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Background: Guidelines for dabigatran in patients with atrial fibrillation (AF) recommend dose reduction in patients with impaired renal function and concomitant use of strong P-gp inhibitors. However, there are limited data regarding the safety and efficacy of concomitant use of dabigatran and p-gp inhibitors. We evaluated risk of major bleeding and stroke in patients with AF taking low (75 mg) or standard (150 mg) dose dabigatran with concomitant use of strong or moderate p-gp inhibitors and no history or renal disease.Methods: We identified Medicare beneficiaries age 66 and older with new AF diagnoses during 2011-2013 who received dabigatran within 90 days of AF diagnosis and had concurrent use of a P-gp inhibitor (droneradarone, amiodarone, ketoconazole, quinidine, verapamil, and clarithromycin). We excluded patients with existing renal disease, based on ICD-9-CM codes. We also excluded patients with recent hip surgery or recent embolism, to ensure that the purpose of dabigatran was long term stroke prevention. Of the 7,077 patients meeting inclusion criteria, 1,125 (16%) received dabigatran 75 mg; the remaining received 150 mg. We matched each patient taking low dose dabigatran to a single patient taking standard dose using an optimal propensity matching algorithm. Proportional hazards regression further controlled for patient attributes that may confound the relationship between dose and likelihood of stroke or bleeding. Matching and modeling steps were repeated 1000 times using bootstrapping. We then calculated the mean (and 95% confidence intervals) risk-adjusted stroke and bleeding rates per person-year.Results: There was a significant reduction in bleeding risk with use of low dose dabigatran, compared to standard dose, with an absolute reduction in bleeding risk of 23 per 1000 patient-years (95% CI, 1 to 45 per 1000 patient years). In contrast, the risk of stroke did not differ significantly among patients taking low or standard dose dabigatran (2 more strokes per 1000 patient-years with low dose dabigatran; 95% CI, -7 to 10).Conclusions: Use of low dose dabigatran in patients taking a P-gp inhibitor may result in fewer bleeding events compared to standard dose, without compromising the protective effect against ischemic stroke.