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Le R, Nguyen MT, Allahwala MA, Psaltis JP, Marathe CS, Marathe JA, Psaltis PJ. Cardiovascular Protective Properties of GLP-1 Receptor Agonists: More than Just Diabetic and Weight Loss Drugs. J Clin Med 2024; 13:4674. [PMID: 39200816 PMCID: PMC11355214 DOI: 10.3390/jcm13164674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/06/2024] [Accepted: 08/07/2024] [Indexed: 09/02/2024] Open
Abstract
Owing to their potent glucose-lowering efficacy and substantial weight loss effects, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now considered part of the frontline therapeutic options to treat both type 2 diabetes mellitus and nondiabetic overweight/obesity. Stemming from successful demonstration of their cardiometabolic modulation and reduction of major adverse cardiovascular events in clinical outcome trials, GLP-1 RAs have since been validated as agents with compelling cardiovascular protective properties. Studies spanning from the bench to preclinical and large-scale randomised controlled trials have consistently corroborated the cardiovascular benefits of this pharmacological class. Most notably, there is converging evidence that they exert favourable effects on atherosclerotic ischaemic endpoints, with preclinical data indicating that they may do so by directly modifying the burden and composition of atherosclerotic plaques. This narrative review examines the underlying pharmacology and clinical evidence behind the cardiovascular benefits of GLP-1 RAs, with particular focus on atherosclerotic cardiovascular disease. It also delves into the mechanisms that underpin their putative plaque-modifying actions, addresses existing knowledge gaps and therapeutic challenges and looks to future developments in the field, including the use of combination incretin agents for diabetes and weight loss management.
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Affiliation(s)
- Richard Le
- College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia;
- Heart and Vascular Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide 5000, Australia; (M.T.N.); (M.A.A.); (J.A.M.)
| | - Mau T. Nguyen
- Heart and Vascular Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide 5000, Australia; (M.T.N.); (M.A.A.); (J.A.M.)
- Department of Cardiology, Central Adelaide Local Health Network, Adelaide 5000, Australia
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide 5005, Australia; (J.P.P.); (C.S.M.)
| | - Momina A. Allahwala
- Heart and Vascular Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide 5000, Australia; (M.T.N.); (M.A.A.); (J.A.M.)
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide 5005, Australia; (J.P.P.); (C.S.M.)
| | - James P. Psaltis
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide 5005, Australia; (J.P.P.); (C.S.M.)
| | - Chinmay S. Marathe
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide 5005, Australia; (J.P.P.); (C.S.M.)
- Department of Endocrinology, Central Adelaide Local Health Network, Adelaide 5000, Australia
| | - Jessica A. Marathe
- Heart and Vascular Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide 5000, Australia; (M.T.N.); (M.A.A.); (J.A.M.)
- Department of Cardiology, Central Adelaide Local Health Network, Adelaide 5000, Australia
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide 5005, Australia; (J.P.P.); (C.S.M.)
| | - Peter J. Psaltis
- Heart and Vascular Program, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide 5000, Australia; (M.T.N.); (M.A.A.); (J.A.M.)
- Department of Cardiology, Central Adelaide Local Health Network, Adelaide 5000, Australia
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide 5005, Australia; (J.P.P.); (C.S.M.)
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Ruiz-García A, Pallarés-Carratalá V, Serrano-Cumplido A, Escobar-Cervantes C, Barquilla-García A, Divisón-Garrote JA, Turégano-Yedro M, Prieto-Díaz MA, Cinza-Sanjurjo S, Alonso-Moreno FJ, Beato-Fernández P, García-Matarín L, Rey-Aldana D, Martín-Rioboó E, Moyá-Amengual A, Crespo-Sabarís R, Piera-Carbonell A, Romero-Vigara JC, Carrasco-Carrasco E, Velilla-Zancada S, Seoane-Vicente MC, Górriz-Teruel JL, Polo-García J, Barrios V. Evaluation of prophylaxis in primary prevention with acetylsalicylic acid in people with diabetes: A scoping review. Semergen 2022; 48:275-292. [PMID: 35181226 DOI: 10.1016/j.semerg.2021.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/07/2021] [Accepted: 12/03/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND The efficacy and safety of acetylsalicylic acid (ASA) prophylaxis for the primary prevention of atherosclerotic cardiovascular disease (ACVD) remain controversial in people with diabetes (DM) without ACVD, because the possible increased risk of major bleeding could outweigh the potential reduction in the risk of mortality and of major adverse cardiovascular events (MACE) considered individually or together. OBJECTIVE To evaluate the overall risk-benefit of ASA prophylaxis in primary prevention in people with DM and to compare the recommendations of the guidelines with the results of the meta-analyses (MA) and systematic reviews (SR). MATERIAL AND METHODS We searched Medline, Google Scholar, Embase, and the Cochrane Library for SR and MA published from 2009 to 2020 which compared the effects of ASA prophylaxis versus placebo or control followed up for at least one year in people with DM without ACVD. Heterogeneity among the randomized clinical trials (RCT) included in the SR and MA was assessed. Cardiovascular outcomes of efficacy (all-cause mortality [ACM], cardiovascular mortality [CVM], myocardial infarction [MI], stroke and MACE) and of safety (major bleeding events [MBE], major gastrointestinal bleeding events [MGIBE], and intracranial and extracranial bleeding) were shown. RESULTS The recommendations of 12 guidelines were evaluated. The results of 25 SR and MA that included a total of 20 RCT were assessed. None of the MA or SR showed that ASA prophylaxis decreased the risk of ACM, CVM or MI. Only two of the 19 SR and MA that evaluated ischemic stroke showed a decrease in the stroke risk (mean 20.0% [SD±5.7]), bordering on statistical significance. Almost half of the MA and SR showed, bordering on statistical significance, a risk reduction for the MACE composite endpoint (mean 10.5% [SD±3.3]). The significant increases in MGIBE risk ranged from 35% to 55%. The significant increases in the risk of MBE and extracraneal bleeding were 33.4% (SD±14.9) and 54.5% (SD±0.7) respectively. CONCLUSION The overall risk-benefit assessment of ASA prophylaxis in primary prevention suggests that it should not be applied in people with DM.
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Affiliation(s)
- A Ruiz-García
- Family Medicine, Pinto University Health Center, Pinto, Madrid, Spain; European University of Madrid, Villaviciosa de Odón, Madrid, Spain
| | - V Pallarés-Carratalá
- Family Medicine, Health Surveillance Unit, Mutual Insurance Union, Castellón, Spain; Medicine Department, Jaume I University, Castellón, Spain.
| | | | | | - A Barquilla-García
- Family Medicine, Trujillo Primary Care Team, Clinics of Herguijuela and Conquista de la Sierra), Cáceres, Spain
| | - J A Divisón-Garrote
- Family Medicine, Casas Ibáñez Health Center, Fuentealbilla Clinic, Albacete, Spain
| | | | - M A Prieto-Díaz
- Family Medicine, Vallobín - La Florida Health Center, Oviedo, Spain
| | - S Cinza-Sanjurjo
- Family Medicine, Porto do Son Health Center, Santiago de Compostela Health Area, Santiago de Compostela, Spain; Center for Biomedical Research Network on Cardiovascular Diseases (CIBERCV), Madrid, Spain
| | | | - P Beato-Fernández
- Family Medicine, Premia de Mar Primary Care Center, Catalan Institute of Health, Barcelona, Spain
| | - L García-Matarín
- Family Medicine, Aguadulce Sur Health Center, Roquetas de Mar, Almería, Spain
| | - D Rey-Aldana
- Family Medicine, Estrada Health Center, Pontevedra, Spain; USC-SEMERGEN Chair, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - E Martín-Rioboó
- Family Medicine, Maimónides Institute for Biomedical Research of Córdoba (IMIBIC), Reina Sofía Hospital, Poniente clinical management unit, Córdoba, Spain
| | - A Moyá-Amengual
- Occupational Medicine, Santa Catalina Health Center, Palma de Mallorca, Islas Baleares, Spain
| | - R Crespo-Sabarís
- Family Medicine, Primary Care Management of La Rioja Health Service, Logroño, La Rioja, Spain
| | | | | | | | | | | | - J L Górriz-Teruel
- Nephrology Service, University Clinical Hospital, Valencia, Spain; School of Medicine, University of Valencia, Valencia, Spain
| | - J Polo-García
- Family Medicine, Casar de Cáceres Health Center, Cáceres, Spain
| | - V Barrios
- Cardiology Service, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain
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Orozco-Beltrán D, Brotons Cuixart C, Alemán Sánchez JJ, Banegas Banegas JR, Cebrián-Cuenca AM, Gil Guillen VF, Martín Rioboó E, Navarro Pérez J. [Cardiovascular preventive recommendations. PAPPS 2020 update]. Aten Primaria 2020; 52 Suppl 2:5-31. [PMID: 33388118 PMCID: PMC7801219 DOI: 10.1016/j.aprim.2020.08.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 08/14/2020] [Indexed: 12/16/2022] Open
Abstract
The recommendations of the semFYC's Program for Preventive Activities and Health Promotion (PAPPS) for the prevention of cardiovascular diseases (CVD) are presented. The following sections are included: Epidemiological review, where the current morbidity and mortality of CVD in Spain and its evolution as well as the main risk factors are described; Cardiovascular (CV) risk tables and recommendations for the calculation of CV risk; Main risk factors such as arterial hypertension, dyslipidemia and diabetes mellitus, describing the method for their diagnosis, therapeutic objectives and recommendations for lifestyle measures and pharmacological treatment; Indications for antiplatelet therapy, and recommendations for screening of atrial fibrillation. The quality of testing and the strength of the recommendation are included in the main recommendations.
