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

Pooja Dewan, Kieran F Docherty, Olof Bengtsson, Rudolf A de Boer, Akshay S Desai, Jaroslaw Drozdz, Nathaniel M Hawkins, Silvio E Inzucchi, Masafumi Kitakaze, Lars Køber, Mikail N Kosiborod, Anna Maria Langkilde, Daniel Lindholm, Felipe A Martinez, Béla Merkely, Mark C Petrie, Piotr Ponikowski, Marc S Sabatine, Morten Schou, Mikaela Sjöstrand, Scott D Solomon, Subodh Verma, Pardeep S Jhund, John J V McMurray, Pooja Dewan, Kieran F Docherty, Olof Bengtsson, Rudolf A de Boer, Akshay S Desai, Jaroslaw Drozdz, Nathaniel M Hawkins, Silvio E Inzucchi, Masafumi Kitakaze, Lars Køber, Mikail N Kosiborod, Anna Maria Langkilde, Daniel Lindholm, Felipe A Martinez, Béla Merkely, Mark C Petrie, Piotr Ponikowski, Marc S Sabatine, Morten Schou, Mikaela Sjöstrand, Scott D Solomon, Subodh Verma, Pardeep S Jhund, John J V McMurray

Abstract

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.

© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Figures

Figure 1
Figure 1
Efficacy of dapagliflozin in DAPA‐HF according to chronic obstructive pulmonary disease (COPD) status at baseline. HF, heart failure.
Figure 2
Figure 2
Risk of primary outcome and all‐cause mortality associated with major comorbidities.
Figure 3
Figure 3
(A) Individual Kansas City Cardiomyopathy Questionnaire (KCCQ) domain scores at baseline by chronic obstructive pulmonary disease (COPD) status. (B) Baseline KCCQ scores associated with major comorbidities.
Figure 4
Figure 4
Effect of randomized treatment on change in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores from baseline to 8 months according to chronic obstructive pulmonary disease (COPD) status.

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