is a powerful statin that, at lower doses, can reduce low-density lipoprotein cholesterol to levels previously not seen with other agents. Concurrently, it can also reduce high-sensitivity C-reactive protein to levels below what are considered normal, but that might be more physiologic. In the trial participants who achieved such lowering, major cardiovascular events, including venous thromboembolic events, were reduced even in the short term. Despite these results, many still question whether the trial results should influence high-sensitivity C-reactive protein testing or the prescription of statins for individuals at low risk for cardiovascular disease.
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Minder CM, Blaha MJ, Horne A, Michos ED, Kaul S, Blumenthal RS. Evidence-based use of statins for primary prevention of cardiovascular disease. Am J Med 2012; 125:440-6. [PMID: 22387091 DOI: 10.1016/j.amjmed.2011.11.013] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2011] [Revised: 11/28/2011] [Accepted: 11/28/2011] [Indexed: 11/16/2022]
Abstract
Three-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, are widely available, inexpensive, and represent a potent therapy for treating elevated cholesterol. Current national guidelines put forth by the Adult Treatment Panel III recommend statins as part of a comprehensive primary prevention strategy for patients with elevated low-density lipoprotein cholesterol at increased risk for developing coronary heart disease within 10 years. Lack of a clear-cut mortality benefit in primary prevention has caused some to question the use of statins for patients without known coronary heart disease. On review of the literature, we conclude that current data support only a modest mortality benefit for statin primary prevention when assessed in the short term (<5 years). Of note, statin primary prevention results in a significant decrease in cardiovascular morbidity over the short and long term and a trend toward increased reduction in mortality over the long term. When appraised together, these data provide compelling evidence to support the use of statins for primary prevention in patients with risk factors for developing coronary heart disease over the next 10 years.
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Affiliation(s)
- C Michael Minder
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA
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Kommentar zu den neuen Leitlinien (2011) der Europäischen Gesellschaft für Kardiologie zum Management von Dyslipidämien. KARDIOLOGE 2012. [DOI: 10.1007/s12181-012-0420-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Cook NR, Paynter NP, Eaton CB, Manson JE, Martin LW, Robinson JG, Rossouw JE, Wassertheil-Smoller S, Ridker PM. Comparison of the Framingham and Reynolds Risk scores for global cardiovascular risk prediction in the multiethnic Women's Health Initiative. Circulation 2012; 125:1748-56, S1-11. [PMID: 22399535 PMCID: PMC3324658 DOI: 10.1161/circulationaha.111.075929] [Citation(s) in RCA: 184] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2011] [Accepted: 02/14/2012] [Indexed: 11/16/2022]
Abstract
BACKGROUND Framingham-based and Reynolds Risk scores for cardiovascular disease (CVD) prediction have not been directly compared in an independent validation cohort. METHODS AND RESULTS We selected a case-cohort sample of the multiethnic Women's Health Initiative Observational Cohort, comprising 1722 cases of major CVD (752 myocardial infarctions, 754 ischemic strokes, and 216 other CVD deaths) and a random subcohort of 1994 women without prior CVD. We estimated risk using the Adult Treatment Panel III (ATP-III) score, the Reynolds Risk Score, and the Framingham CVD model, reweighting to reflect cohort frequencies. Predicted 10-year risk varied widely between models, with ≥10% risk in 6%, 10%, and 41% of women with the ATP-III, Reynolds, and Framingham CVD models, respectively. Calibration was adequate for the Reynolds model, but the ATP-III and Framingham CVD models overestimated risk for coronary heart disease and major CVD, respectively. After recalibration, the Reynolds model demonstrated improved discrimination over the ATP-III model through a higher c statistic (0.765 versus 0.757; P=0.03), positive net reclassification improvement (NRI; 4.9%; P=0.02), and positive integrated discrimination improvement (4.1%; P<0.0001) overall, excluding diabetics (NRI=4.2%; P=0.01), and in white (NRI=4.3%; P=0.04) and black (NRI=11.4%; P=0.13) women. The Reynolds (NRI=12.9%; P<0.0001) and ATP-III (NRI=5.9%; P=0.0001) models demonstrated better discrimination than the Framingham CVD model. CONCLUSIONS The Reynolds Risk Score was better calibrated than the Framingham-based models in this large external validation cohort. The Reynolds score also showed improved discrimination overall and in black and white women. Large differences in risk estimates exist between models, with clinical implications for statin therapy.
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Affiliation(s)
- Nancy R Cook
- Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave E, Boston, MA 02215, USA.
