Effects of dapagliflozin in heart failure with reduced ejection fraction and chronic obstructive pulmonary disease: an analysis of DAPA-HF

Eur J Heart Fail. 2021 Apr;23(4):632-643. doi: 10.1002/ejhf.2083. Epub 2021 Jan 18.


Aims: Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure (HF) with reduced ejection fraction (HFrEF), associated with worse outcomes and often suboptimal treatment because of under-prescription of beta-blockers. Consequently, additional effective therapies are especially relevant in patients with COPD. The aim of this study was to examine outcomes related to COPD in a post hoc analysis of the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial.

Methods and results: We examined whether the effects of dapagliflozin in DAPA-HF were modified by COPD status. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Overall, 585 (12.3%) of the 4744 patients randomized had a history of COPD. Patients with COPD were more likely to be older men with a history of smoking, worse renal function, and higher baseline N-terminal pro B-type natriuretic peptide, and less likely to be treated with a beta-blocker or mineralocorticoid receptor antagonist. The incidence of the primary outcome was higher in patients with COPD than in those without [18.9 (95% confidence interval 16.0-22.2) vs. 13.0 (12.1-14.0) per 100 person-years; hazard ratio (HR) for COPD vs. no COPD 1.44 (1.21-1.72); P < 0.001]. The effect of dapagliflozin, compared with placebo, on the primary outcome, was consistent in patients with [HR 0.67 (95% confidence interval 0.48-0.93)] and without COPD [0.76 (0.65-0.87); interaction P-value 0.47].

Conclusions: In DAPA-HF, one in eight patients with HFrEF had concomitant COPD. Participants with COPD had a higher risk of the primary outcome. The benefit of dapagliflozin on all pre-specified outcomes was consistent in patients with and without COPD.

Clinical trial registration: ClinicalTrials.gov ID NCT03036124.

Keywords: Chronic obstructive pulmonary disease; Dapagliflozin; Heart failure.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzhydryl Compounds
  • Glucosides / therapeutic use
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Humans
  • Male
  • Pulmonary Disease, Chronic Obstructive* / complications
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / epidemiology
  • Stroke Volume


  • Benzhydryl Compounds
  • Glucosides
  • dapagliflozin

Associated data

  • ClinicalTrials.gov/NCT03036124