Outcomes
The primary efficacy outcome was defined as a composite of the occurrence of ischemic stroke (IS), transient ischemic attack (TIA), systemic embolism (SE), and cardiovascular/unexplained death. The primary safety outcome referred to the occurrence of major bleeding (MB) which was defined as BARC >2. The secondary safety outcome was the incidence of clinically relevant bleeding events, including MB and CRNMB. The combined hazard outcome (i.e., the net clinical benefit), was defined as the composite of the primary efficacy and primary safety outcomes. If a patient experienced more than one event(s) during follow-up, only the first event of a kind was considered. All the procedure-related events (bleeding due to vascular access and pericardial effusion, stroke/SE, or death ≤7 days within implantation), were not analyzed. Adverse events were adjudicated by a clinical event committee of two independent physicians, and, in case of disagreement, a third referee participated in the discussion.