Anticoagulation-associated bleeding in patients screened for asymptomatic atrial fibrillation vs. usual care – A post-hoc analysis from the LOOP study

Background Atrial fibrillation (AF) prevalence is rising, however data on the bleeding risks associated with detection of subclinical AF are needed. Objective To determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared to usual care. Methods This post-hoc study utilized LOOP trial data from 6004 elderly patients with stroke risks randomised to either ILR (n=1503) or usual care (n=4503). The mean follow-up time was 64.5 months, and none were lost to follow-up. The primary exposure was the initiation of oral anticoagulation, and the main outcome was the risk of major bleeding events following initiation of oral anticoagulants (OAC), determined by time-dependent cox regression. Secondly, we investigated antithrombotic prescription patterns and major bleeding events after antiplatelets treatment and in subgroups. Results OAC was initiated in 1019 participants with a mean age (yrs) at 78.8 (±4.67) in Control vs. 77.0 (±4.84) in ILR, p<0.0001. All cases of OAC discontinuation reached 202, and in AF-patients (n=910) alone paused 105 (72%) paticipants temporarily OAC and 40 (28%) ended OAC treatment completelety during follow-up. Major bleeding events totalled 221 (3.7%). Forty-seven major bleeding events followed an OAC initiation in 1019 participants (4.6%); 26 vs. 21 events in the control and ILR group respectively. The hazard ratio (HR) for major bleeding after OAC initiation compared to before was 2.08 (1.50-2.90) p<0.0001 overall; 2.81 (1.82-4.34) p<0.0001 for Control and 1.32 (0.78-2.23) p=0.31 for the ILR group (p=0.07 for interaction). Antiplatelet treatment resulted in an overall adjusted HR of 1.3 (0.96-1.75) p=0.09. For OAC-users aged ≥75 years in the ILR group, the rate of major bleeding was 1.73 (0.92-2.96) compared to 0.84 (0.36-1.66) for an age <75 years, and the rate of the corresponding Control subgroup aged ≥75 years was 2.20 (1.23-3.63) compared to 1.64 (0.82-2.93) for an age <75 years. Conclusion The individual risk of major bleeding increased two-fold after initiation of oral anticoagulation for all patients in this study. However, the patients screened for subclinical AF did not have a higher bleeding risk after initiation of anticoagulation compared to those in usual care.