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Affiliation(s)
- Domingo Orozco-Beltrán
- Unidad de Investigación CS Cabo Huertas, Departamento San Juan de Alicante, Departamento de Medicina Clínica. Universidad Miguel Hernández, España.
| | | | | | | | | | | | - Enrique Martín Rioboó
- Instituto Maimónides de Investigación Biomédica de Córdoba IMIBIC Hospital Reina Sofía. Unidad de gestión clínica Poniente. Distrito sanitario Córdoba Guadalquivir, Córdoba, España
| | - Jorge Navarro Pérez
- Hospital Clínico Universitario, Departamento de Medicina, Universidad de Valencia, Instituto de Investigación INCLIVA, Valencia, España
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Caldeira D, Alves M, David C, Costa J, Ferreira JJ, Pinto FJ. Aspirin in the primary prevention of cardiovascular disease on diabetic patients: Systematic review and meta-analysis. Prim Care Diabetes 2020; 14:213-221. [PMID: 31791903 DOI: 10.1016/j.pcd.2019.11.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 11/02/2019] [Accepted: 11/06/2019] [Indexed: 12/12/2022]
Abstract
AIMS The publication of new trials brought additional data to the controversial topic of aspirin use in diabetic patients for primary prevention. Therefore, we aimed to systematically review all randomized controlled trials evaluating the clinical impact of aspirin in this setting. METHODS We searched for randomized controlled trials (RCTs) evaluating the impact of aspirin in patients with diabetes in primary prevention, in MEDLINE, EMBASE, CENTRAL (November/2018). The primary outcomes were all-cause mortality and the composite outcome of major adverse cardiovascular events (MACE). A meta-analysis was performed deriving risk ratios (RR) and 95% confidence intervals (CI). RESULTS All-cause mortality was not significantly reduced with RR 0.96 (95% CI 0.90-1.03; 7RCT; 27,595 patients). Regarding MACE, there was an 8% risk reduction (RR 0.92, 95% CI 0.84-0.999; I2=0%; 8RCT; 29,814 patients). The risks of major bleeding (RR 1.30, 95% CI 1.10-1.53; 2RCTs, 18,019 patients), and major GI bleeding (RR 1.39, 95% CI 1.08-1.80; 2RCTs, 18,019 patients) were significantly increased. The risks of cardiovascular mortality, myocardial infarction, stroke and amputation were not significantly different from control arm. CONCLUSIONS Aspirin use among diabetic patients in primary prevention appears was associated with increased risk of major bleeding, a modest decrease of MACE and lack of mortality benefit.
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Affiliation(s)
- Daniel Caldeira
- Centro Cardiovascular da Universidade de Lisboa - CCUL, CAML, Faculdade de Medicina, Universidade de Lisboa, Portugal; Serviço de Cardiologia, Hospital Universitário de Santa Maria - CHULN, Portugal; Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal.
| | - Mariana Alves
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal; Serviço de Medicina III, Hospital Pulido Valente, CHLN, Lisboa, Portugal
| | - Cláudio David
- Centro Cardiovascular da Universidade de Lisboa - CCUL, CAML, Faculdade de Medicina, Universidade de Lisboa, Portugal; Serviço de Cardiologia, Hospital Universitário de Santa Maria - CHULN, Portugal; Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Portugal
| | - João Costa
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal
| | - Joaquim J Ferreira
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal
| | - Fausto J Pinto
- Centro Cardiovascular da Universidade de Lisboa - CCUL, CAML, Faculdade de Medicina, Universidade de Lisboa, Portugal; Serviço de Cardiologia, Hospital Universitário de Santa Maria - CHULN, Portugal
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Puljak L, Riva N, Parmelli E, González-Lorenzo M, Moja L, Pieper D. Data extraction methods: an analysis of internal reporting discrepancies in single manuscripts and practical advice. J Clin Epidemiol 2019; 117:158-164. [PMID: 31541692 DOI: 10.1016/j.jclinepi.2019.09.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 06/12/2019] [Accepted: 09/09/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Data extraction from reports about experimental or observational studies is a crucial methodological step informing evidence syntheses, such as systematic reviews (SRs) and overviews of SRs. Reporting discrepancies were defined as pairs of statements that could not both be true. Authors of SRs and overviews of SRs can encounter reporting discrepancies among multiple sources when extracting data-a manuscript and a conference abstract, and a manuscript and a clinical trial registry. However, these discrepancies can also be found within a single manuscript published in a scientific journal. OBJECTIVES Hereby, we describe examples of internal reporting discrepancies that can be found in a single source, with the aim of raising awareness among authors of SRs and overviews of SRs about such potential methodological issues. CONCLUSIONS Authors of SRs and overviews of SRs should check whether the same information is reported in multiple places within a study and compare that information. Independent data extraction by two reviewers increases the chance of finding discrepancies, if they exist. We provide advice on how to deal with different types of discordances and how to report such discordances when conducting SRs and overviews of SRs.
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Affiliation(s)
- Livia Puljak
- Center for Evidence-Based Medicine and Health Care, Catholic University of Croatia, Zagreb, Croatia.
| | - Nicoletta Riva
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - Elena Parmelli
- Department of Epidemiology, Lazio Regional Health Service - ASL Roma 1, Rome, Italy
| | - Marien González-Lorenzo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Lorenzo Moja
- Policy, Access and Use (PAU), Essential Medicines and Health Products Department (EMP), World Health Organization, Geneva, Switzerland
| | - Dawid Pieper
- Witten/Herdecke University, School of Medicine, Cologne, Germany
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Seidu S, Kunutsor SK, Sesso HD, Gaziano JM, Buring JE, Roncaglioni MC, Khunti K. Aspirin has potential benefits for primary prevention of cardiovascular outcomes in diabetes: updated literature-based and individual participant data meta-analyses of randomized controlled trials. Cardiovasc Diabetol 2019; 18:70. [PMID: 31159806 PMCID: PMC6547459 DOI: 10.1186/s12933-019-0875-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Accepted: 05/25/2019] [Indexed: 12/22/2022] Open
Abstract
Background The clinical benefit of aspirin for the primary prevention of cardiovascular disease (CVD) in diabetes remains uncertain. To evaluate the efficacy and safety of aspirin for the primary prevention of cardiovascular outcomes and all-cause mortality events in people with diabetes, we conducted an updated meta-analysis of published randomised controlled trials (RCTs) and a pooled analysis of individual participant data (IPD) from three trials. Methods Randomised controlled trials of aspirin compared with placebo (or no treatment) in participants with diabetes with no known CVD were identified from MEDLINE, Embase, Cochrane Library, and manual search of bibliographies to January 2019. Relative risks with 95% confidence intervals were used as the summary measures of associations. Results We included 12 RCTs based on 34,227 participants with a median treatment duration of 5.0 years. Comparing aspirin use with no aspirin, there was a significant reduction in risk of major adverse cardiovascular events (MACE)0.89 (0.83–0.95), with a number needed to treat (NNT)of 95 (95% CI 61 to 208) to prevent one MACE over 5 years average follow-up. Evidence was lacking of heterogeneity and publication bias among contributing trials for MACE. Aspirin use had no effect on other endpoints including all-cause mortality; however, there was a significant reduction in stroke for aspirin dosage ≤ 100 mg/day 0.75 (0.59–0.95). There were no significant effects of aspirin use on major bleeding and other bleeding events, though some of the estimates were imprecise. Pooled IPD from the three trials (2306 participants) showed no significant evidence of an effect of aspirin on any of the outcomes evaluated; however, aspirin reduced the risk of MACE in non-smokers 0.70 (0.51–0.96) with a NNT of 33 (95% CI 20 to 246) to prevent one MACE. Conclusions Aspirin has potential benefits in cardiovascular primary prevention in diabetes. The use of low dose aspirin may need to be individualised and based on each individual’s baseline CVD and bleeding risk. Systematic review registration PROSPERO: CRD42019122326 Electronic supplementary material The online version of this article (10.1186/s12933-019-0875-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Samuel Seidu
- Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4WP, UK. .,Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4WP, UK.
| | - Setor K Kunutsor
- National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK.,Translational Health Sciences, Bristol Medical School, Musculoskeletal Research Unit, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital, Bristol, BS10 5NB, UK
| | - Howard D Sesso
- Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue, East-3rd Floor, Boston, MA, 02215, USA.,Department of Medicine, Division of Aging, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA
| | - J M Gaziano
- Department of Medicine, Division of Aging, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA
| | - J E Buring
- Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue, East-3rd Floor, Boston, MA, 02215, USA
| | | | - Kamlesh Khunti
- Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4WP, UK.,Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4WP, UK
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Lin MH, Lee CH, Lin C, Zou YF, Lu CH, Hsieh CH, Lee CH. Low-Dose Aspirin for the Primary Prevention of Cardiovascular Disease in Diabetic Individuals: A Meta-Analysis of Randomized Control Trials and Trial Sequential Analysis. J Clin Med 2019; 8:jcm8050609. [PMID: 31060297 PMCID: PMC6572181 DOI: 10.3390/jcm8050609] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 04/26/2019] [Accepted: 05/03/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Evidence of low-dose aspirin as the primary prevention strategy for cardiovascular disease (CVD) in diabetes are unclear. This study was designed to evaluate the effect of low-dose aspirin use for the primary prevention of CVD in diabetes. Methods: We collected randomized controlled trials of low-dose aspirin for the primary prevention of CVD in adults with diabetes lasting at least 12 months from Medline, Embase, and the Cochrane Library up to 10 November 2018. Two reviewers extracted data and appraised the reporting quality according to a predetermined protocol (CRD4201811830). This review was conducted using Cochrane standards, trial sequential analysis, and the Grading of Recommendation. The primary outcomes were major adverse cardiovascular events (MACE, including non-fatal myocardial infarction, ischemia stroke, and cardiovascular death) and an incidence of major hemorrhage (major intracranial hemorrhage and major gastrointestinal bleeding). Results: In this primary prevention (number = 29,814 participants) meta-analysis, low-dose aspirin use reduced the risk of MACE by 9% and increased the risk of major hemorrhage by 24%. The benefits were only observed in subjects of age ≥ 60 years while reducing the same risk of MACE. In efficacy, it reduced the risk of stroke but not myocardial infarction. No increase in all-cause mortality or cardiovascular death was observed. Conclusions: We suggested the use of low-dose aspirin as the primary prevention strategy for CVD in diabetes, particularly in an older population. The absolute benefits were largely counterbalanced by the bleeding hazard.
