Influence of polypharmacy on patients with heart failure with preserved ejection fraction: a retrospective analysis on adverse outcomes in the TOPCAT trial

Abstract

Background: Polypharmacy is common in heart failure (HF), whereas its effect on adverse outcomes in patients with HF with preserved ejection fraction (HFpEF) is unclear.

Aim: To evaluate the prevalence, prognostic impacts, and predictors of polypharmacy in HFpEF patients.

Design and setting: A retrospective analysis performed on patients in the Americas region (including the US, Canada, Argentina, and Brazil) with symptomatic HF and a left ventricular ejection fraction ≥45% in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial, an international, randomised, double-blind, placebo-controlled study conducted during 2006-2013 in six countries.

Method: Patients were categorised into four groups: controls (<5 medications), polypharmacy (5-9 medications), hyperpolypharmacy, (10-14 medications), and super hyperpolypharmacy (≥15 medications). The outcomes and predictors in all groups were assessed.

Results: Of 1761 participants, the median age was 72 years; 37.5% were polypharmacy, 35.9% were hyperpolypharmacy, and 19.6% were super hyperpolypharmacy, leaving 7.0% having a low medication burden. In multivariable regression models, three experimental groups with a high medication burden were all associated with a reduction in all-cause death, but increased risks of HF hospitalisation and all-cause hospitalisation. Furthermore, several comorbidities (dyslipidemia, thyroid diseases, diabetes mellitus, and chronic obstructive pulmonary disease), a history of angina pectoris, diastolic blood pressure <80 mmHg, and worse heart function (the New York Heart Association functional classification level III and IV) at baseline were independently associated with a high medication burden among patients with HFpEF.

Conclusion: A high prevalence of high medication burden at baseline was reported in patients with HFpEF. The high medication burden might increase the risk of hospital readmission, but not the mortality.

Trial registration: ClinicalTrials.gov NCT00094302.

Keywords: heart failure; hospitalisation; medication burden; outcome; patient readmission; polypharmacy.

© The Authors.

Figures

Figure 1.

The distribution of total medication burden at baseline in patients with heart failure with preserved ejection fraction.

Figure 2.

Medication usage characteristics in different medication burden status. ACEI = angiotensin-converting enzyme inhibitor. ARB = angiotensin receptor blocker. CCB = calcium channel blocker. CV = cardiovascular.

Figure 3.

Cumulative incidence curves. A) primary composite outcome; B) all-cause death; C) all-cause hospitalisation according to total medication burden at baseline. CIF = cumulative incidence function.