Aspirin for Primary Prevention of Cardiovascular Disease in Diabetes: a Review of the Evidence
Purpose of Review
People with diabetes are at a higher risk of atherosclerotic cardiovascular disease (ASCVD) compared with those without diabetes. Though aspirin has been shown to have an overall net clinical benefit when used for secondary prevention of ASCVD in people with and without diabetes, the evidence for primary prevention, especially in those with diabetes, remains inconsistent. In this article, we review the latest studies examining the risks and benefits of aspirin use for primary prevention of ASCVD in adults with diabetes, discuss key aspects in assessing the risk-benefit ratio of aspirin use for primary prevention of ASCVD, and summarize current guidelines from professional societies on aspirin use for primary prevention in adults with diabetes.
In the general population, past studies have shown no difference in the beneficial effect of aspirin for primary cardiovascular disease prevention by diabetes status. However, several randomized controlled studies and meta-analyses in adults with diabetes have shown lack of net clinical benefit of aspirin use for primary prevention of ASCVD. The recent ASCEND trial documented cardiovascular benefit of aspirin for primary prevention in adults with diabetes but suggested that the increased risk of bleeding may outweigh the cardiovascular benefit.
The decision to initiate aspirin for primary prevention of ASCVD must be considered carefully on an individual basis to balance the cardiovascular benefit and bleeding risk in all patients, especially those with diabetes. A multifactorial approach that focuses on managing ASCVD risk factors such as hypertension, dyslipidemia, dysglycemia, and smoking is recommended in all patients. More research is needed to identify subgroups of people with diabetes who are more likely to benefit from aspirin use for primary prevention of ASCVD and develop better antithrombotic strategies that shift the risk-benefit balance toward an overall net clinical benefit.
KeywordsPrimary cardiovascular prevention Diabetes Aspirin Atherosclerotic cardiovascular disease
The Saudi Government Scholarship from King Saud University, Riyadh, Saudi Arabia provided fellowship training support to Dr. Al-Sofiani. Dr. Kalyani had funding provided by the National Institutes of Health/NIDDK (R03 DK109163).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 2.Sobel BE. Effects of glycemic control and other determinants on vascular disease in type 2 diabetes. Am J Med. 2002;113(Suppl 6A):22S.Google Scholar
- 15.Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early Treatment Diabetic Retinopathy Study report 14. ETDRS Investigators. JAMA. 1992;268(10):1292–300.Google Scholar
- 17.Saito Y, Okada S, Ogawa H, et al. Low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus: 10-year follow-up of a randomized controlled trial. Circulation. 2017;135(7):659–70. https://doi.org/10.1161/CIRCULATIONAHA.116.025760.CrossRefPubMedGoogle Scholar
- 18.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:a1840. https://doi.org/10.1136/bmj.a1840.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.•• Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60. https://doi.org/10.1016/S0140-6736(09)60503-1. Findings from this study showed that aspirin decreased the risk of vascular events by 12% in both the general population and in those with diabetes with no significant interaction by diabetes status. CrossRefGoogle Scholar
- 20.•• Al-Sofiani ME, Yanek LR, Faraday N, et al. Diabetes and platelet response to low-dose aspirin. J Clin Endocrinol Metab. 2018;103(12):4599–608. https://doi.org/10.1210/jc.2018-01254. A comprehensive examination of the in vivo and in vitro platelet activation and response to aspirin by diabetes status was performed in this study. CrossRefPubMedGoogle Scholar
- 26.Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Medical Research Council’s General Practice Research Framework. Lancet. 1998;351(9098):233–241Google Scholar
- 31.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. https://doi.org/10.1001/jama.2014.15690.CrossRefPubMedGoogle Scholar
- 32.•• ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379(16):1529–39. https://doi.org/10.1056/NEJMoa1804988. A recent trial that showed cardiovascular benefit of aspirin for primary prevention in people with diabetes but also suggested that the increased risk of bleeding may outweigh the cardiovascular benefit. CrossRefGoogle Scholar
- 33.Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018;392(10152):1036–46.CrossRefGoogle Scholar
- 36.Pignone M, Alberts MJ, Colwell JA, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation. 2010;121(24):2694–701. https://doi.org/10.1161/CIR.0b013e3181e3b133.CrossRefPubMedGoogle Scholar
- 42.Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):49. https://doi.org/10.1161/01.cir.0000437741.48606.98.CrossRefGoogle Scholar
- 47.Fox CS, Golden SH, Anderson C, et al. Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation. 2015;132(8):691–718. https://doi.org/10.1161/CIR.0000000000000230.CrossRefPubMedGoogle Scholar
- 48.Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Circulation. 2019:CIR0000000000000678. https://doi.org/10.1161/CIR.0000000000000678.
- 50.Bibbins-Domingo K, U S Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164(12):836–45. https://doi.org/10.7326/M16-0577.CrossRefPubMedGoogle Scholar
- 51.Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V RW, et al. ESC Scientific Document Group. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019;31. pii: ehz486. https://doi.org/10.1093/eurheartj/ehz486.
- 54.Zhang Z, Zhai Z, Yang Y, et al. Diabetes mellitus is associated with increased bleeding in pulmonary embolism receiving conventional anticoagulant therapy: findings from a “real-world” study. J Thromb Thrombolysis. 2017;43(4):540–9. https://doi.org/10.1007/s11239-017-1473-5.CrossRefPubMedGoogle Scholar
- 60.Capodanno D, Patel A, Dharmashankar K, et al. Pharmacodynamic effects of different aspirin dosing regimens in type 2 diabetes mellitus patients with coronary artery disease. Circ Cardiovasc Interv. 2011;4(2):180–7. https://doi.org/10.1161/CIRCINTERVENTIONS.110.960187.CrossRefPubMedGoogle Scholar