Impact of COVID-19 in patients with heart failure with mildly reduced or preserved ejection fraction enrolled in the DELIVER trial

Ankeet S. Bhatt, Mikhail N. Kosiborod, Brian L. Claggett, Zi Michael Miao, Muthiah Vaduganathan, Carolyn S.P. Lam, Adrian F. Hernandez, Felipe A. Martinez, Silvio E. Inzucchi, Sanjiv J. Shah, Rudolf A. de Boer, Pardeep S. Jhund, Akshay S. Desai, James C. Fang, Yaling Han, Josep Comin-Colet, Jarosław Drożdż, Orly Vardeny, Bela Merkely, Daniel LindholmMagnus Peterson, Anna Maria Langkilde, John J.V. McMurray, Scott D. Solomon*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
6 Downloads (Pure)

Abstract

Aim: 

COVID-19 may affect clinical risk in patients with heart failure. DELIVER began before and was conducted during the COVID-19 pandemic. This study aimed to evaluate the association between COVID-19 and clinical outcomes among DELIVER participants. 

Methods and results: 

Participants with chronic heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) were randomized to dapagliflozin or placebo across 350 sites in 20 countries. COVID-19 was investigator-reported and the contribution of COVID-19 to death was centrally adjudicated. We assessed (i) the incidence of COVID-19, (ii) event rates before/during the pandemic, and (iii) risks of death after COVID-19 diagnosis compared to risks of death in participants without COVID-19. Further, we performed a sensitivity analysis assessing treatment effects of dapagliflozin vs. placebo censored at pandemic onset. Of 6263 participants, 589 (9.4%) developed COVID-19, of whom 307 (52%) required/prolonged hospitalization. A total of 155 deaths (15% of all deaths) were adjudicated as definitely/possibly COVID-19-related. COVID-19 cases and deaths did not differ by randomized assignment. Death rate in the 12 months following diagnosis was 56.1 (95% confidence interval [CI] 48.0–65.6) versus 6.4 (95% CI 6.0–6.8)/100 participant-years among trial participants with versus without COVID-19 (adjusted hazard ratio [aHR] 8.60, 95% CI 7.18–10.30). Risk was highest 0–3 months following diagnosis (153.5, 95% CI 130.3–180.8) and remained elevated at 3–6 months (12.6, 95% CI 6.6–24.3/100 participant-years). After excluding investigator-reported fatal COVID-19 events, all-cause death rates in the 12 months following diagnosis among COVID-19 survivors (n = 458) remained higher (aHR 2.46, 95% CI 1.83–3.33) than rates for all trial participants from randomization, with censoring of participants who developed COVID-19 at the time of diagnosis. Dapagliflozin reduced cardiovascular death/worsening HF events when censoring participants at COVID-19 diagnosis (HR 0.81, 95% CI 0.72–0.91) and pandemic onset (HR 0.72, 95% CI 0.58–0.89). There were no diabetic ketoacidosis or major hypoglycaemic events within 30 days of COVID-19. 

Conclusion: 

DELIVER is one of the most extensive experiences with COVID-19 of any cardiovascular trial, with >75% of follow-up time occurring during the pandemic. COVID-19 was common, with >50% of cases leading to hospitalization or death. Treatment benefits of dapagliflozin persisted when censoring at COVID-19 diagnosis and pandemic onset. Patients surviving COVID-19 had a high early residual risk. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03619213.

Original languageEnglish
Pages (from-to)2177-2188
Number of pages12
JournalEuropean Journal of Heart Failure
Volume25
Issue number12
Early online date28 Sept 2023
DOIs
Publication statusPublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

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