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Luvai A, Mbagaya W, Hall AS, Barth JH. Rosuvastatin: a review of the pharmacology and clinical effectiveness in cardiovascular disease. CLINICAL MEDICINE INSIGHTS-CARDIOLOGY 2012; 6:17-33. [PMID: 22442638 PMCID: PMC3303484 DOI: 10.4137/cmc.s4324] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Rosuvastatin is a new generation HMG-CoA reductase inhibitor which exhibits some unique pharmacologic and pharmacokinetic properties. It has low extrahepatic tissue penetration, low potential for CYP3A4 interactions and substantial LDL-C lowering capacity and therefore has distinct advantages. We conducted a Medline literature search to identify rosuvastatin papers published in English. In this review, we outline the pharmacology of rosuvastatin, highlighting its efficacy and safety. We also review the major clinical trials with reference to primary and secondary prevention, familial hypercholesterolaemia and comparison with other statins. Finally we address its place in clinical practice.
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Affiliation(s)
- Ahai Luvai
- Department of Clinical Biochemistry, Leeds General Infirmary, LS1 3EX
| | - Wycliffe Mbagaya
- Department of Clinical Biochemistry, Leeds General Infirmary, LS1 3EX
| | | | - Julian H. Barth
- Department of Clinical Biochemistry, Leeds General Infirmary, LS1 3EX
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Ascunce RR, Berger JS, Weintraub HS, Schwartzbard A. The Role of Statin Therapy for Primary Prevention: What is the Evidence? Curr Atheroscler Rep 2012; 14:167-174. [PMID: 22286194 DOI: 10.1007/s11883-012-0229-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Almost one third of annual worldwide mortality is attributed to cardiovascular disease (CVD), making it the leading cause of global death. Dyslipidemia is a well-established risk factor for CVD and plays a pivotal role in the pathogenesis of atherosclerosis. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and lower low-density lipoprotein cholesterol, have emerged as the most effective therapy to date against atherothrombotic CVD. Although their role in secondary prevention of CVD is undisputed, it remains a topic for debate as to how widely they should be used for primary prevention. The Framingham Risk Score and the National Cholesterol Education Program Adult Treatment Panel III guidelines are the cornerstones for the current guidelines for primary prevention statin therapy. Although these guidelines serve as help to evaluate cardiovascular risk and effectively identify many patients who will benefit from statin therapy, there is a growing population of "intermediate-risk" patients who may be undertreated. Additional noninvasive tests may complement the traditional risk scores, potentially expanding the indications for statins.
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Abstract
BACKGROUND Venous thromboembolism (VTE) is common in clinical practice. The efficacy of statins in the primary prevention of VTE remains unproven. OBJECTIVES To assess the efficacy of statins in the primary prevention of VTE. SEARCH METHODS The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialised Register (last searched April 2011) and CENTRAL (2011, Issue 2). The authors searched MEDLINE (January 1966 to March 2011); EMBASE (1974 to March 2011); ISI Web of Knowledge (2001 to March 2011); the Chinese Biomedical Literature Database (1978 to March 2011) and other resources (including clinical trials registers, reference lists and presentations at various conferences. SELECTION CRITERIA Randomised controlled trials (RCTs) that assessed statins were considered. The outcomes we evaluated were the rates of VTE, cardiovascular and cerebrovascular events, death and adverse events. Two authors independently selected RCTs against inclusion criteria. Disagreements were resolved by discussion with a third author. DATA COLLECTION AND ANALYSIS Data extraction was independently carried out by two authors. Disagreements were resolved by discussion with a third author. Two authors independently assessed the risk of bias according to a standard quality checklist provided by the PVD Group. MAIN RESULTS We included one RCT (17 citations) with 17,802 participants that assessed rosuvastatin for preventing VTE. Our analysis showed that rosuvastatin reduced the incidence of VTE (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.37 to 0.86) and deep vein thrombosis (DVT) (OR 0.45, 95% CI 0.25 to 0.79), the risk of any (fatal and non-fatal) myocardial infarction (MI) (OR 0.45, 95% CI 0.30 to 0.69), any (fatal and non-fatal) stroke (OR 0.51, 95% CI 0.34 to 0.78), but did not reduce the incidence of pulmonary embolism (PE) (OR 0.77, 95% CI 0.41 to 1.46) and death after VTE (OR 0.50, 95% CI 0.20 to 1.24). Rosuvastatin did not reduce the incidence of any serious adverse event (OR 0.95, 95% CI 0.90 to 1.06). AUTHORS' CONCLUSIONS Available evidence showed that rosuvastatin was associated with a reduced incidence of VTE, but the evidence was limited to a single RCT. Randomised controlled trials of statins (including rosuvastatin) are needed to evaluate the efficacy of statins in the prevention of VTE.
