Comparative bleeding risk between angiotensin II receptor blockers with high versus low P-glycoprotein inhibitory activity in patients with atrial fibrillation receiving direct oral anticoagulants

Direct oral anticoagulants (DOACs) are frequently co-prescribed with angiotensin II receptor blockers (ARBs) in atrial fibrillation (AF). Because ARBs differ in P-glycoprotein (P-gp) inhibition, bleeding risk may vary. We compared major bleeding when DOACs were combined with telmisartan (high P-gp inhibition) versus olmesartan (low P-gp inhibition). We conducted a nationwide cohort study from 2016-2023 in Korea. We identified AF patients who started a DOAC with telmisartan or olmesartan. The primary outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding. Secondary outcomes included each component of the primary outcome and ischemic stroke. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Among DOAC-treated patients with AF, 27,851 and 20,010 patients were included in the telmisartan and olmesartan groups, respectively. The incidence rates of the primary outcome were 9.13 per 1000 person-years in the telmisartan group and 6.69 in the olmesartan group (HR 1.35, 95% CI 1.11-1.65). Concomitant use of telmisartan was associated with a higher risk of gastrointestinal bleeding (1.49, 1.17-1.89), but not with intracranial hemorrhage (1.06, 0.74-1.54) or ischemic stroke (0.94, 0.78-1.14). Among patients with AF using DOACs, concomitant use of ARBs with high P-gp inhibitory activity was associated with a significantly higher risk of major bleeding and gastrointestinal bleeding compared-ARBs with low P-gp inhibitory activity. These findings suggest that differences in P-gp inhibitory activity among ARBs may influence bleeding risk in clinical practice when co-administered with DOACs.