PROTECT-AF (LAA Closure with Watchman vs Warfarin in AF and Stroke) A long-term (45-month) follow-up analysis of device therapy with Watchman vs warfarin for LAA closure with respect to all-cause and CV mortality and hemorrhagic stroke in patients with nonvalvular atrial fibrillation and stroke risk factors Population and treatment: 800 patients followed up for a mean of 45 months, or an aggregate of 2621 patient-years, randomized to either the Watchman device or warfarin Primary end points: Efficacy: Stroke, systemic embolism, or CV or unexplained death Safety: A composite of serious pericardial effusion, major bleeding, procedure- related stroke, hemorrhagic stroke, and device embolization VY Reddy (Mount Sinai School of Medicine, New York, NY) Heart Rhythm Society (HRS) 2013 Scientific Sessions LAA=Left Atrial Appendage

PROTECT-AF: Results End pointsRR (95%CI) Primary efficacy end point: Stroke, systemic embolism, or CV or unexplained death 0.60 (0.41–1.05) All-cause mortality0.66 (0.45–0.98) Cardiovascular mortality0.40 (0.21–0.72) Hemorrhagic stroke0.15 (0.03–0.49) Primary safety end point: Serious pericardial effusion, major bleeding, procedure-related stroke, hemorrhagic stroke, and device embolization 1.17 (0.78–1.95) The new data confirm that the Watchman is noninferior and show for the first time that it is superior to warfarin for the composite primary efficacy end point of stroke, systemic embolism, or cardiovascular or unexplained death. LAA closure with the Watchman device is superior to warfarin with respect to all-cause and CV mortality and hemorrhagic stroke in patients with nonvalvular atrial fibrillation and stroke risk factors. The observed 40% drop in primary events were fairly consistent throughout most of the trial, but only with the latest long-term analysis reached statistical superiority. Rate ratios for primary efficacy and safety end points and secondary end points in PROTECT-AF, by intention to treat

PROTECT-AF: Commentary* *All comments from Long-term PROTECT-AF analysis: Watchman attains efficacy superiority over warfarin in AF ( "This is statistically nonsignificant for the first time. The reason is, even though there [was] a high number of [mostly procedure-related] events up front in the Watchman group, there [were] cumulative events in the warfarin group. So by the time we have the four-year analysis, the event rate is statistically similar. "The difference is that the confidence intervals have narrowed, meaning, as we have more data accumulated, we have become more and more confident that that 40% decrease is actually... a real end point, not just by chance. The amount of benefit hasn't really changed; what has changed is our certainty that the number is really true." - Dr Vivek Y Reddy