Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction According to Polypharmacy Status.

Scott D Solomon, John J V McMurray, Rudolf A de Boer, Carolyn S P Lam, Pardeep S Jhund, Zi Michael Miao, Ian J Kulac, Parag Goyal, Alexander Peikert, Orly Vardeny, Brian L Claggett, Felipe A Martinez, Muthiah Vaduganathan, Sanjiv J Shah, Mikhail N Kosiborod, Silvio E Inzucchi, Adrian F Hernandez, Anna Maria Langkilde, Magnus Petersson, Akshay S Desai

Journal: JACC. Heart failure 2023;11(10):1380-1393

PMID: 37294244

Free Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Patients with heart failure (HF) have a high burden of multimorbidity, often necessitating numerous medications. There may be clinical concern about introducing another medication, especially among individuals with polypharmacy.

OBJECTIVES

This study examined the efficacy and safety of addition of dapagliflozin according to the number of concomitant medications in HF with mildly reduced or preserved ejection fraction.

METHODS

In this post hoc analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, 6,263 participants with symptomatic HF with left ventricular ejection fraction >40% were randomized to dapagliflozin or placebo. Baseline medication use (including vitamins and supplements) was collected. Efficacy and safety outcomes were assessed by medication use categories ("nonpolypharmacy": <5 medications; "polypharmacy": 5 to 9 medications; and "hyperpolypharmacy": ≥10 medications) and continuously. The primary outcome was worsening HF or cardiovascular death.

RESULTS

Overall, 3,795 (60.6%) patients met polypharmacy and 1,886 (30.1%) met hyperpolypharmacy criteria. Higher numbers of medications were strongly associated with higher comorbidity burden and increased rates of the primary outcome. Compared with placebo, dapagliflozin similarly reduced the risk of the primary outcome irrespective of polypharmacy status (nonpolypharmacy HR: 0.88 [95% CI: 0.58-1.34]; polypharmacy HR: 0.88 [95% CI: 0.75-1.03]; hyperpolypharmacy HR: 0.73 [95% CI: 0.60-0.88]; P = 0.30). Similarly, benefits with dapagliflozin were consistent across the spectrum of total medication use (P = 0.06). Although adverse events increased with higher number of medications, they were not more frequent with dapagliflozin, regardless of polypharmacy status.

CONCLUSIONS

In the DELIVER trial, dapagliflozin safely reduced worsening HF or cardiovascular death across a broad range of baseline medication use, including among individuals with polypharmacy (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).

Address: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Division of Cardiology and Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.; Minneapolis VA Center for Care Delivery and Outcomes Research, University of Minnesota, Minneapolis, Minnesota, USA.; Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri, USA.; BHF Glasgow Cardiovascular Research Center, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland, United Kingdom.; National Heart Centre Singapore and Duke-National University of Singapore, Singapore; University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.; Yale School of Medicine, New Haven, Connecticut, USA.; Universidad Nacional de Córdoba, Córdoba, Argentina.; Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, the Netherlands.; Duke University Medical Center, Durham, North Carolina, USA.; Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R and D, AstraZeneca, Gothenburg, Sweden.; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: [email protected].

DOI: 10.1016/j.jchf.2023.05.014