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Dual Antiplatelet Therapy for Patients with Cardiovascular Disease


Am Fam Physician. 2019 Oct 15;100(8):463-464.

Clinical Question

Do patients with established cardiovascular disease who do not qualify for coronary stenting or those at increased risk of cardiovascular disease benefit from dual antiplatelet therapy (aspirin plus clopidogrel)?

Evidence-Based Answer

Patients with established cardiovascular disease or risk factors (e.g., ischemic cerebrovascular disease, peripheral arterial disease, high risk of atherothrombotic disease) should receive dual antiplatelet therapy with aspirin plus clopidogrel, which confers additional benefit over aspirin alone. (Strength of Recommendation [SOR]: A, based on meta-analyses of randomized controlled trials [RCTs].) Dual antiplatelet therapy decreases the risk of myocardial infarction (MI) and ischemic stroke (number needed to treat [NNT] = 77 and 43, respectively) with no change in mortality. It also increases the risks of major and minor bleeding (number needed to harm [NNH] = 111 and 30, respectively). Dual antiplatelet therapy has more benefit in patients who have established cardiovascular disease compared with those who have only risk factors (NNT to reduce composite of MI, stroke, and cardiovascular death = 100; NNT for all-cause mortality = 59). (SOR: B, based on a post hoc analysis of RCTs.)


A 2017 Cochrane meta-analysis found that dual antiplatelet therapy reduced the risk of MI and stroke and increased the risk of bleeding compared with aspirin alone, but it did not reduce mortality in patients with high risk of or known cardiovascular disease.1 Participants had known coronary artery disease, ischemic cerebrovascular disease, peripheral arterial disease, or a high risk of atherothrombotic disease (mean age: 60 to 65 years in most studies; 50% to 90% men). Patients were randomized to treatment with aspirin (70 to 325 mg daily) plus clopidogrel (75 mg daily in all but one RCT, which used 100 mg) vs. aspirin plus placebo for at least 30 days. Patients were followed for a median of 12 months. Dual antiplatelet therapy decreased fatal and nonfatal MI (relative risk

Address correspondence to Gary Kelsberg, MD, at Gary_Kelsberg@valleymed.org. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


show all references

1. Squizzato A, Bellesini M, Takeda A, et al. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events. Cochrane Database Syst Rev. 2017;(12):CD005158....

2. Bhatt DL, Fox KA, Hacke W, et al.; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706–1717.

3. Yusuf S, Zhao F, Mehta SR, et al.; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation [published corrections appear in N Engl J Med. 2001;345(20):1506 and N Engl J Med. 2001;345(23):1716]. N Engl J Med. 2001;345(7):494–502.

4. Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines [published correction appears in Chest. 2012;141(4):1129]. Chest. 2012;141(2 suppl):e637S–e668S.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (https://www.cebm.net).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to https://www.fpin.org or email: questions@fpin.org.

This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

A collection of FPIN's Clinical Inquiries published in AFP is available at https://www.aafp.org/afp/fpin.



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