Mode of death in patients with heart failure and preserved ejection fraction: insights from PARAGON-HF

Desai, A. S. et al. (2021) Mode of death in patients with heart failure and preserved ejection fraction: insights from PARAGON-HF. Circulation: Heart Failure, 14(12), e008597. (doi: 10.1161/CIRCHEARTFAILURE.121.008597) (PMID:34807713)

Abstract

Background: Patients with heart failure (HF) and preserved left ventricular ejection fraction comprise a heterogeneous group including some with mildly reduced EF. We hypothesized that mode of death differs by EF in ambulatory patients with HF and preserved left ventricular ejection fraction. Methods: PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) compared clinical outcomes in 4796 patients with chronic HF and EF ≥45% randomly assigned to sacubitril/valsartan or valsartan. We examined the mode of death in relation to baseline EF in logistic regression models and the effect of randomized treatment on cause-specific death in Cox regression models. Nonlinear relationships with continuous EF were modelled using quadratic and cubic terms. Results: Of 691 deaths during the trial, 416 (60%) were ascribed to cardiovascular, 220 (32%) to noncardiovascular, and 55 (8%) to unknown causes. Of cardiovascular deaths, 154 (37%) were due to sudden death, 118 (28%) were due to HF, 35 (8%) to stroke, 27 (6%) to myocardial infarction, and 82 (20%) to other cardiovascular causes. Rates of all-cause, cardiovascular, and sudden death were higher in those with lower left ventricular ejection fraction (all P<0.001), while rates of non-cardiovascular death were greater in patients with higher EF. Sacubitril/valsartan did not reduce overall death, cardiovascular death, or sudden death compared with valsartan, irrespective of baseline EF (all P for interaction >0.30). Conclusions: Among patients with HF and preserved left ventricular ejection fraction enrolled in PARAGON-HF, the proportion of cardiovascular and sudden death were higher in those with lower left ventricular EF, and the proportion of noncardiovascular death rose with EF. Regardless of EF, sacubitril/valsartan did not reduce death from any cause compared with valsartan. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John and Cleland, Professor John
• Authors: Desai, A. S., Vaduganathan, M., Cleland, J. G., Claggett, B. L., Barkoudah, E., Finn, P., McCausland, F. R., Yilmaz, M. B., Lefkowitz, M., Shi, V., Pfeffer, M. A., McMurray, J. J.V., and Soloman, S. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Circulation: Heart Failure
• Publisher: American Heart Association
• ISSN: 1941-3289
• ISSN (Online): 1941-3297
• Published Online: 22 November 2021