Cardiovascular Outcomes According to Polypharmacy and Drug Adherence in Patients with Atrial Fibrillation on Long-Term Anticoagulation (from the RE-LY Trial).

Prevalence of atrial fibrillation (AF) increases with age, along with comorbidities and, thus, polypharmacy. Non-adherence is associated with polypharmacy. This study aimed to identify patients at risk for cardiovascular events according to their pharmacological treatment intensity and adherence. Patients (n = 18,113) with a mean age of 71.5 ± 8.7 years, at high cardiovascular risk were followed between December 2005 until December 2007 for a median time of 2 years. The association between polypharmacy and adherence and their impact on cardiovascular and bleeding events were explored. Adherence was defined as a study drug intake of ≥80%. Patients with more co-medications had a higher body mass index, higher prevalence of hypertension, coronary heart disease, heart failure, and diabetes mellitus (all p < 0.0001) compared to ≤4 or 5-8 co-medications, but no differences in history of stroke (p = 0.68) or transient ischemic attack (p = 0.065). Across all treatments, the adjusted hazard ratios (HRs) increased in patients with more co-medications (≥9 vs ≤4) for all-cause death (HR 1.30; 1.06-1.59), major bleeding (HR 1.65; 1.33-2.05), and all bleeding events (HR 1.44; 1.31-1.59). Yearly event rates were higher in non-adherent than adherent patients for stroke and systemic embolism (SSE) (3.14 vs 1.00), all-cause death (7.76 vs 2.66), major bleeding (6.21 vs 2.65), and all bleeding (28.71 vs 19.05; all p < 0.0001). After an event the patients were more likely to become non-adherent (adherence after SSE 30.3%, after major bleeding 33.4%, after all bleeding 66.7%; all p < 0.0001). The treatment effects were consistent to the overall group in the different polypharmacy groups. In conclusion, polypharmacy and non-adherence are risk indicators for increased adverse cardiovascular and bleeding events. Dabigatran is safe to use across the full spectrum of AF patients, independent of the number of co-medications and adherence. Patients with co-medications and comorbidities require special attention and encouragement to adhere to oral anticoagulation.