Polypharmacy is increasingly common among patients with heart failure (HF), including among those with mildly reduced (HFmrEF) and those with preserved ejection fraction (HFpEF) due to their high burden of comorbidities. Dapagliflozin effectively and safely reduces worsening HF or cardiovascular death in patients across a broad range of medication burden, according to a post hoc analysis of the DELIVER trial published June 21 in JACC: Heart Failure.

Alexander Peikert, MD, et al., examined the efficacy and safety of adding dapagliflozin across three categories of medication use at baseline: 1) nonpolypharmacy, <five medications; 2) polypharmacy, five to nine medications; 2) hyperpolypharmacy, ≥10 medications. Medications included vitamins and supplements.

Of the 6,263 participants in the DELIVER study, 3,795 patients (60.6%) were categorized as polypharmacy and 1,886 patients (30.1%) as hyperpolypharmacy. The mean number of medications was 8.4, and most of the medications in the polypharmacy and hyperpolypharmacy groups were noncardiovascular.

Results showed a strong association between the numbers of medications and a higher comorbidity burden and with increased rates of the primary outcome of worsening HF including unplanned HF hospitalization or cardiovascular death.

When comparing the benefit by polypharmacy status, dapagliflozin, vs. placebo, provided a similar reduction in the risk of the primary outcome: hazard ratio (HR) 0.88 for nonpolypharmacy, HR 0.88 for polypharmacy and HR 0.73 for hyperpolypharmacy (p for interaction=0.30). Dapagliflozin also provided a consistent benefit across the spectrum of total medication use (p for interaction=0.06).

The authors note that while the number of adverse events increased with the number of medications, no difference was seen with dapagliflozin regardless of polypharmacy status, nor was there any difference in treatment discontinuation. An improvement in health-related quality of life was also observed with dapagliflozin.

While noting that the results are exploratory and the small sample size, the authors write, “These findings further support the use of dapagliflozin as a safe and effective treatment option for patients with HFmrEF or HFpEF, even among those already on multiple medications.”

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Heart Failure, Polypharmacy

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