Empagliflozin and risk of lower respiratory tract infection in heart failure with mildly reduced and preserved ejection fraction: An EMPEROR‐Preserved analysis

Abstract

AimsLower respiratory tract infections (LRTI) are common worldwide. Patients with heart failure and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) have a high risk of developing LRTI. Prior studies were able to show that sodium–glucose cotransporter 2 inhibitors may reduce the incidence of LRTI in patients with type 2 diabetes. The aim of this study was to evaluate patient characteristics and prognosis according to LRTI status and to assess the effect of empagliflozin on LRTI in 5988 patients with HFmrEF/HFpEF enrolled in the EMPEROR‐Preserved trial randomized to either empagliflozin or placebo over a median follow‐up of 26 months.Methods and resultsTime‐updated models were used to study the mortality risk after a LRTI. Cox regression was used to study the effect of empagliflozin on incident LRTI. Throughout the follow‐up, 699 of 5988 (11.7%) patients developed LRTI: these were older, were more frequently hospitalized within the previous year, had type 2 diabetes, chronic kidney disease, and had higher N‐terminal pro‐B‐type natriuretic peptide levels than patients without incident LRTI. Patients who developed LRTI had a 2.7‐fold higher risk of subsequent mortality compared to patients without LRTI. The incidence of LRTI was 5.2 (95% confidence interval [CI] 4.6–5.8) events per 100 person‐years in the empagliflozin group and 6.2 (95% CI 5.6–6.9) events per 100 person‐years in the placebo group (hazard ratio 0.83, 95% CI 0.71–0.96, p = 0.014). The total number of LRTI events was reduced in the empagliflozin group (incidence rate ratio 0.80, 95% CI 0.68–0.94, p = 0.008). No effect of empagliflozin was observed on COVID‐19 incidence.ConclusionIn EMPEROR‐Preserved, LRTI was frequent and associated with a poor prognosis. Empagliflozin was associated with a reduced risk of LRTI compared to placebo.