Low-dose rivaroxaban plus aspirin in patients with polypharmacy and multimorbidity: an analysis from the COMPASS trial.

BACKGROUND In patients with coronary or peripheral arterial disease, adding low dose rivaroxaban to aspirin reduces cardiovascular events and mortality. Polypharmacy and multimorbidity are frequent in such patients. AIMS To analyze whether the benefits and risks of rivaroxaban plus aspirin varies in patients with comorbidities and receiving multiple drugs. METHODS AND RESULTS We describe ischemic events (cardiovascular death, stroke, or myocardial infarction) and major bleeding in participants from the randomised, double-blind COMPASS study by number of cardiovascular medications and concomitant medical conditions. We compared event rates and hazard ratios (HR) for rivaroxaban plus aspirin versus aspirin alone by the number of medications and concomitant conditions, and tested for interaction between polypharmacy or multimorbidity and the antithrombotic regimen.The risk of ischemic events was higher in patients with more concomitant drugs (HR 1.7, 95%CI 1.5-2.1 for >4 vs 0-2) and with more comorbidities (HR 2.3, 1.8-2.1 for >3 vs 0-1). Multimorbidity, but not polypharmacy, was associated with a higher risk of major bleeding. The relative efficacy, safety, and net clinical benefit of rivaroxaban were not affected by the number of drugs or comorbidities. Patients taking more concomitant medications derived the largest absolute reduction in the net clinical outcome with added rivaroxaban (1.1% vs 0.4% reduction with >4 vs 0-2 cardiovascular drugs, NNT 91 vs 250). CONCLUSION Adding low-dose rivaroxaban to aspirin resulted in benefits irrespective of the number of concomitant drugs or comorbidities. Multiple comorbidities and/or polypharmacy should not dissuade the addition of rivaroxaban to aspirin in otherwise eligible patients.