Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Meta-Analysis

Acetylsalicylic Acid (Aspirin) for Primary Prevention of Cardiovascular Events in Patients with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Author(s): Shuangbo Liu, Janine Eckstein, Anna Lam and Asim N. Cheema*

Volume 21, Issue 2, 2023

Published on: 27 February, 2023

Page: [111 - 119] Pages: 9

DOI: 10.2174/1570161121666230131120544

Price: $65

Abstract

Background: Evidence regarding using acetylsalicylic acid (aspirin) for the prevention of cardiovascular (CV) events in patients with diabetes mellitus (DM) is inconsistent. Therefore, we performed a meta-analysis.

Methods: A literature search was performed (January 1990 to February 2022) and publications meeting the inclusion criteria were reviewed, and a meta-analysis was performed using RevMan software. The primary outcome was a composite of CV death, non-fatal myocardial infarction (MI) and stroke. Secondary outcomes included all-cause mortality, individual components of the primary outcome and major bleeding.

Results: The study cohort comprised 33525 diabetic patients from 9 randomized controlled trials. The primary outcome was significantly lower for aspirin vs. placebo (7.9 vs. 8.6, RR (risk ratio) 0.92, 95% CI (confidence interval) 0.86-0.99). All-cause mortality (10 vs. 10.3%, RR 0.97, 95% CI 0.90-1.03), CV death (4.4 vs. 4.7%, RR 0.93, 95% CI 0.83-1.04), non-fatal MI (4.6 vs. 4.8% RR 0.97, 95% CI 0.83- 1.15) and stroke (3.2 vs. 3.5%, RR 0.89, 95% CI 0.75-1.06) were similar between the two treatment groups. Major bleeding was significantly higher for aspirin compared with placebo (3.4 vs. 2.8%, RR 1.18, 95% CI 1.01-1.39).

Conclusion: Aspirin use in patients with DM reduces the composite endpoint of CV death, non-fatal MI and stroke compared with a placebo. However, routine use of aspirin for primary prevention among diabetic patients cannot be advised due to the increased risk of major bleeding. These findings suggest careful risk assessment of individual patients.

Keywords: Acetylsalicylic acid, diabetes, primary prevention, cardiovascular (CV) events, non-fatal myocardial infarction (MI), stroke.