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Affiliation(s)
- Lun Li
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, No. 199, Donggang West Road, Lanzhou City, Gansu, China, 730000
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Dorresteijn JAN, Visseren FLJ, Ridker PM, Wassink AMJ, Paynter NP, Steyerberg EW, van der Graaf Y, Cook NR. Estimating treatment effects for individual patients based on the results of randomised clinical trials. BMJ 2011; 343:d5888. [PMID: 21968126 PMCID: PMC3184644 DOI: 10.1136/bmj.d5888] [Citation(s) in RCA: 109] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES To predict treatment effects for individual patients based on data from randomised trials, taking rosuvastatin treatment in the primary prevention of cardiovascular disease as an example, and to evaluate the net benefit of making treatment decisions for individual patients based on a predicted absolute treatment effect. SETTING As an example, data were used from the Justification for the Use of Statins in Prevention (JUPITER) trial, a randomised controlled trial evaluating the effect of rosuvastatin 20 mg daily versus placebo on the occurrence of cardiovascular events (myocardial infarction, stroke, arterial revascularisation, admission to hospital for unstable angina, or death from cardiovascular causes). Population 17,802 healthy men and women who had low density lipoprotein cholesterol levels of less than 3.4 mmol/L and high sensitivity C reactive protein levels of 2.0 mg/L or more. METHODS Data from the Justification for the Use of Statins in Prevention trial were used to predict rosuvastatin treatment effect for individual patients based on existing risk scores (Framingham and Reynolds) and on a newly developed prediction model. We compared the net benefit of prediction based rosuvastatin treatment (selective treatment of patients whose predicted treatment effect exceeds a decision threshold) with the net benefit of treating either everyone or no one. RESULTS The median predicted 10 year absolute risk reduction for cardiovascular events was 4.4% (interquartile range 2.6-7.0%) based on the Framingham risk score, 4.2% (2.5-7.1%) based on the Reynolds score, and 3.9% (2.5-6.1%) based on the newly developed model (optimal fit model). Prediction based treatment was associated with more net benefit than treating everyone or no one, provided that the decision threshold was between 2% and 7%, and thus that the number willing to treat (NWT) to prevent one cardiovascular event over 10 years was between 15 and 50. CONCLUSIONS Data from randomised trials can be used to predict treatment effect in terms of absolute risk reduction for individual patients, based on a newly developed model or, if available, existing risk scores. The value of such prediction of treatment effect for medical decision making is conditional on the NWT to prevent one outcome event. Trial registration number Clinicaltrials.gov NCT00239681.
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Affiliation(s)
- Johannes A N Dorresteijn
- Department of Vascular Medicine, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, Netherlands
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Sever PS, Poulter NR, Chang CL, Hingorani A, Thom SA, Hughes AD, Welsh P, Sattar N. Evaluation of C-reactive protein prior to and on-treatment as a predictor of benefit from atorvastatin: observations from the Anglo-Scandinavian Cardiac Outcomes Trial. Eur Heart J 2011; 33:486-94. [PMID: 21798891 PMCID: PMC3279312 DOI: 10.1093/eurheartj/ehr262] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Aims We tested whether on-statin C-reactive protein is associated with cardiovascular (CV) outcome in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Methods and results ASCOT randomized a subset of 4853 patients with total cholesterol ≤6.5 mmol/L (250 mg/dL) to atorvastatin or placebo. In a case–control study during 5.5-year follow-up, 485 CV cases were age- and sex-matched with 1367 controls. Baseline LDL-cholesterol (LDL-c) and log-transformed C-reactive protein predicted CV events [odds ratio (OR) per 1 standard deviation (SD) 1.31 (95% confidence interval {CI}: 1.10, 1.56), P = 0.002 and OR 1.19 (1.05, 1.34), P = 0.006, respectively]. Including baseline C-reactive protein into a Framingham risk model very modestly improved risk prediction. Baseline C-reactive protein did not indicate the magnitude of the atorvastatin effect on CV outcome (P = 0.54). At 6 months, atorvastatin reduced median LDL-c by 40.3% and median C-reactive protein by 27.4%. In those randomized to atorvastatin, lower on-treatment LDL-c at 6 months was associated with a significant reduction in subsequent CV events [OR 0.41 (0.22, 0.75), P = 0.004] comparing those above and below the median (2.1 mmol/L). In contrast, C-reactive protein below the median (1.83 mg/L) compared with C-reactive protein above the median was not associated with a significant reduction in CV events [OR 0.86 (0.49, 1.51), P = 0.60]. Consequently, addition of on-treatment C-reactive protein to LDL-c did not improve prediction of statin efficacy. Conclusion Among these hypertensive patients selected on the basis of traditional CV risk factors, C-reactive protein did not usefully improve the prediction of CV events and, critically, reduction in C-reactive protein associated with statin therapy was not a predictor of CV outcome alone or in combination with LDL-c.