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Affiliation(s)
- Ming-Hsun Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
| | - Chien-Hsing Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
| | - Chin Lin
- School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan.
- Department of Research and Development, National Defense Medical Center, Taipei 11490, Taiwan.
| | - Yi-Fen Zou
- Department of Pharmacy, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
| | - Chieh-Hua Lu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
- Department of Medical Research, National Defense Medical Center, Taipei 11490, Taiwan.
| | - Chang-Hsun Hsieh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
| | - Cho-Hao Lee
- Division of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
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8
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Khan SU, Ul Abideen Asad Z, Khan MU, Talluri S, Ali F, Shahzeb Khan M, Lone AN, Mookadam F, Krasuski RA, Kaluski E. Aspirin for primary prevention of cardiovascular outcomes in diabetes mellitus: An updated systematic review and meta-analysis. Eur J Prev Cardiol 2019; 27:2034-2041. [PMID: 30700151 DOI: 10.1177/2047487319825510] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The safety and efficacy of aspirin for the primary prevention of cardiovascular disease in patients with diabetes mellitus remains controversial. DESIGN A meta-analysis to investigate the effects of aspirin for the prevention of cardiovascular disease in diabetes mellitus. METHODS Ten randomized controlled trials were selected using MEDLINE, EMBASE and CENTRAL databases until 27 September 2018. Risk ratios (RRs) with 95% confidence intervals (CIs) and risk differences (RDs) reported as incident events per 1000 person-years were calculated. RESULTS In 33,679 patients, aspirin did not significantly reduce the risk of major adverse cardiovascular outcomes (RR 0.93, 95% CI 0.87-1.00, P = 0.06; RD -0.68 incident cases per 1000 person-years (95% CI -1.54, 0.17)), cardiovascular mortality (RR 0.95, 95% CI 0.83-1.09, P = 0.49; RD 0.11 incident cases per 1000 person-years (95% CI -0.80, 1.02)), myocardial infarction (RR 0.91, 95% CI 0.75-1.11, P = 0.36; RD -0.66 incident cases per 1000 person-years (95% CI -2.07, 0.75)), or stroke (RR 0.91, 95% C, 0.76-1.10, P = 0.33; RD -0.55 incident cases per 1000 person-years (95% CI -1.57, 0.47)). There was a significantly higher risk of total bleeding associated with aspirin (RR 1.29, 95% CI 1.07-1.55, P = 0.01; RD 1.49 incident cases per 1000 person-years (95% CI 0.36, 2.61)). CONCLUSION The use of aspirin for primary prevention of cardiovascular disease in patients with diabetes mellitus increases the risk of total bleeding without reducing the risk of major adverse cardiovascular outcomes.
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Affiliation(s)
- Safi U Khan
- Department of Internal Medicine, West Virginia University, USA
| | | | - Muhammad U Khan
- Department of Internal Medicine, West Virginia University, USA
| | - Swapna Talluri
- Department of Internal Medicine, Guthrie Health System/Robert Packer Hospital, USA
| | - Farman Ali
- Department of Internal Medicine, Borgress Medical Center, USA
| | | | - Ahmad N Lone
- Department of Internal Medicine, West Virginia University, USA
| | | | - Richard A Krasuski
- Department of Cardiovascular Medicine, Duke University School of Medicine, USA
| | - Edo Kaluski
- Department of Cardiovascular Medicine, Guthrie Health System/Robert Packer Hospital, USA
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9
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Leggio M, Bendini M, Caldarone E, Lombardi M, Severi P, D’Emidio S, Stavri D, Armeni M, Bravi V, Mazza A. Low-dose aspirin for primary prevention of cardiovascular events in patients with diabetes: Benefit or risk? DIABETES & METABOLISM 2018; 44:217-225. [DOI: 10.1016/j.diabet.2017.11.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 09/05/2017] [Accepted: 11/05/2017] [Indexed: 01/13/2023]
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10
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Brotons Cuixart C, Alemán Sánchez JJ, Banegas Banegas JR, Fondón León C, Lobos-Bejarano JM, Martín Rioboó E, Navarro Pérez J, Orozco-Beltrán D, Villar Álvarez F. Recomendaciones preventivas cardiovasculares. Actualización PAPPS 2018. Aten Primaria 2018; 50 Suppl 1:4-28. [PMID: 29866357 PMCID: PMC6836998 DOI: 10.1016/s0212-6567(18)30360-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Carlos Brotons Cuixart
- Especialista en Medicina Familiar y Comunitaria, Equipo de Atención Primaria Sardenya, Barcelona
| | - José Juan Alemán Sánchez
- Especialista en Medicina Familiar y Comunitaria, Dirección General de Salud Pública, Servicio Canario de la Salud
| | - José Ramón Banegas Banegas
- Especialista en Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid
| | - Carlos Fondón León
- Especialista en Medicina Familiar y Comunitaria, Centro de Salud Colmenar de Oreja, Madrid
| | | | | | - Jorge Navarro Pérez
- Especialista en Medicina Familiar y Comunitaria, Hospital Clínico Universitario, Valencia
| | - Domingo Orozco-Beltrán
- Especialista en Medicina Familiar y Comunitaria, Unidad de Investigación CS Cabo Huertas, Departamento San Juan de Alicante, Alicante
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Tsivgoulis G, Safouris A, Kim DE, Alexandrov AV. Recent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke. J Stroke 2018; 20:145-166. [PMID: 29886715 PMCID: PMC6007302 DOI: 10.5853/jos.2018.00773] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 05/13/2018] [Accepted: 05/23/2018] [Indexed: 01/09/2023] Open
Abstract
Atherosclerosis is a major cause of ischemic stroke that can be effectively prevented with appropriate lifestyle modifications and control of cardiovascular risk factors. Medical advances in recent years along with aggressive cardiovascular risk factor modifications have resulted in decreased recurrence rates of atherosclerotic stroke. Non-statin lipid-lowering molecules have recently shown clinical benefit and are recommended for very high-risk patients to reduce their risk of stroke. Aggressive hypertension treatment is crucial to reduce atherosclerotic stroke risk. Advances in antithrombotic treatments include combinations of antiplatelets and new antiplatelet agents in the acute phase post-stroke, which carries a high risk of recurrence. Intensive medical treatment has also limited the indications for carotid interventions, especially for asymptomatic disease. Intracranial atherosclerotic disease may provoke stroke through various mechanisms; it is increasingly recognized as a cause of ischemic stroke with advanced imaging and is best managed with lifestyle modifications and medical therapy. The diagnostic search for the vulnerable culprit atherosclerotic plaque is an area of intense research, from the level of the intracranial arteries to that of the aortic arch. Ultrasonography and novel magnetic resonance imaging techniques (high-resolution vessel-wall imaging) may assist in the identification of vulnerable atherosclerotic plaques as the underlying cause in cryptogenic or misdiagnosed non-atherosclerotic ischemic stroke. Vertebrobasilar atherosclerotic disease is less common than carotid artery disease; thus, high-quality data on effective prevention strategies are scarcer. However, aggressive medical treatment is also the gold standard to reduce cerebrovascular disease located in posterior circulation.
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Affiliation(s)
- Georgios Tsivgoulis
- Second Department of Neurology, “Attikon” University Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
- Department of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA
| | - Apostolos Safouris
- Second Department of Neurology, “Attikon” University Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
- Stroke Unit, Metropolitan Hospital, Pireus, Greece
| | - Dong-Eog Kim
- Department of Neurology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Andrei V. Alexandrov
- Department of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA
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12
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Katsiki N, Purrello F, Tsioufis C, Mikhailidis DP. Cardiovascular disease prevention strategies for type 2 diabetes mellitus. Expert Opin Pharmacother 2017; 18:1243-1260. [DOI: 10.1080/14656566.2017.1351946] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Niki Katsiki
- Second Department of Propaedeutic Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Costas Tsioufis
- First Cardiology Clinic, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece
| | - Dimitri P. Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK
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13
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Kunutsor SK, Seidu S, Khunti K. Aspirin for primary prevention of cardiovascular and all-cause mortality events in diabetes: updated meta-analysis of randomized controlled trials. Diabet Med 2017; 34:316-327. [PMID: 27086572 DOI: 10.1111/dme.13133] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/11/2016] [Indexed: 12/22/2022]
Abstract
AIMS To evaluate the benefits and harms of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in people with diabetes by conducting a systematic review and meta-analysis. METHODS Randomized controlled trials of aspirin compared with placebo (or no treatment) in people with diabetes with no history of cardiovascular disease were identified from MEDLINE, EMBASE, Web of Science, the Cochrane Library and a manual search of bibliographies to November 2015. Study-specific relative risks with 95% CIs were aggregated using random effects models. RESULTS A total of 10 randomized trials were included in the review. There was a significant reduction in risk of major adverse cardiovascular events: relative risk of 0.90 (95% CI 0.81-0.99) in groups taking aspirin compared with placebo or no treatment. Limited subgroup analyses suggested that the effect of aspirin on major adverse cardiovascular events differed by baseline cardiovascular disease risk, medication compliance and sex (P for interaction for all > 0.05).There was no significant reduction in the risk of myocardial infarction, coronary heart disease, stroke, cardiovascular mortality or all-cause mortality. Aspirin significantly reduced the risk of myocardial infarction for a treatment duration of ≤ 5 years. There were differences in the effect of aspirin by dosage and treatment duration on overall stroke outcomes (P for interaction for all < 0.05). There was an increase in risk of major or gastrointestinal bleeding events, but estimates were imprecise and not significant. CONCLUSIONS The emerging data do not clearly support guidelines that encourage the use of aspirin for the primary prevention of cardiovascular disease in adults with diabetes who are at increased cardiovascular disease risk.