Graphical Abstract
[1]
Rawshani A, Rawshani A, Franzén S, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med 2017; 376(15): 1407-18.
[http://dx.doi.org/10.1056/NEJMoa1608664] [PMID: 28402770]
[2]
Rawshani A, Rawshani A, Gudbjörnsdottir S. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med 2017; 377(3): 300-1.
[http://dx.doi.org/10.1056/NEJMc1706292] [PMID: 28723317]
[3]
Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339(4): 229-34.
[http://dx.doi.org/10.1056/NEJM199807233390404] [PMID: 9673301]
[4]
Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: Factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008; 337(oct16 2): a1840.
[http://dx.doi.org/10.1136/bmj.a1840] [PMID: 18927173]
[5]
Kassoff A, Buzney SM, McMeel JW, et al. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early treatment diabetic retinopathy study report 14. JAMA 1992; 268(10): 1292-300.
[http://dx.doi.org/10.1001/jama.1992.03490100090033] [PMID: 1507375]
[6]
Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: Results of the Primary Prevention Project (PPP) trial. Diabetes Care 2003; 26(12): 3264-72.
[http://dx.doi.org/10.2337/diacare.26.12.3264] [PMID: 14633812]
[7]
Saito Y, Okada S, Ogawa H, et al. Low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes: 10-year follow-up of a randomized controlled trial. Circulation 2017; 135(7): 659-70.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.025760] [PMID: 27881565]
[8]
Bowman L, Mafham M, Wallendszus K, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018; 379(16): 1529-39.
[http://dx.doi.org/10.1056/NEJMoa1804988] [PMID: 30146931]
[9]
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(3): 316-27.
[http://dx.doi.org/10.1111/dme.13133] [PMID: 27086572]
[10]
Seidu S, Kunutsor SK, Sesso HD, et al. 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(1): 70.
[http://dx.doi.org/10.1186/s12933-019-0875-4] [PMID: 31159806]
[11]
Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre randomised placebo-controlled trial. Lancet 2004; 364(9435): 685-96.
[http://dx.doi.org/10.1016/S0140-6736(04)16895-5] [PMID: 15325833]
[12]
Khan SU, Ul Abideen Asad Z, Khan MU, et al. Aspirin for primary prevention of cardiovascular outcomes in diabetes mellitus: An updated systematic review and meta-analysis. Eur J Prev Cardiol 2020; 27(19): 2034-41.
[http://dx.doi.org/10.1177/2047487319825510] [PMID: 30700151]
[13]
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.
[http://dx.doi.org/10.1016/j.diabres.2016.07.012] [PMID: 27500549]
[14]
Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005; 352(13): 1293-304.
[http://dx.doi.org/10.1056/NEJMoa050613] [PMID: 15753114]
[15]
Higgins JPT, Lasserson T, Chandler J, Tovey D, Churchill R. Methodological expectations of Cochrane intervention reviews (MECIR). London: Cochrane 2016.
[16]
Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4(1): 1.
[http://dx.doi.org/10.1186/2046-4053-4-1] [PMID: 25554246]
[17]
Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21(11): 1539-58.
[http://dx.doi.org/10.1002/sim.1186] [PMID: 12111919]
[18]
CADTH. Grey matters: A practical tool for searching health-related grey literature. Ottawa: 2018. Available from: https://www.cadth.ca/resources/finding-evidence
[19]
Fortuni F, Crimi G, Gritti V, Mirizzi AM, Leonardi S, Ferrari GMD. Primum non nocere : An updated meta-analysis on aspirin use in primary prevention of cardiovascular disease in patients with diabetes. Eur J Prev Cardiol 2019; 26(15): 1677-9.
[http://dx.doi.org/10.1177/2047487319826439] [PMID: 30744399]
[20]
Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343(oct18 2): d5928.
[http://dx.doi.org/10.1136/bmj.d5928] [PMID: 22008217]
[21]
Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: A randomized clinical trial. JAMA 2014; 312(23): 2510-20.
[http://dx.doi.org/10.1001/jama.2014.15690] [PMID: 25401325]
[22]
Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension:Principal results of the hypertension optimal treatment (HOT) randomised trial. Lancet 1998; 351(9118): 1755-62.
[http://dx.doi.org/10.1016/S0140-6736(98)04311-6] [PMID: 9635947]
[23]
McNeil JJ, Nelson MR, Woods RL, et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 2018; 379(16): 1519-28.
[http://dx.doi.org/10.1056/NEJMoa1803955] [PMID: 30221595]
[24]
Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: Testing and clinical relevance. Circulation 2007; 115(10): 1285-95.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.652859] [PMID: 17353456]
[25]
Gimbrone MA Jr, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 2016; 118(4): 620-36.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306301] [PMID: 26892962]
[26]
Kim J, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathophysiological mechanisms. Circulation 2006; 113(15): 1888-904.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.563213] [PMID: 16618833]
[27]
Ferreiro JL, Gómez-Hospital JA, Angiolillo DJ. Review article: Platelet abnormalities in diabetes mellitus. Diab Vasc Dis Res 2010; 7(4): 251-9.
[http://dx.doi.org/10.1177/1479164110383994] [PMID: 20921090]
[28]
Ferroni P, Basili S, Falco A, Davì G. Platelet activation in type 2 diabetes mellitus. J Thromb Haemost 2004; 2(8): 1282-91.
[http://dx.doi.org/10.1111/j.1538-7836.2004.00836.x] [PMID: 15304032]
[29]
Schneider DJ. Factors contributing to increased platelet reactivity in people with diabetes. Diabetes Care 2009; 32(4): 525-7.
[http://dx.doi.org/10.2337/dc08-1865] [PMID: 19336636]
[30]
Vaduganathan M, Alviar CL, Arikan ME, et al. Platelet reactivity and response to aspirin in subjects with the metabolic syndrome. Am Heart J 2008; 156(5): e1-7.
[http://dx.doi.org/10.1016/j.ahj.2008.08.002]
[31]
Galli M, Andreotti F, D’Amario D, et al. Aspirin in primary prevention of cardiovascular disease in the elderly. Eur Heart J Cardiovasc Pharmacother 2020; 6(5): 326-7.
[http://dx.doi.org/10.1093/ehjcvp/pvz046] [PMID: 31504373]
[32]
American Diabetes Association. A. 10. Cardiovascular disease and risk management: Standards of medical care in diabetes-2021. Diabetes Care 2021; 44 (Suppl. 1): S125-50.
[http://dx.doi.org/10.2337/dc21-S010] [PMID: 33298421]
[33]
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020; 41(2): 255-323.
[http://dx.doi.org/10.1093/eurheartj/ehz486] [PMID: 31497854]
[34]
Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: Executive summary: A report of the american college of cardiology/american heart association task force on clinical practice guidelines. J Am Coll Cardiol 2019; 74(10): 1376-414.
[http://dx.doi.org/10.1016/j.jacc.2019.03.009] [PMID: 30894319]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy