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 2.5 mg rivaroxaban twice daily in addition to low-dose aspirin are similar among frail compared with nonfrail patients with chronic atherosclerotic vascular disease.

Methods: In the COMPASS trial (NCT01776424), patients with chronic atherosclerotic vascular disease were randomised to receive 100 mg aspirin daily, 100 mg aspirin daily plus 2.5 mg rivaroxaban twice daily, or 5 mg rivaroxaban 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 to be frail. The primary outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Hazard ratios (HRs) and 95% confidence intervals (CIs) are reported.

Results: Frailty was present in 13% of the trial population. In nonfrail individuals, adding 2.5 mg rivaroxaban twice daily to aspirin reduced the primary outcome (HR 0.69, 95% CI 0.59-0.80) and mortality (HR 0.75, 95% CI 0.63-0.90), but increased major bleeding (HR 1.87, 95% CI 1.51-2.31); Among participants with frailty, its effects on the primary outcome (HR 1.06, 95% CI 0.79-1.42), mortality (HR 1.08, 0.80-1.46), and major bleeding (HR 1.10, 95% CI 0.71-1.70) were not evident (respective interaction P values 0.011, 0.049, and 0.032).

Conclusions: In adults with chronic atherosclerotic vascular disease, the benefit of adding 2.5 mg rivaroxaban twice daily to aspirin was not evident in patients with frailty.

Clinical trial registration: NCT01776424.