Polypharmacy, as the use of five or more drugs, has commonly been associated with the elderly and multiple co-morbidities and related to impairment of clinical state and adverse outcomes, in general population. Limited data are available on the relationship between polypharmacy and adverse outcomes in atrial fibrillation (AF). We describe the prevalence of polypharmacy and AF, and its association with major adverse events, such as stroke and cardiovascular (CV) death.

For this study, we analysed all AFFIRM Trial patients with complete pharmacological data. Polypharmacy was recorded in 40 % of 4056 AF patients. The crude incidence of CV death was 3.45 % patient-years among patients with polypharmacy, vs 1.65 % patient-years without polypharmacy. Kaplan–Meier analysis showed that patients with polypharmacy had a higher cumulative incidence of CV death (p < 0.001). Cox regression analysis demonstrated that female gender (p = 0.038), diabetes mellitus (p = 0.029), previous myocardial infarction (MI) (p = 0.004), prior stroke (p = 0.011) and polypharmacy (p = 0.029) were independently associated with CV death. Polypharmacy was associated with an adjusted relative risk of 1.30 (95 % CI 1.03–1.64) for CV death. A linear increase in the number of drugs was significantly associated with CV death. No significant association was found with stroke occurrence.

Polypharmacy is highly prevalent in AF patients and associated with a worse clinical outcome, conferring 30 % excess relative risk for CV death. Thus, polypharmacy may be a health status marker. Strategies to reduce inappropriate prescription and polypharmacy should be tested in prospective longitudinal studies of AF patients.