Published in the NEJM, three letters raise important points about CHAMPION-AF: 1) The primary endpoint includes cardiovascular death (42% of events), which is a “dilutive” component that does not characterize either treatment arm and favors a finding of noninferiority. 2) Focusing on ischemic stroke reveals a hazard ratio of 1.61 (95% CI, 1.00–2.59), with no difference in hemorrhagic stroke. This is somewhat the opposite of what one would expect from percutaneous LAAC. 3) The number of events was so much lower than anticipated that, while maintaining the same noninferiority margin, the trial effectively allowed a doubling of events while still declaring noninferiority. 4) It is inappropriate to consider the risk of intracranial hemorrhage solely as a function of oral anticoagulant exposure, while ignoring predisposing structural conditions such as cerebral amyloid angiopathy. nejm.org/doi/full/10.1056/NE…