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Affiliation(s)
- Peter S Sever
- International Centre for Circulatory Health, Imperial College London, 59 North Wharf Road, London, UK.
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Kostapanos MS, Elisaf MS. JUPITER and satellites: Clinical implications of the JUPITER study and its secondary analyses. World J Cardiol 2011; 3:207-14. [PMID: 21860701 PMCID: PMC3158868 DOI: 10.4330/wjc.v3.i7.207] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2011] [Revised: 05/21/2011] [Accepted: 05/28/2011] [Indexed: 02/06/2023] Open
Abstract
THE JUSTIFICATION FOR THE USE OF STATINS IN PREVENTION: an intervention trial evaluating rosuvastatin (JUPITER) study was a real breakthrough in primary cardiovascular disease prevention with statins, since it was conducted in apparently healthy individuals with normal levels of low-density lipoprotein cholesterol (LDL-C < 130 mg/dL) and increased inflammatory state, reflected by a high concentration of high-sensitivity C-reactive protein (hs-CRP ≥ 2 mg/L). These individuals would not have qualified for statin treatment according to current treatment guidelines. In JUPITER, rosuvastatin was associated with significant reductions in cardiovascular outcomes as well as in overall mortality compared with placebo. In this paper the most important secondary analyses of the JUPITER trial are discussed, by focusing on their novel findings regarding the role of statins in primary prevention. Also, the characteristics of otherwise healthy normocholesterolemic subjects who are anticipated to benefit more from statin treatment in the clinical setting are discussed. Subjects at "intermediate" or "high" 10-year risk according to the Framingham score, those who exhibit low post-treatment levels of both LDL-C (< 70 mg/dL) and hs-CRP (< 1 mg/L), who are 70 years of age or older, as well as those with moderate chronic kidney disease (estimated glomerular filtration rate < 60 mL/min every 1.73 m(2)) are anticipated to benefit more from statin treatment. Unlikely other statin primary prevention trials, JUPITER added to our knowledge that statins may be effective drugs in the primary prevention of cardiovascular disease in normocholesterolemic individuals at moderate-to-high risk. Also, statin treatment may reduce the risk of venous thromboembolism and preserve renal function. An increase in physician-reported diabetes represents a major safety concern associated with the use of the most potent statins.
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Affiliation(s)
- Michael S Kostapanos
- Michael S Kostapanos, Moses S Elisaf, Department of Internal Medicine, School of Medicine, University of Ioannina, 45110, Ioannina, Greece
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Hlatky MA, Heidenreich PA. The year in epidemiology, health services research, and outcomes research. J Am Coll Cardiol 2011; 57:1859-66. [PMID: 21545941 DOI: 10.1016/j.jacc.2011.01.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2010] [Revised: 01/11/2011] [Accepted: 01/17/2011] [Indexed: 01/08/2023]
Affiliation(s)
- Mark A Hlatky
- Stanford University School of Medicine, Stanford, CA 94305, USA.
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Koenig W. Recent developments in cardiovascular risk assessment: relevance to the nephrologist. Nephrol Dial Transplant 2011; 26:3080-3. [PMID: 21633098 DOI: 10.1093/ndt/gfr283] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Lin GM, Li YH, Chu KM, Han CL. What else does the JUPITER trial add regarding C-reactive protein and cardiovascular disease? Int J Cardiol 2011; 149:387. [DOI: 10.1016/j.ijcard.2011.03.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2011] [Accepted: 03/03/2011] [Indexed: 11/21/2022]
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Lardizabal JA, Deedwania P. Lipid-lowering therapy with statins for the primary and secondary prevention of cardiovascular disease. Cardiol Clin 2011; 29:87-103. [PMID: 21257102 DOI: 10.1016/j.ccl.2010.10.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Cardiovascular disease (CVD) still ranks as the top cause of mortality worldwide. Lipid-modifying therapy has revolutionized the treatment of the disease and is partly responsible for the recent decline in deaths due to CVD. Treatment strategies have evolved since the introduction of the earlier lipid-lowering agents (fibrates, niacin, bile acid resins) to the advent of statins, which have become the standard drugs in cholesterol therapy. The strategy of using high-intensity statin therapy as the initial treatment approach in high-risk individuals, rather than focusing on specific cholesterol levels alone, remains a subject of debate.
