Polypharmacy and health outcomes in atrial fibrillation: a systematic review and meta-analysis

Objective: To undertake a systematic review and meta-analysis examining the impact of polypharmacy on health outcomes in atrial fibrillation (AF). Data sources: PubMed and Embase databases were searched from inception until 31 July 2019. Studies including post hoc analyses of prospective randomised controlled trials or observational design that examined the impact of polypharmacy on clinically significant outcomes in AF including mortality, hospitalisations, stroke, bleeding, falls and quality of life were eligible for inclusion. Results: A total of six studies were identified from the systematic review, with three studies reporting on common outcomes and used for a meta-analysis. The total study population from the three studies was 33 602 and 37.2% were female. Moderate and severe polypharmacy, defined as 5-9 medicines and >9 medicines, was observed in 42.7% and 20.7% of patients respectively, and was associated with a significant increase in all-cause mortality (Hazard ratio [HR] 1.36, 95% CI 1.20 to 1.54, p<0.001; HR 1.84, 95% CI 1.40 to 2.41, p<0.001, respectively), major bleeding (HR 1.32, 95% CI 1.14 to 1.52, p<0.001; HR 1.68, 95% CI 1.35 to 2.09, p<0.001, respectively) and clinically relevant non-major bleeding (HR 1.12, 95% CI 1.03 to 1.22, p<0.01; HR 1.48, 95% CI 1.33 to 1.64, p<0.01, respectively). There was no statistically significant association between polypharmacy and stroke or systemic embolism or intracranial bleeding. Among other examined outcomes, polypharmacy was associated with cardiovascular death, hospitalisation, reduced quality of life and poorer physical function. Conclusions: Polypharmacy is highly prevalent in the AF population and is associated with numerous adverse outcomes. PROSPERO registration number: CRD42018105298.