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Affiliation(s)
- S K Kunutsor
- School of Clinical Sciences, University of Bristol, Southmead Hospital, Southmead, UK
| | - S Seidu
- Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, UK
| | - K Khunti
- Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, UK
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14
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Howse PM, Chibrikova LN, Twells LK, Barrett BJ, Gamble JM. Safety and Efficacy of Incretin-Based Therapies in Patients With Type 2 Diabetes Mellitus and CKD: A Systematic Review and Meta-analysis. Am J Kidney Dis 2016; 68:733-742. [DOI: 10.1053/j.ajkd.2016.06.014] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 06/07/2016] [Indexed: 12/16/2022]
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Yu OHY, Suissa S. Identifying Causes for Excess Mortality in Patients With Diabetes: Closer but Not There Yet. Diabetes Care 2016; 39:1851-1853. [PMID: 27926885 DOI: 10.2337/dci16-0026] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Oriana Hoi Yun Yu
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada.,Division of Endocrinology, Jewish General Hospital, Montreal, Canada
| | - Samy Suissa
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada .,Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada
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16
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Capodanno D, Angiolillo DJ. Aspirin for Primary Cardiovascular Risk Prevention and Beyond in Diabetes Mellitus. Circulation 2016; 134:1579-1594. [PMID: 27729421 DOI: 10.1161/circulationaha.116.023164] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Accepted: 08/30/2016] [Indexed: 11/16/2022]
Abstract
Daily administration of low-dose aspirin has proved to be beneficial in preventing recurrent cardiovascular events. However, the role of aspirin for primary prevention in patients with no overt cardiovascular disease is more controversial. In fact, in lower risk patients, the modest benefit in reducing serious vascular events can be offset by the increased risk of bleeding, including intracranial and gastrointestinal hemorrhage. Diabetes mellitus has been associated with a substantially increased risk of both first and recurrent atherothrombotic events, which makes aspirin therapy of potential value in these subjects. Moving from general aspects of aspirin pharmacology and specific issues in diabetes mellitus, this article reviews the literature on the topic of aspirin for primary prevention in general, and in subjects with diabetes mellitus in particular, to culminate with arguments pro and con and a practical risk-based algorithm for aspirin initiation in daily practice.
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Affiliation(s)
- Davide Capodanno
- From Ferrarotto Hospital, University of Catania, Catania, Italy (D.C.); and University of Florida College of Medicine-Jacksonville (D.J.A.).
| | - Dominick J Angiolillo
- From Ferrarotto Hospital, University of Catania, Catania, Italy (D.C.); and University of Florida College of Medicine-Jacksonville (D.J.A.)
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17
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Kokoska LA, Wilhelm SM, Garwood CL, Berlie HD. Aspirin for primary prevention of cardiovascular disease in patients with diabetes: A meta-analysis. Diabetes Res Clin Pract 2016; 120:31-9. [PMID: 27500549 DOI: 10.1016/j.diabres.2016.07.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Revised: 05/23/2016] [Accepted: 07/24/2016] [Indexed: 11/21/2022]
Abstract
AIMS Aspirin use for primary prevention of cardiovascular disease (CVD) is controversial, especially in patients with diabetes. The objective of this meta-analysis was to evaluate aspirin's safety and efficacy for primary prevention of CVD [fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, angina, transient ischemic attack (TIA), peripheral artery disease (PAD) and revascularization] in patients with diabetes. METHODS A literature search was conducted using the terms cardiovascular disease, aspirin, diabetes mellitus to identify trials of patients with diabetes who received aspirin for primary prevention of CVD. Study sample size, and ischemic and bleeding events were extracted and analyzed using RevMan 5.2.7. RESULTS In total, 6 studies (n=10,117) met criteria. Aspirin doses ranged from 100mg every other day to 650mg daily. Follow-up ranged from 3.6 to 10.1years. In patients with diabetes, there was no difference between aspirin and placebo with respect to the risk of all cause mortality (OR 0.93, 95% CI 0.81-1.06), or individual atherosclerotic events compared to placebo. There were no differences in bleeding (OR 2.53, 95% CI 0.77-8.34), GI bleeding (OR 2.14, 95% CI 0.63-7.33) or hemorrhagic stroke rates (OR 0.90, 0.34-2.33) between groups. CONCLUSIONS It remains unclear whether aspirin may reduce the occurrence of a first atherosclerotic event or mortality in patients with diabetes. More research on this use of aspirin in patients with diabetes is required to supplement currently available research.
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Affiliation(s)
| | - Sheila M Wilhelm
- Department of Pharmacy, Harper University Hospital, Detroit Medical Center, Detroit, MI, United States; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, United States.
| | - Candice L Garwood
- Department of Pharmacy, Harper University Hospital, Detroit Medical Center, Detroit, MI, United States; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, United States.
| | - Helen D Berlie
- Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, United States; Health Centers of Detroit Medical Group, Detroit, MI, United States.
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Tazkarji B, Lam R, Lee S, Meiyappan S. Approach to preventive care in the elderly. CANADIAN FAMILY PHYSICIAN MEDECIN DE FAMILLE CANADIEN 2016; 62:717-721. [PMID: 27629666 PMCID: PMC5023341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
OBJECTIVE To guide family physicians in creating preventive screening and treatment plans for their elderly patients. SOURCES OF INFORMATION The MEDLINE database was searched for Canadian guidelines on primary health care and the elderly; guidelines or meta-analyses or practice guidelines or systematic reviews related to mass screening in those aged 80 and older and the frail elderly, limited to between 2006 and July 2016; and articles on preventive health services for the elderly related to family practice or family physicians, limited to English-language publications between 2012 and July 2016. MAIN MESSAGE Estimating life expectancy is not an easy or precise science, but frailty is an emerging concept that can help with this. The Canadian Task Force on Preventive Health Care offers cancer screening guidelines, but they are less clear for patients older than 74 years and management plans need to be individualized. Estimating remaining years of life helps guide your recommendations for preventive screening and treatment plans. Risks often increase along with an increase in frailty and comorbidity. Conversely, benefits often diminish as life expectancy decreases. Preventive management plans should take into account the patient's perspective and be mutually agreed upon. A mnemonic device for key primary care preventive areas-CCFP, short for cancer, cardiovascular disease, falls and osteoporosis, and preventive immunizations-might be useful. CONCLUSION Family physicians might find addressing the following areas helpful when considering a preventive health intervention: age, life expectancy (including concept of frailty), comorbidities and functional status, risks and benefits of screening or treatment, and values and preferences of the patient.
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Affiliation(s)
- Bachir Tazkarji
- Assistant Professor of Family Medicine at the University of Toronto in Ontario and a practising family physician with the Summerville Family Health Team in Toronto
| | - Robert Lam
- Associate Professor of Family Medicine at the University of Toronto, a practising family physician with the Toronto Western Family Health Team, and an attending physician in the Geriatric Rehabilitation Program of the University Health Network.
| | - Shawn Lee
- Family physician practising at the St Clair Medical Clinic in Toronto
| | - Soumia Meiyappan
- Research Associate in the Department of Family and Community Medicine at Toronto Western Hospital
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Tazkarji B, Lam R, Lee S, Meiyappan S. [Aborder les soins préventifs chez les aînés]. CANADIAN FAMILY PHYSICIAN MEDECIN DE FAMILLE CANADIEN 2016; 62:e508-e513. [PMID: 27629683 PMCID: PMC5023358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
OBJECTIF Guider les médecins de famille dans l'élaboration de plans de dépistage et de traitements préventifs à l'intention de leurs patients âgés. SOURCES DE L'INFORMATION Une recension a été effectuée dans la base de données MEDLINE pour trouver des lignes directrices canadiennes sur les soins de santé primaires et les personnes âgées; des lignes directrices, des méta-analyses, des guides de pratique clinique ou des révisions systématiques portant sur le dépistage de masse chez les 80 ans et plus et les aînés fragiles, se limitant à ceux publiés entre 2006 et juillet 2016; et des articles sur les services de santé préventifs à l'intention des aînés et présentant un intérêt pour la pratique familiale ou les médecins de famille, limités à ceux publiés en anglais entre 2012 et juillet 2016. MESSAGE PRINCIPAL L'estimation de l'espérance de vie n'est pas une science facile ou précise, mais la fragilité est un concept émergent susceptible d'être utile à cet égard. Le Groupe d'étude canadien sur les soins de santé préventifs propose des lignes directrices sur le dépistage du cancer, mais elles sont moins précises en ce qui concerne les patients de plus de 74 ans et il faut donc individualiser les plans de prise en charge. L'estimation des années de vie qui restent aide à orienter vos recommandations concernant les plans de dépistage et de traitements préventifs. Les risques augmentent souvent proportionnellement avec la fragilité et la comorbidité. D'autre part, les bienfaits diminuent souvent à mesure que l'espérance de vie raccourcit. Les plans de prise en charge préventive devraient tenir compte des points de vue du patient et être convenus d'un commun accord. Un moyen mnémonique pour se rappeler des principaux domaines de prévention en soins primaires - CCMF, abréviation pour cancer, cardiovasculaire, mauvais équilibre, chute et ostéoporose, fiche de vaccinations préventives - pourrait se révéler utile. CONCLUSION Les médecins de famille pourraient trouver utile de tenir compte des éléments suivants lorsqu'ils envisagent une intervention en soins préventifs : l'âge, l'espérance de vie (incluant le concept de la fragilité), la comorbidité et l'état fonctionnel, les risques et les bienfaits du dépistage ou du traitement, de même que les valeurs et les préférences du patient.