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Affiliation(s)
- Joel A Lardizabal
- Division of Cardiology, Department of Medicine, University of California-San Francisco (Fresno Medical Education Program), Fresno, CA 93701, USA
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Kones R. Rosuvastatin, inflammation, C-reactive protein, JUPITER, and primary prevention of cardiovascular disease--a perspective. Drug Des Devel Ther 2010; 4:383-413. [PMID: 21267417 PMCID: PMC3023269 DOI: 10.2147/dddt.s10812] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The major public health concern worldwide is coronary heart disease, with dyslipidemia as a major risk factor. Statin drugs are recommended by several guidelines for both primary and secondary prevention. Rosuvastatin has been widely accepted because of its efficacy, potency, and superior safety profile. Inflammation is involved in all phases of atherosclerosis, with the process beginning in early youth and advancing relentlessly for decades throughout life. C-reactive protein (CRP) is a well-studied, nonspecific marker of inflammation which may reflect general health risk. Considerable evidence suggests CRP is an independent predictor of future cardiovascular events, but direct involvement in atherosclerosis remains controversial. Rosuvastatin is a synthetic, hydrophilic statin with unique stereochemistry. A large proportion of patients achieve evidence-based lipid targets while using the drug, and it slows progression and induces regression of atherosclerotic coronary lesions. Rosuvastatin lowers CRP levels significantly. The Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial was designed after the observation that when both low density lipoprotein and CRP were reduced, patients fared better than when only LDL was lowered. Advocates and critics alike acknowledge that the benefits of rosuvastatin in JUPITER were real. After a review, the US Food and Drug Administration extended the indications for rosuvastatin to include asymptomatic JUPITER-eligible individuals with one additional risk factor. The American Heart Association and Centers of Disease Control and Prevention had previously recognized the use of CRP in persons with "intermediate risk" as defined by global risk scores. The Canadian Cardiovascular Society guidelines went further and recommended use of statins in persons with low LDL and high CRP levels at intermediate risk. The JUPITER study focused attention on ostensibly healthy individuals with "normal" lipid profiles and high CRP values who benefited from statin therapy. The backdrop to JUPITER during this period was an increasing awareness of a rising cardiovascular risk burden and imperfect methods of risk evaluation, so that a significant number of individuals were being denied beneficial therapies. Other concerns have been a high level of residual risk in those who are treated, poor patient adherence, a need to follow guidelines more closely, a dual global epidemic of obesity and diabetes, and a progressively deteriorating level of physical activity in the population. Calls for new and more effective means of reducing risk for coronary heart disease are intensifying. In view of compelling evidence supporting earlier and aggressive therapy in people with high risk burdens, JUPITER simply offers another choice for stratification and earlier risk reduction in primary prevention patients. When indicated, and in individuals unwilling or unable to change their diet and lifestyles sufficiently, the benefits of statins greatly exceed the risks. Two side effects of interest are myotoxicity and an increase in the incidence of diabetes.
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Affiliation(s)
- Richard Kones
- The Cardiometabolic Research, Institute, Houston, TX 77054, USA.
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Ferdinand KC. Are cardiovascular benefits in statin lipid effects dependent on baseline lipid levels? Curr Atheroscler Rep 2010; 13:64-72. [PMID: 21104458 DOI: 10.1007/s11883-010-0149-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Statins reduce coronary heart disease (CHD) morbidity and mortality over a wide range of patients. The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) in subjects with elevated C-reactive protein, without vascular disease and below average low-density lipoprotein cholesterol (LDL-C) showed a 50% reduction in LDL-C with 20 mg/d of rosuvastatin and a reduction in cardiovascular events (hazard ratio 0.56 [95% CI, 0.46-0.69]; P < 0.00001), and a reduction in total mortality (20%; P < 0.02). Recent commentary has criticized perceived JUPITER design flaws and inappropriate influence. However, the Canadian 2009 guidelines cite JUPITER as class I evidence for statin benefit. Although the Cholesterol Treatment Trialists' (CTT) Collaborators showed that, regardless of pre-treatment levels, statins can significantly reduce CHD, major vascular events, and overall mortality, a recent primary prevention meta-analysis showed no decrease in all-cause mortality. Preconceived notions on statin benefit or harm do not enhance patient care and clinicians should individualize long-term statin therapy.
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Affiliation(s)
- Keith C Ferdinand
- Division of Cardiology, Emory University, 5355 Hunter Rd., Atlanta, GA 30349, USA.
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