Bleeding Risk During Use of Non-vitamin K Antagonist Oral Anticoagulants with Telmisartan versus Olmesartan in Patients with Non-Valvular Atrial Fibrillation

초록

Background: Telmisartan, a P-glycoprotein (P-gp) inhibitor, can reduce the metabolism of direct oral anticoagulants (DOACs), potentially increasing the risk of bleeding compared to other antihypertensive drugs that do not inhibit P-gp. Although the bleeding risk may vary when DOACs are used concurrently with P-gp inhibitors, clinical evidence directly comparing the clinical consequences of such drug interactions remains limited. Objectives: To compare the composite of intracranial hemorrhage and gastrointestinal bleeding risk in patients treated with DOACs in combination with olmesartan, which has low P-gp inhibitory activity, versus telmisartan, which has high P-gp inhibitory activity. Methods: We conducted a nationwide, population-based, retrospective, cohort study using Korean nationwide claims data (January 2016 to September 2023). Concomitant use of olmesartan or telmisartan at the time of DOAC initiation in patients with atrial fibrillation was identified. To minimize potential bias from an imbalance in observed covariate distribution between each treatment group, we used an inverse probability of treatment weighting approach. The primary outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding. The secondary outcomes included individual outcomes of the primary outcome, ischemic stroke, and all-cause mortality. We estimated the incidence rates, hazard ratios (HR) and 95% confidence intervals (CIs) using the Cox proportional hazards model. Results: Among 345,181 DOACs-treated patients with atrial fibrillation, 19,915 and 27,946 patients concomitantly used an olmesartan or telmisartan, respectively. After inverse probability of treatment weighting, 20,009.64 and 27,851.36 patients were selected. The incidence rates of primary outcome were in 6.69 per 1,000 person-years taking DOACs plus olmesartan and 9.13 per 1,000 person-years taking DOACs plus telmisartan, respectively (HR [95% CI] 0.74 [0.61–0.90]). The concomitant use of olmesartan was associated with significantly lower gastrointestinal bleeding (HR [95% CI] 0.67 [0.53–0.86]), but not with intracranial hemorrhage (HR [95% CI] 0.94 [0.65–1.36]), ischemic stroke (HR [95% CI] 1.06 [0.88–1.28]), and all-cause mortality (HR [95% CI] 1.03 [0.91–1.17]) in patients treated DOACs. Conclusions: Concurrent olmesartan was associated with decreased adverse bleeding risks in patients receiving DOACs compared to concurrent telmisartan.