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Affiliation(s)
- Bachir Tazkarji
- Professeur adjoint de médecine familiale à l'Université de Toronto, en Ontario, et médecin de famille actif au sein de l'Équipe de santé familiale Summerville à Toronto
| | - Robert Lam
- Professeur agrégé de médecine familiale à l'Université de Toronto, médecin de famille actif au sein de l'Équipe de santé familiale Toronto Western et médecin traitant au programme de réadaptation gériatrique de l'University Health Network.
| | - Shawn Lee
- Médecin de famille actif à la St Clair Medical Clinic à Toronto
| | - Soumia Meiyappan
- Associée de recherche au Département de médecine familiale et communautaire du Toronto Western Hospital
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Karmali KN, Lloyd-Jones DM, Berendsen M, Goff DC, Sanghavi DM, Brown N, Korenovska L, Huffman MD. Drugs for Primary Prevention of Atherosclerotic Cardiovascular Disease: An Overview of Systematic Reviews. JAMA Cardiol 2016; 1:341-9. [PMID: 27438118 PMCID: PMC5053397 DOI: 10.1001/jamacardio.2016.0218] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
IMPORTANCE The Million Hearts initiative emphasizes ABCS (aspirin for high-risk patients, blood pressure [BP] control, cholesterol level management, and smoking cessation). Evidence of the effects of drugs used to achieve ABCS has not been synthesized comprehensively in the prevention of primary atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE To compare the efficacy and safety of aspirin, BP-lowering therapy, statins, and tobacco cessation drugs for fatal and nonfatal ASCVD outcomes in primary ASCVD prevention. EVIDENCE REVIEW Structured search of the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), MEDLINE, EMBASE, and PROSPERO International Prospective Systematic Review Trial Register to identify systematic reviews published from January 1, 2005, to June 17, 2015, that reported the effect of aspirin, BP-lowering therapy, statin, or tobacco cessation drugs on ASCVD events in individuals without prevalent ASCVD. Additional studies were identified by searching the reference lists of included systematic reviews, meta-analyses, and health technology assessment reports. Reviews were selected according to predefined criteria and appraised for methodologic quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool (range, 0-11). Studies were independently reviewed for key participant and intervention characteristics. Outcomes that were meta-analyzed in each included review were extracted. Qualitative synthesis was performed, and data were analyzed from July 2 to August 13, 2015. FINDINGS From a total of 1967 reports, 35 systematic reviews of randomized clinical trials were identified, including 15 reviews of aspirin, 4 reviews of BP-lowering therapy, 12 reviews of statins, and 4 reviews of tobacco cessation drugs. Methodologic quality varied, but 30 reviews had AMSTAR ratings of 5 or higher. Compared with placebo, aspirin (relative risk [RR], 0.90; 95% CI, 0.85-0.96) and statins (RR, 0.75; 95% CI, 0.70-0.81) reduced the risk for ASCVD. Compared with placebo, BP-lowering therapy reduced the risk for coronary heart disease (RR, 0.84; 95% CI, 0.79-0.90) and stroke (RR, 0.64; 95% CI, 0.56-0.73). Tobacco cessation drugs increased the odds of continued abstinence at 6 months (odds ratio range, 1.82 [95% CI, 1.60-2.06] to 2.88 [95% CI, 2.40-3.47]), but the direct effects on ASCVD were poorly reported. Aspirin increased the risk for major bleeding (RR, 1.54; 95% CI, 1.30-1.82), and statins did not increase overall risk for adverse effects (RR, 1.00; 95% CI, 0.97-1.03). Adverse effects of BP-lowering therapy and tobacco cessation drugs were poorly reported. CONCLUSIONS AND RELEVANCE This overview demonstrates high-quality evidence to support aspirin, BP-lowering therapy, and statins for primary ASCVD prevention and tobacco cessation drugs for smoking cessation. Treatment effects of each drug can be used to enrich discussions between health care professionals and patients in primary ASCVD prevention.
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Affiliation(s)
- Kunal N. Karmali
- Departments of Preventive Medicine and Medicine-Cardiology, Northwestern University Feinberg School of Medicine, Chicago, USA
| | - Donald M. Lloyd-Jones
- Departments of Preventive Medicine and Medicine-Cardiology, Northwestern University Feinberg School of Medicine, Chicago, USA
| | - Mark Berendsen
- Galter Health Sciences Library, Northwestern University Feinberg School of Medicine, Chicago, USA
| | - David C. Goff
- Colorado School of Public Health, University of Colorado Anschutz Medical Center, Colorado, USA
| | | | - Nina Brown
- Center for Medicare and Medicaid Services, Baltimore, Maryland
| | | | - Mark D. Huffman
- Departments of Preventive Medicine and Medicine-Cardiology, Northwestern University Feinberg School of Medicine, Chicago, USA
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Scheen AJ. Reduction in cardiovascular and all-cause mortality in the EMPA-REG OUTCOME trial: A critical analysis. DIABETES & METABOLISM 2016; 42:71-6. [DOI: 10.1016/j.diabet.2015.12.005] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 12/26/2015] [Indexed: 01/15/2023]
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Abstract
Diabetes imparts a substantial increased risk for cardiovascular disease-related mortality and morbidity. Because of this, current medical guidelines recommend prophylactic treatment with once-daily, low-dose aspirin (acetylsalicylic acid) for primary and secondary prevention of cardiovascular (CV) events in high-risk patients. However, only modest reductions in CV events and mortality have been observed with once-daily aspirin treatment in patients with diabetes, including patients with a previous CV event, perhaps because of disparity between aspirin pharmacokinetics and diabetes-related platelet abnormalities. Once-daily aspirin irreversibly inactivates platelets for only a short duration (acetylsalicylic acid half-life, approximately 15-20 minutes), after which time newly generated, active platelets enter the circulation and weaken aspirin's effect. Platelets from patients with diabetes are more reactive and are turned over more rapidly than platelets from normal individuals; the short inhibitory window provided by once-daily aspirin may therefore be insufficient to provide 24-h protection against CV events. Alternative conventional aspirin regimens (e.g. higher daily dose, twice-daily dosing, combination with clopidogrel) and newer formulations (e.g. 24-h, extended-release) have been proposed to overcome the apparent limited efficacy of conventional aspirin in patients with diabetes; however, tolerability concerns and limited clinical efficacy data need to be taken into account when considering the use of such regimens.
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Nansseu JRN, Noubiap JJN. Aspirin for primary prevention of cardiovascular disease. Thromb J 2015; 13:38. [PMID: 26640414 PMCID: PMC4669607 DOI: 10.1186/s12959-015-0068-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Accepted: 08/29/2015] [Indexed: 01/27/2023] Open
Abstract
Although aspirin has a well-established role in preventing adverse events in patients with known cardiovascular disease (CVD), its benefit in patients without a history of CVD remains under scrutiny. Current data have provided insight into the risks of aspirin use, particularly bleeding, compared with its benefits in primary CVD prevention. Although aspirin is inexpensive and widely available, especially in developing countries, there is lack of evidence that the benefits outweigh the adverse events with continuous aspirin use in primary CVD prevention. Therefore, the decision to initiate aspirin therapy should be an individual clinical judgment that weighs the absolute benefit in reducing the risk of a first cardiovascular event against the absolute risk of major bleeding, and tailored to the patient's CVD risk. This risk must be calculated, based on accurate and cost-benefit locally developed risk assessment tools, the most discriminating threshold be identified. Additionally, patients preferences should be taken into account when making the decision to initiate aspirin therapy in primary prevention of CVD or not. Physicians should continuously be trained to calculate their patients CVD risk, and concomitant strategies be emphasized.
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Affiliation(s)
- Jobert Richie N Nansseu
- Department of Public Health, Faculty of Medicine and Biomedical Sciences of the University of Yaoundé I, PO Box 1364, Yaoundé, Cameroon ; Sickle Cell Disease Unit, Mother and Child Centre of the Chantal Biya Foundation, Yaoundé, Cameroon
| | - Jean Jacques N Noubiap
- Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa ; Medical Diagnostic Centre, Yaoundé, Cameroon
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Tassone EJ, Perticone M, Sciacqua A, Mafrici SF, Settino C, Malara N, Mollace V, Sesti G, Perticone F. Low dose of acetylsalicylic acid and oxidative stress-mediated endothelial dysfunction in diabetes: a short-term evaluation. Acta Diabetol 2015; 52:249-56. [PMID: 25091345 PMCID: PMC4374120 DOI: 10.1007/s00592-014-0629-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Accepted: 07/02/2014] [Indexed: 01/03/2023]
Abstract
Current guidelines suggest the use of low doses of acetylsalicylic acid (ASA) for patients with diabetes mellitus (DM) in primary prevention. However, the evidences demonstrating the beneficial effect of ASA in primary prevention are conflicting. In this pilot study, we evaluated in a group of diabetic patients, in primary prevention, the impact of ASA treatment on oxidative stress and vascular function. We enrolled 22 newly diagnosed diabetic patients, without any previous clinical evidence of cardiovascular disease, to receive, in primary prevention, ASA (100 mg/daily). We tested, in basal condition, after 4 weeks of ASA administration and after 4 weeks of pharmacological washout, the impact of ASA treatment on endothelial function, assessed by a semipletysmographic method, measuring the main oxidative stress parameters related to it. As expected, after 4 weeks of treatment, ASA induced a significant reduction of plasma thromboxane-A2, as a consequence of cyclooxygenase-1 inhibition. By contrast, ASA significantly increased the plasma and urine 8-iso-PGF2α, a well-known prothrombotic molecule, parallel to an increase of plasma NOX2 levels. The enhancement of this oxidative pathway is associated with a significant impairment of endothelial vasodilation, assessed by reactive hyperemia index (RHI). The pharmacological washout reverted all parameters to basal condition. Our findings suggest that ASA utilization for primary prevention in diabetic patients causes a significant increase of oxidative stress burden impairing the vascular function. Present data, if confirmed on a larger population, could permanently discourage the use of the ASA for the primary prevention in patients with DM.
