Bad news for enthusiasts of left atrial appendage closure from #AHA25. CLOSURE-AF is not yet published, but reports from New Orleans indicate inferiority compared with best medical care (the trial was designed for non-inferiority, making this the most unexpected and unfavorable scenario). In 888 patients with atrial fibrillation considered at high risk for stroke and bleeding, a composite endpoint of stroke, systemic embolism, cardiovascular or unexplained death, and major bleeding occurred in 16.83% of patients who underwent left atrial appendage closure and 13.27% of those receiving best medical care (whose exact definition remains unclear — we’ll hopefully find out once the paper is available). These appear to be patients in whom the appendage is perhaps closed somewhat lightly — the rationale often being “so they won’t need lifelong anticoagulation.” Well, lifelong benefit remains to be seen, but after a median follow-up of 3 years, the risk of events was 28% higher with appendage closure, with a 95% confidence interval for the hazard ratio indicating a potential 1 to 62% increase in risk. In short, the results are not definitely encouraging, and much remains to be understood. Which events increased? Likely ischemic ones. And further — was it appropriate for the trial to combine ischemic and bleeding events, along with cardiovascular death, into a single non-inferiority endpoint? Probably not, yet the findings have disrupted expectations and made the discussion quite compelling nonetheless. Finally, could the expected long-term reduction in events (beyond 3 years, potentially lifelong) eventually offset the initial, possibly procedural and hemorrhagic, risks — shifting the balance back in favor of closure for patients with longer life expectancy and prolonged exposure to anticoagulation? Hard to say without full data. And in any case, this is only one trial; at least three others are ongoing in high bleeding-risk populations (STROKECLOSE, CLEARANCE, and LAA-KIDNEY). Let’s also recall that somewhat more favorable data have been seen in anticoagulation-eligible populations, but at this stage it seems appropriate to pause and reflect. If you’d like to reflect with us, join the @escardio webinar on Monday, where I’ll also be participating — it feels perfectly timed. esc365.escardio.org/event/20…