Criticism

1. Exclusion of 2,320 participants after run-in period (due to failure to adhere/tolerate) raises possibility of selection bias and decreased generalizability.
2. Study terminated early due to efficacy of rivaroxaban + aspirin vs. aspirin alone. Thus, the study may overestimate the degree of benefit of rivaroxaban + aspirin and potentially underestimate the degree of increased bleeding with this therapy.
3. The lack of statistical significance of the observed trend towards improved mortality with combination rivaroxaban + aspirin may be due to underpowering for this outcome.