Polypharmacy and adverse events in atrial fibrillation: Main cause or reflection of multimorbidity?

Background: Previous evidence indicated that atrial fibrillation (AF) patients with polypharmacy presented increased probability of adverse events. We investigated the prevalence of polypharmacy, risk factors for polypharmacy, and the impact of polypharmacy in clinical outcomes in a 'real-world' cohort of AF patients starting vitamin K antagonists (VKAs). Methods: Prospective study including AF outpatients starting VKA therapy from July, 2016 to June, 2018. At inclusion, all concomitant drugs were carefully collected and recorded. Polypharmacy was defined as the intake of >= 5 concomitant drugs. During 2-years of follow-up, ischemic strokes/transient ischemic attacks (TIAs), fatal/ nonfatal myocardial infarctions (MIs), bleeding events, venous thromboembolisms, and all-cause deaths were recorded. Results: 1050 patients (51.5 % females, median age 77 [69-83] years) were included, and the prevalence of polypharmacy was 32.9 % (345). Female sex (OR 1.5; 95 % CI 1.11-2.03), hypertension (OR 2.53; 95 % CI 1.51-4.22), diabetes (OR 3.11; 95 % CI 2.31-4.17), vascular disease (OR 3.08; 95 % CI 2.19-4.33), heart failure (OR 1.86; 95 % CI 1.35-2.58) and dyslipidemia (OR 2.61; 95 % CI 1.9-3.58) were independently associated to the polypharmacy. Patients with polypharmacy showed significantly higher incidence of major bleeding, net clinical outcomes (composite of major bleeding, ischemic stroke/TIA, and mortality), MACE (composite of ischemic stroke/TIA, MI, and cardiovascular death), and composite thrombotic/thromboembolic events; being an independent risk factor for major bleeding (HR 1.77, 95 % CI 1.07-2.92), and composite thrombotic/ thromboembolic events (HR 1.55, 95 % CI 1.05-2.31). Conclusion: In this "real world" AF cohort, polypharmacy was highly prevalent and conditioned worse prognosis due to its association with bleeding and thromboembolic events.