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.