Heart Failure, Investigator-Reported Sleep Apnea and Dapagliflozin: A Patient-Level Pooled Meta-Analysis of DAPA-HF and DELIVER

JAWAD H. BUTT, KAROLA JERING, RUDOLF A. DE BOER, BRIAN L. CLAGGETT, AKSHAY S. DESAI, ADRIAN F. HERNANDEZ, SILVIO E. INZUCCHI, PARDEEP S. JHUND, L. A.R.S. KØBER, MIKHAIL N. KOSIBOROD, CAROLYN S.P. LAM, FELIPE A. MARTINEZ, PIOTR PONIKOWSKI, MARC S. SABATINE, SANJIV J. SHAH, MUTHIAH VADUGANATHAN, ANNA MARIA LANGKILDE, O. L.O.F. BENGTSSON, MAGNUS PETERSSON, MIKAELA SJÖSTRANDULRICA WILDERÄNG, SCOTT D. SOLOMON, JOHN J.V. MCMURRAY*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Sleep apnea is more common in patients with heart failure (HF) than in the general population, but little is known about its association with clinical outcomes in various HF phenotypes or how it might modify the effect of HF therapy. Objectives: To examine the prevalence of sleep apnea, its association with outcomes and the effects of dapagliflozin in patients with HF with and without sleep apnea in a pooled analysis of 2 trials comparing dapagliflozin to placebo in HFrEF (DAPA-HF trial) and HFmrEF/HFpEF (DELIVER trial). Methods: A history of sleep apnea was investigator-reported. The primary outcome was a composite of worsening HF or cardiovascular death. Results: The prevalence of sleep apnea was 5.7% and 7.8% in patients with HFrEF and HFmrEF/HFpEF, respectively. The primary outcome occurred at a rate of 16.0 in participants with sleep apnea compared to 10.6 per 100 person-years in those without (adjusted HR 1.29 [95%CI, 1.10–1.52]). Compared with placebo, dapagliflozin reduced the risk of the primary endpoint to the same extent in patients with (HR 0.78 [95% CI, 0.59–1.03]) and without sleep apnea (HR 0.79 [0.72–0.87]) [Pinteraction = 0.93]. The beneficial effects of dapagliflozin on other clinical outcomes and symptom burden, physical function, and quality of life were consistent in participants with and without sleep apnea. Conclusions: In DAPA-HF and DELIVER, the true prevalence of sleep apnea was likely underestimated. An investigator-reported history of sleep apnea was associated with higher rates of worsening HF events. The benefits of dapagliflozin on clinical outcomes were consistent in patients with and without sleep apnea. Clinical trial registration: Unique identifiers: NCT01920711 Condensed Abstract: In a pooled analysis of the DAPA-HF and DELIVER trials of more than 11,000 patients with heart failure (HF) across the range of ejection fractions, an investigator-reported history of sleep apnea was associated with higher rates of worsening HF events but not mortality. The beneficial effects of dapagliflozin on clinical outcomes were consistent in patients with and without sleep apnea. These findings provide further evidence for dapagliflozin as a new treatment option for patients with heart failure across the range of ejection fractions.

Original languageEnglish
Pages (from-to)436-448
Number of pages13
JournalJournal of Cardiac Failure
Volume30
Issue number3
Early online date15 Dec 2023
DOIs
Publication statusPublished - Mar 2024

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