Impact of Frailty on the Benefits of Dual Pathway Inhibition for the Secondary Prevention of Cardiovascular Events in the COMPASS Randomized Trial

Background Individuals with frailty are at higher risk of adverse cardiovascular outcomes and bleeding. The objective of this study was to determine whether the effects of rivaroxaban 2.5mg twice daily in addition to low-dose aspirin are similar among frail compared with non-frail patients with chronic atherosclerotic vascular disease. Methods In the COMPASS trial (ClinicalTrials.gov number NCT01776424), patients with chronic atherosclerotic vascular disease were randomized to receive aspirin 100mg daily, aspirin 100mg daily and rivaroxaban 2.5mg twice daily or rivaroxaban 5mg twice daily. In this post hoc analysis, frailty was evaluated by constructing a cumulative deficit index from 37 diseases, signs, and symptoms. The frailty index for each participant was calculated as the proportion of the 37 deficits exhibited, with values >0.2 considered frail. The primary outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Hazard ratios (HR) and 95% confidence intervals (CI) are reported. Results Frailty was present in 13% of the trial population. In non-frail individuals, adding rivaroxaban 2.5mg twice daily to aspirin reduced the primary outcome (HR, 95% CI: 0.69, 0.59-0.80) and mortality (0.75, 0.63-0.90) but increased major bleeding (1.87, 1.51-2.31); however, its effects on the primary outcome (1.06, 0.79-1.42), mortality (1.08, 0.80-1.46) and major bleeding (1.10, 0.71-1.70) were not evident among participants with frailty (respective interaction p-values 0.011, 0.049 and 0.032). Conclusions In adults with chronic atherosclerotic vascular disease, the benefit of adding rivaroxaban 2.5mg twice daily to aspirin was not evident in patients with frailty.