Antiplatelet therapy and risk of adverse cardiovascular events in peripheral artery disease

Abstract

Abstract Background Antiplatelet therapy has been shown to reduce adverse cardiovascular (CV) events in patients with PAD, but despite the well-established medication benefit, large-scale epidemiological data evaluating antiplatelet agent of choice with low bleeding risk and high antithrombotic effect is sparse. Purpose We explored Danish healthcare registers to examine guideline-recommended antiplatelet therapy and associated risk of adverse CV outcomes in patients with PAD. Methods All patients with a first-time diagnosis of PAD between January 1, 1997 and December 31, 2016 were identified. Patients alive six months after diagnosis were divided into four treatment groups: aspirin, clopidogrel, dual therapy (DAPT), and no antiplatelet therapy. Logistic regression models were used to estimate 1-year risk of myocardial infarction (MI), stroke, CV death, all-cause mortality, and gastrointestinal (GI) bleeding. Results We identified a total of 85,771 PAD patients [median age 70.6 (IQR 63–77 years), 52% male]. The results suggest that compared to no antiplatelet therapy, use of clopidogrel alone significantly decreased 1-year risk of incident MI, stroke, CV death and all-cause mortality with odds ratios 0.56 (CI 0.46–0.68), 0.69 (CI 0.59–0.81), 0.72 (CI 0.56–0.94), and 0.79 (CI 0.65–0.97) respectively. Likewise, aspirin monotherapy was associated with only a marginal reduction in 1-year risk of stroke by 11% and all-cause mortality by 7%. Odds ratios for GI bleeding were estimated to be 1.18 (CI 1.04–1.34), 1.34 (CI 0.94–1.91), and 1.54 (CI 1.05–2.26) for aspirin, clopidogrel, and DAPT groups, respectively. Conclusion In this nationwide study, clopidogrel is associated with significantly reduced risk of MI, stroke, CV death and all-cause mortality with low risk of bleeding and appears to support clopidogrel as antiplatelet agent of choice for CV risk reduction in patients with PAD. Funding Acknowledgement Type of funding sources: None.