Polypharmacy in atrial fibrillation: An analysis of prospective outcomes using the Clinical Practice Research Datalink (CPRD)

Abstract

Objectives: Observational studies of polypharmacy and the risk of death or ischaemic stroke in individuals with atrial fibrillation (AF) have produced inconsistent findings. The reason for this variation may be due to differences in study designs and populations. By using propensity score matching, the aim of this study was to determine whether polypharmacy (5-9 prescribed medicines) and hyper-polypharmacy (=10 prescribed medicines) in the three months following AF diagnosis, are associated with an increased risk of death or ischaemic stroke, compared to non-polypharmacy (1-4 prescribed medicines).

Design: Prospective cohort study

Setting: Clinical Practice Research Datalink (CPRD) GOLD (June 2006 to April 2019)

Participants: 33,984 individuals with atrial fibrillation

Main outcome measures: Hazard ratios (HR) and 95% confidence intervals (CI) for the risk of death and ischaemic stroke. Logistic regression and propensity score matching (PSM) (1:1) were implemented in this study. Logistic models were adjusted for age, gender, eleven diagnosed conditions, obesity, alcohol consumption, smoking and wealth. In the PSM models, cases and controls with near identical health profiles were selected from the study pool.

Results: 47.9% (n=16,271) of the participants had polypharmacy, 30.4% (n= 10,355) had hyper-polypharmacy, while 21.7% (n=7, 358) had non-polypharmacy. PSM showed that polypharmacy was significantly associated with an increased risk of death during follow-up (HR 1.32; 95% CI: 1.19-1.47), but not ischaemic stroke (HR 0.84; 95% CI: 0.69-1.02). The risk of death during follow-up was accentuated in the hyper polypharmacy group (HR 1.89; 95% CI: 1.65-2.16); however, no significant association was found between hyper-polypharmacy and ischaemic stroke (HR 1.19; 95% CI: 0.91-1.57).

Conclusion: Polypharmacy and hyper-polypharmacy were significantly associated with an increased risk of death during follow-up, but not ischaemic stroke, in individuals with AF. The effect of comorbidity and other confounding factors was minimized by using propensity score matching in this large dataset. Further research conducted at drug class or individual drug level, could identify which medications, or combinations of medications, within polypharmacy and hyper-polypharmacy regimens are associated with an increased risk of death in AF. Identifying these medications could help to inform prescribing decisions and deprescribing practices in AF, and hence this study provides baseline data for future research. Furthermore, this research may develop our understanding regarding the lack of association between polypharmacy, hyper-polypharmacy, and ischemic stroke in AF.