Rhythm-Guided Pill-in-the-Pocket Anticoagulation Following Cryoballoon Ablation: A COMPARE-CRYO post-hoc analysis.

BACKGROUND: Current guidelines recommend lifelong oral anticoagulation (OAC) for atrial fibrillation (AF) patients based on stroke risk, regardless of AF burden. Post-AF ablation trials report lower than expected stroke rates, raising the question of whether OAC could be reserved for periods of AF recurrence: rhythm-guided pill-in-the-pocket strategy. OBJECTIVE: Characterise long-term AF burden post-ablation and modelled rhythm guided OAC. METHODS: Post-hoc analysis of the COMPARE-CRYO trial of paroxysmal AF patients undergoing first-time cryoablation with continuous ICM monitoring. AF episodes were independently adjudicated. Rhythm-guided OAC strategies were modelled in patients with CHA2DS2-VA ≥1, triggered by daily burden of ≥6 minutes, ≥1 hour, ≥5.5 hours, and ≥23.5 hours with different OAC window durations. RESULTS: Among 201 patients over a median follow-up of 3.3 years, median daily AF burden was 0% (IQR, 0-0.01%), with AF absent on 96.5% of days. Of 108 patients with recurrence, 40% maintained very low burden (<0.1%) and 36% had low burden (0.1-1%). Among 139 patients with CHA2DS2-VA ≥1 a restart-and-continue strategy triggered by AF ≥6 minutes resulted in OAC during 32% of follow-up. Pill-in-the-pocket strategies with fixed OAC windows (14 or 30 days) reduced OAC by 90.8-99.4%. The ≥1-hour threshold with 30-day OAC window provided the most favourable balance, covering 97.5% of time in AF whilst reducing OAC exposure by 90.8%. CONCLUSIONS: Most patients maintained a consistently low AF burden after cryoablation. Rhythm-guided anticoagulation could substantially reduce OAC, with the ≥1-hour threshold best balancing OAC reduction and time-in-AF coverage. These strategies require prospective evaluation of clinical outcomes.