Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER

Jawad H Butt, Henri Lu, Toru Kondo, Erasmus Bachus, Rudolf A de Boer, Silvio E Inzucchi, Pardeep S Jhund, Mikhail N Kosiborod, Carolyn S P Lam, Felipe A Martinez, Muthiah Vaduganathan, Scott D Solomon, John J V McMurray*

*Corresponding author for this work
6 Citations (Scopus)

Abstract

AIM: Chronic obstructive pulmonary disease (COPD) is common in heart failure with a mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and is associated with worse outcomes. In a pre-specified analysis of DELIVER, we investigated the relationship between COPD status and outcomes, and the efficacy and safety of dapagliflozin, compared with placebo, according to COPD status.

METHODS AND RESULTS: Patients with severe pulmonary disease (including COPD) were excluded from the trial. The primary outcome was a composite of cardiovascular death or worsening heart failure. Of the 6261 patients with data on baseline COPD status, 694 (11.1%) had a known history of this condition. The risk of the primary endpoint was higher in patients with mild-to-moderate COPD compared with those without COPD (adjusted hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.08-1.51). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status (no COPD: HR 0.82 [95% CI 0.72-0.93]; COPD: HR 0.82 [95% CI 0.62-1.10]; p interaction  = 0.98). Consistent effects were observed for heart failure, cardiovascular, and all-cause hospitalization, and deaths, and composites of these. Dapagliflozin, as compared with placebo, improved the Kansas City Cardiomyopathy Questionnaire scores from baseline to 8 months to a similar extent in patients with and without mild-to-moderate COPD (p interaction  ≥ 0.63). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status.

CONCLUSIONS: Mild-to-moderate COPD is common in patients with HFmrEF/HFpEF and is associated with worse outcomes. The beneficial effects of dapagliflozin compared with placebo on clinical events and symptoms were consistent, regardless of COPD status.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03619213.

Original languageEnglish
JournalEuropean Journal of Heart Failure
Volume25
Issue number11
Pages (from-to)2078-2090
Number of pages13
ISSN1388-9842
DOIs
Publication statusPublished - Nov 2023

Keywords

  • Chronic obstructive pulmonary disease
  • Clinical trial
  • Dapagliflozin
  • Heart failure
  • Outcomes

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