Abstract

Introduction: Patients with comorbid heart failure (HF) and chronic kidney disease (CKD) face excess risks of mortality, but limited data are available examining specific modes of death across the spectrum of kidney function. Methods: We leveraged individual patient level data from 5 trials of HF with mildly reduced or preserved ejection (CHARM-Preserved, I Preserve, TOPCAT [Americas region], PARAGON-HF, and DELIVER). Causes of death (sudden, heart failure, other CV, and non-CV) were adjudicated by clinical events committees in each respective trial. Results: Among 17,947 patients across the 5 trials with available eGFR data, mean age was 71.6 ± 9.0 years, 51% were women, median NT-proBNP was 840 [25-75 th percentile 424, 1566] pg/ml. Overall, 2084 (12%) had eGFR ≥90 mL/min/1.73m 2 , 7977 (44%) had eGFR 60 - < 90, 4701 (26%) had eGFR 45-60, 3185 (18%) had eGFR <45. During a mean of 2.9 years of follow-up, 3,140 patients died. All-cause death rate was greater in the lower eGFR groups, driven by greater rates of HF and non-CV death. Rates of CV and non-CV death were 5.7/100 patient years (py) and 4.4/100py in patients with eGFR <45 and 2.7/100py and 1.3/100py in patients with eGFR >90 (Table and Figure). HF-related death rate was markedly greater in participants with eGFR <45 (2.0/100py) compared to patients with eGFR>90 (0.3/100py) Conclusions: Among nearly 18,000 patients across contemporary HFmrEF/HFpEF clinical trials, mortality was markedly higher at lower ranges of kidney function, driven mostly by higher non-CV death and HF-related death.