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

Abstract

Introduction: COVID-19 may affect clinical risk in patients with heart failure. DELIVER began before and was conducted during the COVID-19 pandemic. Objective: We evaluated the association between COVID-19 and outcomes among DELIVER participants. Methods: Participants with chronic 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 (1) incidence of COVID-19, (2) event rates before/during the pandemic, and (3) risks of death after diagnosis compared to death in participants without COVID-19. Further, we performed a sensitivity analysis assessing treatment effects censored at pandemic onset. Results: Of 6263 participants, 589 (9.4%) developed COVID-19, of whom 307 (52%) required/prolonged hospitalization. 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% CI:48.0 to 65.6) vs. 6.4 (95% CI:6.0–6.8)/100-participant-years among trial participants with versus without COVID-19 (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 to 3.33) than all trial participants from randomization, with censoring of participants who developed COVID-19 at the time of diagnosis. Dapagliflozin reduced the CV 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 DKA or major hypoglycemic 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 event had a high early residual risk.

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Identifiers

DOI

https://doi.org/10.1002/ejhf.3043

Repository URI

https://eprints.gla.ac.uk/307595/