Effectiveness of empagliflozin in patients with heart failure and COPD: Results from EMPEROR-Preserved and EMPEROR-Reduced

Abstract Background Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive syndromes that share numerous risk factors and clinical symptoms. We sought to analyse the relationship between COPD status and outcomes in patients receiving empagliflozin or placebo in the EMPEROR-Preserved and EMPEROR-Reduced trials. Methods and results We analyzed data of 9,718 patients, including 1,238 (12.7%) with COPD. Compared to patients without COPD, patients with COPD were more likely to be in NYHA class III (19.4 vs. 28.4%), to be male (62.4 vs. 69.0%), to have higher body mass index (29.0±5.7 vs. 29.5±6.1 kg/m2), to be white, to be smoker or ex-smoker (47.1 vs. 71.9%), to be older (69.6±10.5 vs. 72.1±8.7y, all p<0.0001), to have a longer duration of HF (5.0 vs. 5.4y, p=0.04), to have higher haemoglobin and high-sensitivity troponin T values (both p<0.01), and a trend towards more advanced kidney dysfunction. Patients with COPD exhibited a higher adjusted risk of reaching the primary endpoint of first HF hospitalization or CV death compared to those without COPD (adjusted hazard ratio [HR] 1.52, 95% confidence interval [95% CI] 1.28-1.80, p<0.0001). The favorable impact of empagliflozin on the primary outcome remained consistent regardless of COPD status at baseline (no COPD: HR 0.76, 95% CI 0.68-0.84, COPD: HR 0.82, 95% CI 0.66-1.03, p for interaction 0.50, Figure). The effects on HF hospitalizations, cardiovascular and all-cause mortality were not affected by COPD status. The Kansas City Cardiomyopathy Questionnaire showed similar improvement in patients with or without COPD treated with empagliflozin. The distribution of adverse events was comparable between patients receiving empagliflozin and those on placebo, irrespective of COPD status at baseline. Conclusions COPD is frequently encountered in patients with HF and associated with worse outcomes. Among patients with COPD, treatment with empagliflozin is associated with consistent efficacy on outcomes and improvement in quality of life as in patients without COPD.