Rivaroxaban With or Without Aspirin in Patients With Heart Failure and Chronic Coronary or Peripheral Artery Disease

Abstract

Background: Patients with chronic coronary artery disease or peripheral artery disease and history of heart failure (HF) are at high risk for major adverse cardiovascular events. We explored the effects of rivaroxaban with or without aspirin in these patients.

Methods: The COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized 27 395 participants with chronic coronary artery disease or peripheral artery disease to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg alone. Patients with New York Heart Association functional class III or IV HF or left ventricular ejection fraction (EF) <30% were excluded. The primary major adverse cardiovascular events outcome comprised cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome was major bleeding using modified International Society of Thrombosis and Haemostasis criteria. Investigators recorded a history of HF and EF at baseline, if available. We examined the effects of rivaroxaban on major adverse cardiovascular events and major bleeding in patients with or without a history of HF and an EF <40% or ≥40% at baseline.

Results: Of the 5902 participants (22%) with a history of HF, 4971 (84%) had EF recorded at baseline, and 12% had EF <40%. Rivaroxaban and aspirin had similar relative reduction in major adverse cardiovascular events compared with aspirin in participants with HF (5.5% versus 7.9%; hazard ratio [HR], 0.68; 95% CI, 0.53-0.86) and those without HF (3.8% versus 4.7%; HR, 0.79; 95% CI, 0.68-0.93; P for interaction 0.28) but larger absolute risk reduction in those with HF (HF absolute risk reduction 2.4%, number needed to treat=42; no HF absolute risk reduction 1.0%, number needed to treat=103). The primary major adverse cardiovascular events outcome was not statistically different between those with EF <40% (HR, 0.88; 95% CI, 0.55-1.42) and ≥40% (HR, 0.81; 95% CI, 0.67-0.98; P for interaction 0.36). The excess hazard for major bleeding was not different in participants with HF (2.5% versus 1.8%; HR, 1.36; 95% CI, 0.88-2.09) than in those without HF (3.3% versus 1.9%; HR, 1.79; 95% CI, 1.45-2.21; P for interaction 0.26). There were no significant differences in the primary outcomes with rivaroxaban alone.

Conclusions: In patients with chronic coronary artery disease or peripheral artery disease and a history of mild or moderate HF, combination rivaroxaban and aspirin compared with aspirin alone produces similar relative but larger absolute benefits than in those without HF.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Keywords: aspirin; cardiovascular diseases; coronary artery disease; heart failure; peripheral artery disease; randomized controlled trial; rivaroxaban.

Figures

Figure 1.

Kaplan–Meier cumulative hazard rates.A, Composite outcome of cardiovascular death, stroke, or myocardial infarction. B, Death from any cause. C, Major bleeding, by heart failure status at baseline and treatment with rivaroxaban plus aspirin or aspirin alone. Events were tabulated as time to first event. HF indicates heart failure.

Figure 2.

Clinical trial events in patients with HF and CAD or PAD treated with rivaroxaban with or without aspirin. Comparison of total event rates for primary end point, their components, and noncardiovascular death in COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure) and in patients in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) with HF, by left ventricular ejection fraction category. Multiple events could occur in a single patient. ACS indicates acute coronary syndrome; ASA, aspirin; ATLAS ACS-2, Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome; CAD, coronary artery disease; CV, cardiovascular; EF, ejection fraction; HF, heart failure; PAD, peripheral artery disease; and Riva, rivaroxaban.