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Affiliation(s)
- Eliezer Joseph Tassone
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
| | - Maria Perticone
- Department of Clinical and Experimental Medicine, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
| | - Simona Fortunata Mafrici
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
| | - Chiara Settino
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
| | - Natalia Malara
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
- Interregional Research Center for Food Safety and Health (IRC-FSH), Catanzaro, Italy
| | - Vincenzo Mollace
- IRCCS San Raffaele, Rome, Italy
- Department of Health Science, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
| | - Giorgio Sesti
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
| | - Francesco Perticone
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
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Brotons C, Benamouzig R, Filipiak KJ, Limmroth V, Borghi C. A systematic review of aspirin in primary prevention: is it time for a new approach? Am J Cardiovasc Drugs 2015; 15:113-33. [PMID: 25502483 PMCID: PMC4383813 DOI: 10.1007/s40256-014-0100-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background and Objectives While evidence in support of aspirin use in secondary prevention is well documented, the role of aspirin in primary prevention remains unclear. We conducted a systematic literature review to evaluate aspirin use in cardiovascular disease (CVD) and cancer primary prevention, and consider whether aspirin’s role is set to become more clearly defined based on past and prospective studies. Data Sources Utilizing PubMed, the reviewers identified appropriate Medical Subject Headings (MeSH) terms to establish CVD-based studies, cancer-based studies, and studies on adherence. Study Eligibility Criteria Date restrictions of May 31, 2008 to May 31, 2013 were applied to capture the most robust meta-analyses and randomized controlled trials. Websites of relevant EU and US scientific societies were used to identify the key guidelines for aspirin use in primary prevention of CVD, and ClinicalTrials.gov was used to establish future or ongoing trials. Results Evidence in support of aspirin prophylaxis is conflicting, though some meta-analyses have underlined potential benefit in reducing cardiovascular events. Despite this apparent benefit, bleeding risk with aspirin is consistently higher versus control, and remains a concern. A reduction of cancer incidence and mortality after a least 3 and 5 years treatment, respectively, is also apparent with aspirin. Conclusion Available data on aspirin in primary prevention suggest a modest benefit for patients at high risk of CVD, and a promising benefit for those at risk of cancer. Future studies should help to elucidate whether the benefit of aspirin outweighs risk in appropriate patient groups.
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Affiliation(s)
- Carlos Brotons
- Research Unit, Sardenya Primary Health Care Center, Biomedical Research Institute Sant Pau. Teaching Unit of Family Medicine ACEBA, Sardenya 466, 08025, Barcelona, Spain,
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Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, Creager MA, Eckel RH, Elkind MSV, Fornage M, Goldstein LB, Greenberg SM, Horvath SE, Iadecola C, Jauch EC, Moore WS, Wilson JA. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:3754-832. [PMID: 25355838 PMCID: PMC5020564 DOI: 10.1161/str.0000000000000046] [Citation(s) in RCA: 1044] [Impact Index Per Article: 94.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of stroke among individuals who have not previously experienced a stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches to atherosclerotic disease of the cervicocephalic circulation, and antithrombotic treatments for preventing thrombotic and thromboembolic stroke. Further recommendations are provided for genetic and pharmacogenetic testing and for the prevention of stroke in a variety of other specific circumstances, including sickle cell disease and patent foramen ovale.
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Xie M, Shan Z, Zhang Y, Chen S, Yang W, Bao W, Rong Y, Yu X, Hu FB, Liu L. Aspirin for primary prevention of cardiovascular events: meta-analysis of randomized controlled trials and subgroup analysis by sex and diabetes status. PLoS One 2014; 9:e90286. [PMID: 25360605 PMCID: PMC4215843 DOI: 10.1371/journal.pone.0090286] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Accepted: 01/28/2014] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status. METHODS We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12. RESULTS Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85-0.95), myocardial infarction (0.86; 0.75-0.93), ischemic stroke (0.86; 0.75-0.98) and all-cause mortality (0.94; 0.89-0.99). There were also increases in hemorrhagic stroke (1.34; 1.01-1.79) and major bleeding (1.55; 1.35-1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59-0.85) and ischemic stroke among women (0.77; 0.63-0.93). Aspirin use was associated with a reduction (0.65; 0.51-0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day). CONCLUSIONS The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials.
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Affiliation(s)
- Manling Xie
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Zhilei Shan
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Yan Zhang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Sijing Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Wei Yang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Wei Bao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Ying Rong
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Xuefeng Yu
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Frank B. Hu
- Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
- * E-mail: (LL); (FBH)
| | - Liegang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
- * E-mail: (LL); (FBH)
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Sirois C, Moisan J, Poirier P, Grégoire JP. Myocardial infarction and gastro-intestinal bleeding risks associated with aspirin use among elderly individuals with type 2 diabetes. Ann Med 2014; 46:335-40. [PMID: 24785356 DOI: 10.3109/07853890.2014.902636] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
INTRODUCTION The benefit of aspirin in primary prevention of myocardial infarction and the associated gastro-intestinal bleeding risks have not been well established in the elderly population with diabetes. METHODS Using Quebec administrative databases, we conducted two nested case-control analyses within a cohort of individuals aged ≥ 66 years newly treated with an oral antidiabetes drug between 1998 and 2003. The 28,067 individuals had no cardiovascular disease recorded in the database in the year prior cohort entry. They had not used prescribed aspirin, antiplatelet, or anticoagulant drugs, and were not hospitalized for gastro-intestinal bleeding in the year prior cohort entry. The odds of myocardial infarction and gastro-intestinal bleedings were compared between individuals who were current, past, or non-users of aspirin. RESULTS There were 1101 (3.9%) cases of myocardial infarction. Compared to non-users, neither aspirin users (OR 0.89; 95% CI 0.71-1.13) nor aspirin past users (0.81; 0.62-1.06) showed a statistically significant lower risk of myocardial infarction. There were 373 (1.3%) cases of gastro-intestinal bleeding. Current users of aspirin had about a 2-fold greater risk of gastro-intestinal bleeding compared to non-users (2.19; 1.53-3.13). CONCLUSIONS Our results suggest that individual assessment of bleeding risk and cardiovascular risk is mandatory among elderly people with diabetes before introducing aspirin therapy.
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Lopez LR, Guyer KE, Torre IGDL, Pitts KR, Matsuura E, Ames PRJ. Platelet thromboxane (11-dehydro-Thromboxane B 2) and aspirin response in patients with diabetes and coronary artery disease. World J Diabetes 2014; 5:115-127. [PMID: 24748925 PMCID: PMC3990310 DOI: 10.4239/wjd.v5.i2.115] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Revised: 02/25/2014] [Accepted: 03/12/2014] [Indexed: 02/05/2023] Open
Abstract
Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes (DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2 (11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls (P = 0.024): female subjects (DM and controls) had 50.9% higher baseline 11dhTxB2 than males (P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM (71.7%) and controls (75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders (ASA “resistant”) in DM than in controls (14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome (ACS) patients was 28.6 and 28.7%, in spite of a significant (81.6%) inhibition of urinary 11dhTxB2 (P < 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.
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Szuszkiewicz-Garcia MM, Davidson JA. Cardiovascular disease in diabetes mellitus: risk factors and medical therapy. Endocrinol Metab Clin North Am 2014; 43:25-40. [PMID: 24582090 DOI: 10.1016/j.ecl.2013.09.001] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Cardiovascular disease is a serious complication of diabetes mellitus. In the last 2 decades, great strides have been made in reducing microvascular complications in patients with diabetes through improving glycemic control. Decreasing rates of cardiovascular events have proved to be more difficult than simply intensifying the management of hyperglycemia. A tremendous effort has been made to deepen understanding of cardiovascular disease in diabetes and to formulate the best treatment approach. This review summarizes the current state of knowledge and discusses areas of uncertainty in the care of patients with diabetes who are at risk for cardiovascular disease.
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Affiliation(s)
- Magdalene M Szuszkiewicz-Garcia
- Division of Endocrinology and Metabolism, Center for Human Nutrition, Department of Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8857, USA.
| | - Jaime A Davidson
- Division of Endocrinology, Diabetes and Metabolism, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard K5.246, Dallas, TX 75390, USA
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Lorber D. Importance of cardiovascular disease risk management in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes 2014; 7:169-83. [PMID: 24920930 PMCID: PMC4043722 DOI: 10.2147/dmso.s61438] [Citation(s) in RCA: 117] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is commonly accompanied by other cardiovascular disease (CVD) risk factors, such as hypertension, obesity, and dyslipidemia. Furthermore, CVD is the most common cause of death in people with T2DM. It is therefore of critical importance to minimize the risk of macrovascular complications by carefully managing modifiable CVD risk factors in patients with T2DM. Therapeutic strategies should include lifestyle and pharmacological interventions targeting hyperglycemia, hypertension, dyslipidemia, obesity, cigarette smoking, physical inactivity, and prothrombotic factors. This article discusses the impact of modifying these CVD risk factors in the context of T2DM; the clinical evidence is summarized, and current guidelines are also discussed. The cardiovascular benefits of smoking cessation, increasing physical activity, and reducing low-density lipoprotein cholesterol and blood pressure are well established. For aspirin therapy, any cardiovascular benefits must be balanced against the associated bleeding risk, with current evidence supporting this strategy only in certain patients who are at increased CVD risk. Although overweight, obesity, and hyperglycemia are clearly associated with increased cardiovascular risk, the effect of their modification on this risk is less well defined by available clinical trial evidence. However, for glucose-lowering drugs, further evidence is expected from several ongoing cardiovascular outcome trials. Taken together, the evidence highlights the value of early intervention and targeting multiple risk factors with both lifestyle and pharmacological strategies to give the best chance of reducing macrovascular complications in the long term.
