The COMPASS Trial: Net Clinical Benefit of Low-Dose Rivaroxaban Plus Aspirin as Compared With Aspirin in Patients...

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• The COMPASS trial demonstrated that rivaroxaban 2.5 mg twice daily plus aspirin (ASA) reduced cardiovascular events but increased major bleeding compared to ASA monotherapy.
• Net clinical benefit (NCB) analysis is crucial for evaluating the overall impact of treatments, integrating both efficacy and safety outcomes.

Purpose of the Study:

• To assess the net clinical benefit (NCB) of adding rivaroxaban 2.5 mg twice daily to aspirin in patients with chronic vascular disease.
• To specifically evaluate NCB in high-risk subgroups within the COMPASS study cohort.

Main Methods:

• A prespecified analysis of the COMPASS trial's intention-to-treat population was conducted.
• The predefined NCB outcome included cardiovascular death, stroke, myocardial infarction, fatal bleeding, or symptomatic bleeding into a critical organ.

Main Results:

• Rivaroxaban plus aspirin showed a lower incidence of NCB adverse outcomes compared to aspirin alone (HR, 0.80; P=0.0005), with benefits increasing over time.
• The primary drivers of NCB reduction were decreased rates of stroke and cardiovascular death.
• Bleeding events, while slightly increased, constituted a smaller proportion of NCB outcomes, and greater absolute risk reduction was observed in high-risk subgroups.

Conclusions:

• Combining rivaroxaban 2.5 mg twice daily with aspirin reduces NCB events by preventing major efficacy events like stroke and cardiovascular death.
• Severe bleeding events were less frequent and had a lower clinical impact, making the overall NCB favorable.
• The net clinical benefit was particularly pronounced in high-risk patients, including those with polyvascular disease, impaired renal function, heart failure, or diabetes.