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,Pardeep S Jhund,Anna Maria Langkilde,John J.V Mcmurray,Nathaniel M Hawkins,Marc S Sabatine,Piotr Ponikowski,Subodh Verma,Béla Merkely,Akshay S Desai,Rudolf A De Boer,Mark C Petrie,Mikail N Kosiborod,Lars Køber,Silvio E Inzucchi,Mikaela Sjöstrand,Masafumi Kitakaze,Olof Bengtsson,Daniel Lindholm,Scott D Solomon,Morten Schou,Jarosław Drożdż ,Felipe A Martínez

doi:10.1002/ejhf.2083

Abstract

AimsChronic 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 resultsWe 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].ConclusionsIn 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.

Highlights

Chronic obstructive pulmonary disease (COPD) has a higher prevalence in patients with heart failure (HF) than in the general population.[1,2,3] While this most likely reflects the common aetiological role of smoking in each condition, inflammation and oxidative stress have been postulated to play a role.[1,2,3] COPD is important in HF for two principal reasons
We examined whether the effects of dapagliflozin in DAPA-HF were modified by COPD status
Participants with COPD had a higher risk of the primary outcome

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) has a higher prevalence in patients with heart failure (HF) than in the general population.[1,2,3] While this most likely reflects the common aetiological role of smoking in each condition, inflammation and oxidative stress have been postulated to play a role.[1,2,3] COPD is important in HF for two principal reasons. Still indicated and generally well tolerated in most patients with COPD, even in high-risk settings, new evidence shows that beta-blockers can increase the risk of respiratory hospitalization in patients with more severe COPD.[8,9] It is advised that hydralazine and isosorbide dinitrate are avoided in patients with COPD as this combination may lead to worsening gas exchange and hypoxaemia.[7] hypokalaemia induced by beta-agonists, glucocorticoids and xanthine derivatives may make digoxin use more hazardous in patients with COPD, compared to those without and increase risk of arrhythmias.[7,10,11]

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