Role of Combination Antiplatelet and Anticoagulation Therapy in Diabetes Mellitus and Cardiovascular Disease

Abstract

Background: Patients with established coronary artery disease (CAD) or peripheral artery disease (PAD) often have diabetes mellitus. These patients are at high risk of future vascular events. Methods: In a prespecified analysis of the COMPASS trial, we compared the effects of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg daily) versus placebo plus aspirin in patients with diabetes versus without diabetes in preventing major vascular events. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction (MI), or stroke. Secondary endpoints included all-cause mortality and all major vascular events (cardiovascular death, MI, stroke, or major adverse limb events including amputation). The primary safety endpoint was a modification of the International Society on Thrombosis and Haemostasis (ISTH) criteria for major bleeding. Results: There were 10,341 patients with diabetes and 17,054 without diabetes in the overall trial. There was a consistent and similar relative risk reduction for benefit of rivaroxaban plus aspirin (N=9,152) versus placebo plus aspirin (N=9,126) in patients both with (N=6,922) and without (N=11,356) diabetes for the primary efficacy endpoint (HR 0.74, p=0.002 and HR 0.77, p=0.005, respectively, p_interaction=0.77) and all-cause mortality (HR 0.81, p=0.05 and HR 0.84, p=0.09, respectively, p_interaction=0.82). However, though the absolute risk reductions appeared numerically larger in patients with versus without diabetes, both subgroups derived similar benefit (2.3% vs 1.4% for the primary efficacy endpoint at 3 years, Gail-Simon qualitative p_interactioninteraction=0.02; 2.7% vs 1.7% for major vascular events, p_interactioninteraction=0.001). Conclusions: In stable atherosclerosis, the combination of aspirin plus rivaroxaban 2.5 mg twice daily provided a similar relative degree of benefit on coronary, cerebrovascular, and peripheral endpoints in patients with and without diabetes. Given their higher baseline risk, the absolute benefits appeared larger in those with diabetes, including a three-fold greater reduction in all-cause mortality. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424