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Affiliation(s)
- Daniel Lorber
- Division of Endocrinology, New York Hospital Queens, Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA
- Correspondence: Daniel Lorber, Division of Endocrinology, New York Hospital Queens, 5945 161st Street, Flushing, New York, NY 11365, USA, Tel +1 718 762 3111, Fax +1 718 353 6315, Email
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Sutcliffe P, Connock M, Gurung T, Freeman K, Johnson S, Ngianga-Bakwin K, Grove A, Gurung B, Morrow S, Stranges S, Clarke A. Aspirin in primary prevention of cardiovascular disease and cancer: a systematic review of the balance of evidence from reviews of randomized trials. PLoS One 2013; 8:e81970. [PMID: 24339983 PMCID: PMC3855368 DOI: 10.1371/journal.pone.0081970] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2013] [Accepted: 10/18/2013] [Indexed: 12/21/2022] Open
Abstract
Background Aspirin has been recommended for primary prevention of cardiovascular disease (CVD) and cancer, but overall benefits are unclear. We aimed to use novel methods to re-evaluate the balance of benefits and harms of aspirin using evidence from randomised controlled trials, systematic reviews and meta-analyses. Methods and Findings Data sources included ten electronic bibliographic databases, contact with experts, and scrutiny of reference lists of included studies. Searches were undertaken in September 2012 and restricted to publications since 2008. Of 2,572 potentially relevant papers 27 met the inclusion criteria. Meta-analysis of control arms to estimate event rates, modelling of all-cause mortality and L'Abbé plots to estimate heterogeneity were undertaken. Absolute benefits and harms were low: 60-84 major CVD events and 34-36 colorectal cancer deaths per 100,000 person-years were averted, whereas 46-49 major bleeds and 68-117 gastrointestinal bleeds were incurred. Reductions in all-cause mortality were minor and uncertain (Hazard Ratio 0.96; 95% CI: 0.90-1.02 at 20 years, Relative Risk [RR] 0.94, 95% CI: 0.88-1.00 at 8 years); there was a non-significant change in total CVD (RR 0.85, 95% CI: 0.69-1.06) and change in total cancer mortality ranged from 0.76 (95% CI: 0.66-0.88) to 0.93 (95% CI: 0.84-1.03) depending on follow-up time and studies included. Risks were increased by 37% for gastrointestinal bleeds (RR 1.37, 95% CI: 1.15-1.62), 54%-66% for major bleeds (Rate Ratio from IPD analysis 1.54, 95% CI: 1.30-1.82, and RR 1.62, 95% CI: 1.31-2.00), and 32%-38% for haemorrhagic stroke (Rate Ratio from IPD analysis 1.32; 95% CI: 1.00-1.74; RR 1.38; 95% CI: 1.01-1.82). Conclusions Findings indicate small absolute effects of aspirin relative to the burden of these diseases. When aspirin is used for primary prevention of CVD the absolute harms exceed the benefits. Estimates of cancer benefit rely on selective retrospective re-analysis of RCTs and more information is needed.
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Affiliation(s)
- Paul Sutcliffe
- Warwick Medical School, University of Warwick, Coventry, Warwickshire, England
| | - Martin Connock
- Warwick Medical School, University of Warwick, Coventry, Warwickshire, England
| | - Tara Gurung
- Warwick Medical School, University of Warwick, Coventry, Warwickshire, England
| | - Karoline Freeman
- Warwick Medical School, University of Warwick, Coventry, Warwickshire, England
| | - Samantha Johnson
- Warwick Medical School, University of Warwick, Coventry, Warwickshire, England
| | | | - Amy Grove
- Warwick Medical School, University of Warwick, Coventry, Warwickshire, England
| | - Binu Gurung
- Warwick Medical School, University of Warwick, Coventry, Warwickshire, England
| | - Sarah Morrow
- Oxford Medical School, University of Oxford, Oxford, England
| | - Saverio Stranges
- Warwick Medical School, University of Warwick, Coventry, Warwickshire, England
| | - Aileen Clarke
- Warwick Medical School, University of Warwick, Coventry, Warwickshire, England
- * E mail:
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Takahashi Y, Nishida Y, Nakayama T, Asai S. Comparative effect of clopidogrel and aspirin versus aspirin alone on laboratory parameters: a retrospective, observational, cohort study. Cardiovasc Diabetol 2013; 12:87. [PMID: 23767412 PMCID: PMC3687565 DOI: 10.1186/1475-2840-12-87] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2013] [Accepted: 06/09/2013] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Combination therapy of clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in patients in routine clinical practice. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters using a clinical database. METHODS We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between November 2004 and April 2011, to identify cohorts of new users (n = 159) of clopidogrel (75 mg/day) plus aspirin (100 mg/day) and new users (n = 834) of aspirin alone (100 mg/day). We used a multivariable regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between settings, and compare the mean changes in serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase and hematological parameters, including hemoglobin level, hematocrit, and white blood cell (WBC), red blood cell and platelet counts up to two months after the start of study drug administration. RESULTS After adjustment, the reduction of WBC count in clopidogrel plus aspirin users was significantly greater than that in aspirin alone users. All other tests showed no statistically significant difference in the mean change from baseline to during the exposure period between clopidogrel plus aspirin users and aspirin alone users. The combination of clopidogrel and aspirin increased the risk of gastrointestinal bleeding compared with aspirin alone, with a relative risk ranging from 2.06 (95% CI, 1.02 to 4.13; p = 0.043) for the multivariate model and 2.61 (95% CI, 1.18 to 5.80; p = 0.0184) for propensity adjustment. CONCLUSION Our findings suggested that hematological adverse effects may be greater with combination therapy of clopidogrel plus aspirin than with aspirin monotherapy.
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Schnell O, Erbach M, Hummel M. Primary and secondary prevention of cardiovascular disease in diabetes with aspirin. Diab Vasc Dis Res 2012; 9:245-55. [PMID: 22508698 DOI: 10.1177/1479164112441486] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Diabetes is associated with an increased cardiovascular risk. The role for aspirin in diabetes is of high clinical interest. Guidelines recommend that primary prevention of cardiovascular disease (CVD) in diabetes with aspirin should be based on the individual risk for CVD. New mechanistic studies suggest that enhanced platelet turnover may partly contribute to the fact the primary prevention studies found unequivocal results in diabetes. There is initial evidence that a potential future modification of dosages in diabetes may counteract the enhancement in platelet turnover in diabetes. The use of aspirin in diabetic patients for secondary prevention of CVD is supported by key evidence. The aim of the review is to present recent studies on aspirin for prevention of CVD in diabetes and to highlight its role also in view of new mechanistic and clinical studies with aspirin. Novel aspects of aspirin, e.g. its potential role for the prevention of cancer, are also presented.
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Affiliation(s)
- Oliver Schnell
- Diabetes Research Group, Helmholtz Centre Munich, Neuherberg, Germany.
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Abbate R, Mannucci E, Cioni G, Fatini C, Marcucci R. Diabetes and sex: from pathophysiology to personalized medicine. Intern Emerg Med 2012; 7 Suppl 3:S215-9. [PMID: 23073860 DOI: 10.1007/s11739-012-0804-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The prevalence and incidence of diabetes is similar in the two sexes but the long-term impact of diabetes on vascular and non-vascular complications is more gender specific. Men, in comparison with women, seem to be at higher risk for micro-vascular complications, such as severe retinopathy and nephropathy. On the other hand, the impact of diabetes on the risk of major cardiovascular events is different in women in comparison with men. Both type 1 and type 2 diabetes are associated with a significant increase in the incidence of bone fractures. Although this phenomenon is present in both sexes, its impact is greater in women, due to the higher baseline incidence of fractures. Diabetes negatively affects mood, leading to an increased risk of depressive disorders, due to the burden and side effects of therapy, together with the fear of complications. This phenomenon can be more evident in women, who are at greater risk of depressive disorders. Non-pharmacological treatments (i.e. diet and exercise), which are the backbone of therapy for type 2 diabetes, do not differ across genders. On the other hand, some drugs could have diverse profiles of action in women and in men. In relation to diabetes, the sex-related difference in platelet activity and platelet inhibitory response to anti-aggregating therapy, reported in the general population, was observed also in diabetic women.
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Affiliation(s)
- Rosanna Abbate
- Department of Medical and Surgical Critical Care, University of Florence, SOD Atherothrombotic Diseases, AOU Careggi, Viale Morgagni, 85, 50134, Florence, Italy
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Sirois C, Couture J, Grégoire JP. Acetylsalicylic acid for primary prevention of cardiovascular diseases in older patients with diabetes: do the benefits overcome the risks? Ther Adv Drug Saf 2012; 3:213-26. [PMID: 25083237 PMCID: PMC4110868 DOI: 10.1177/2042098612451267] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Cardiovascular diseases (CVDs) represent a huge health burden for older patients with diabetes. Acetylsalicylic acid (ASA) has long been used as a cardioprotective agent in primary and secondary prevention of CVD. However, there are important issues regarding the benefits and risks of ASA therapy in primary prevention of CVDs, for the older group in general and for individuals of all ages with diabetes. In this review, we summarize the benefits and risks related to ASA therapy by outlining the evidence for older patients and for patients with diabetes. There appear to be significant gaps in knowledge. The balance of benefits and risks is not well defined but ASA treatment seems to be unfavorable in many older patients.
