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

Abstract 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.