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Affiliation(s)
- Caroline Sirois
- UQAR, Campus de Lévis 1595, boulevard Alphonse-Desjardins Lévis (Québec) Canada G6V 0A6
| | - Julie Couture
- Centre Hospitalier Universitaire de Québec - CHUL, Québec, Canada
| | - Jean-Pierre Grégoire
- Faculty of Pharmacy, Laval University, Quebec; and Centre de Recherche FRSQ du CHA, Universitaire de Québec - URESP, Québec, Canada
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Nemerovski CW, Salinitri FD, Morbitzer KA, Moser LR. Aspirin for primary prevention of cardiovascular disease events. Pharmacotherapy 2012; 32:1020-35. [PMID: 23019080 DOI: 10.1002/phar.1127] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Aspirin has been used for the prevention and treatment of cardiovascular disease (CVD) for several decades. The efficacy of aspirin for secondary prevention of cardiovascular disease is well established, but the clinical benefit of aspirin for primary prevention of CVD is less clear. The primary literature suggests that aspirin may provide a reduction in CVD events, but the absolute benefit is small and accompanied by an increase in bleeding. For aspirin to be beneficial for an individual patient, the risk of a future CVD event must be large enough to outweigh the risk of bleeding. The estimation of CVD risk is multifaceted and can involve numerous risk scores and assessments of concomitant comorbidities that confer additional CVD risk. Numerous guidelines provide recommendations for the use of aspirin for primary prevention, but they often contradict one another despite being based on the same clinical trials. Additional literature suggests that the presence of comorbidities that increase CVD risk, such as diabetes mellitus, asymptomatic peripheral arterial disease, or chronic kidney disease, does not ensure that aspirin therapy will be beneficial. Ongoing clinical trials may provide additional insight, but until more data are available, an individualized assessment of CVD risk with careful evaluation of risk and benefit should be performed before recommending aspirin therapy for primary prevention of CVD.
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Affiliation(s)
- Carrie W Nemerovski
- Department of Pharmacy Services, Henry Ford Hospital, Detroit, Michigan 48202, USA.
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Tricco AC, Alateeq A, Tashkandi M, Mamdani M, Al-Omran M, Straus SE. Histamine H2 receptor antagonists for decreasing gastrointestinal harms in adults using acetylsalicylic acid: systematic review and meta-analysis. OPEN MEDICINE : A PEER-REVIEWED, INDEPENDENT, OPEN-ACCESS JOURNAL 2012; 6:e109-17. [PMID: 23687524 PMCID: PMC3654505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2012] [Revised: 05/24/2012] [Accepted: 05/24/2012] [Indexed: 11/23/2022]
Abstract
BACKGROUND It is unclear if histamine H2 receptor antagonists (H2 blockers) prevent a variety of gastrointestinal harms among patients taking acetylsalicylic acid (ASA) over long periods. METHODS Electronic databases (e.g., MEDLINE, Embase and Cochrane Central Register of Controlled Trials; from inception to November 2010) and reference lists of retrieved articles were searched. Randomized placebo-controlled trials (RCTs) assessing the efficacy of H2 blockers in reducing gastrointestinal harms (bleeding, ulcers) among adults taking ASA for 2 weeks or longer were included. Two reviewers independently abstracted study and patient characteristics and appraised study quality using the Cochrane risk-of-bias tool. Peto odds ratio (OR) meta-analysis was performed, 95% confidence intervals (CIs) were calculated, and statistical heterogeneity was assessed using the I (2) and χ(2) statistics. RESULTS Six RCTs (4 major publications and 2 companion reports) with a total of 498 participants (healthy volunteers or patients with arthritis, cardiovascular or cerebrovascular disease, or diabetes mellitus) were included. One trial adequately reported allocation concealment and sequence generation, with the other 3 trials being judged as unclear for both aspects. In one RCT, no statistically significant differences for gastrointestinal hemorrhage requiring admission to hospital (p = 0.14) or blood transfusion (p = 0.29) were observed between the group receiving concomitant famotidine and ASA and the group receiving concomitant placebo and ASA. After a median of 8 weeks' follow-up, H2 blockers were more effective than placebo in reducing gastrointestinal hemorrhage (2 RCTs, total of 447 patients, OR 0.07, 95% CI 0.02-0.23) and peptic ulcers (3 RCTs, total of 465 patients, OR 0.21, 95% CI 0.12-0.36) among patients taking ASA for 2 weeks or longer. Despite substantial clinical heterogeneity across the studies, including types of H2 blockers, dosing of ASA and underlying conditions, no statistical heterogeneity was observed. INTERPRETATION H2 blockers reduced gastrointestinal harm among patients taking ASA for 2 weeks or longer. These results should be interpreted with caution, because of the small number of studies identified for inclusion.
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Affiliation(s)
- Andrea C Tricco
- St. Michael’s Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada
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Magri CJ, Fava S. Should diabetes still be considered a coronary artery disease equivalent? J Cardiovasc Med (Hagerstown) 2012; 13:760-5. [PMID: 22885535 DOI: 10.2459/jcm.0b013e3283577295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Diabetes is well established as a cardiovascular risk factor and is currently regarded as a coronary artery disease equivalent. However, some recent data have contradicted the concept. We review the currently available data and usefulness or otherwise of this concept. While the concept of coronary artery disease equivalence has served to highlight the importance of diabetes as a risk factor, it has a number of problems. We propose that it would be more useful to consider diabetes as a myocardial infarction risk equivalent. This is not only more precise and in line with the literature but also conveys better the message that patients with diabetes and one or more previous myocardial infarction(s) are at even higher risk.
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Affiliation(s)
- Caroline J Magri
- Department of Cardiology, Mater Dei Hospital, University of Malta, Malta
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Han JY, Choi DH, Choi SW, Kim BB, Ki YJ, Chung JW, Koh YY, Chang KS, Hong SP. Stroke or coronary artery disease prediction from mean platelet volume in patients with type 2 diabetes mellitus. Platelets 2012; 24:401-6. [DOI: 10.3109/09537104.2012.710858] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Ames PRJ, Batuca JR, Muncy IJ, De La Torre IG, Pascoe-Gonzales S, Guyer K, Matsuura E, Lopez LR. Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus. Thromb Res 2012; 130:350-4. [PMID: 22521214 DOI: 10.1016/j.thromres.2012.03.025] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2011] [Revised: 03/06/2012] [Accepted: 03/27/2012] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on platelet activation, thromboxane generation, oxidative stress and anti-oxidant biomarkers was studied in type 2 diabetes mellitus (DM). MATERIAL AND METHODS Baseline and post-ASA samples (100/325 mg x 7 days) were obtained from 75 DM patients and 86 healthy controls for urinary 11-dehydro-thromboxane B2 (11 dhTxB2), 8-iso-prostaglandin-F2α (8-isoPGF2α) and serum sP-Selectin, nitrite (NO(2)(-)), nitrate (NO(3)(-)) and paraoxonase 1 (PON1) activity. RESULTS Compared to baseline controls, baseline DM had higher mean levels of 11 dhTxB2 (3,665 ± 2,465 vs 2,450 ± 1,572 pg/mg creatinine, p=0.002), 8-isoPGF2α (1,457 ± 543 vs 1,009 ± 412 pg/mg creatinine, p<0.0001), NO(2)(-) (11.8 ± 7.3 vs 4.8 ± 5.3 μM, p<0.0001), NO(3)(-) (50.4 ± 39.3 vs 20.9 ± 16.7 μM, p<0.0001) and sP-Selectin (120.8 ± 56.7 vs 93.0 ± 26.1 ng/mL, p=0.02), and the same held for post-ASA levels (p<0.0001). ASA demonstrated no effect on 8-isoPGF2α, NO(2)(-), NO(3)(-), sP-Selectin or PON1 activity in either DM or controls. Post ASA inhibition of urinary 11 dhTxB2 was 71.5% in DM and 75.1% in controls. There were twice as many ASA poor responders in DM than in controls (14.8% and 8.4%) based on systemic thromboxane reduction. Urinary 8-isoPGF2α excretion was greater in DM ASA poor responders than good responders (p<0.009). CONCLUSIONS This suggests that oxidative stress may maintain platelet function irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.
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Affiliation(s)
- Paul R J Ames
- Queen Mary University of London, William Harvey Research Institute, Centre for Sports and Exercise Medicine, Mile End Hospital, London, UK.
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Antolovic D, Rakow A, Contin P, Ulrich A, Rahbari NN, Büchler MW, Weitz J, Koch M. A randomised controlled pilot trial to evaluate and optimize the use of anti-platelet agents in the perioperative management in patients undergoing general and abdominal surgery--the APAP trial (ISRCTN45810007). Langenbecks Arch Surg 2011; 397:297-306. [PMID: 22048442 DOI: 10.1007/s00423-011-0867-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2011] [Accepted: 10/14/2011] [Indexed: 12/23/2022]
Abstract
PURPOSE Surgeons are increasingly confronted by patients on long-term low-dose acetylsalicylic acid (ASA). However, owing to a lack of evidence-based data, a widely accepted consensus on the perioperative management of these patients in the setting of non-cardiac surgery has not yet been reached. Primary objective was to evaluate the safety of continuous versus discontinuous use of ASA in the perioperative period in elective general or abdominal surgery. METHODS Fifty-two patients undergoing elective cholecystectomy, inguinal hernia repair or colonic/colorectal surgery were recruited to this pilot study. According to cardiological evaluation, non-high-risk patients who were on long-term treatment with low-dose ASA were eligible for inclusion. Patients were allocated randomly to continuous use of ASA or discontinuation of ASA intake for 5 days before until 5 days after surgery. The primary outcome was the incidence of major haemorrhagic and thromboembolic complications within 30 days after surgery. RESULTS A total of 26 patients were allocated to each study group. One patient (3.8%) in the ASA continuation group required re-operation due to post-operative haemorrhage. In neither study group, further bleeding complications occurred. No clinically apparent thromboembolic events were reported in the ASA continuation and the ASA discontinuation group. Furthermore, there were no significant differences between both study groups in the secondary endpoints. CONCLUSIONS Perioperative intake of ASA does not seem to influence the incidence of severe bleeding in non-high-risk patients undergoing elective general or abdominal surgery. Further, adequately powered trials are required to confirm the findings of this study.
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Affiliation(s)
- D Antolovic
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
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