Duration of heart failure with preserved ejection fraction and outcomes with sacubitril/valsartan: insights from the PARAGON-HF trial

Ostrominski, J. W. et al. (2023) Duration of heart failure with preserved ejection fraction and outcomes with sacubitril/valsartan: insights from the PARAGON-HF trial. Journal of Cardiac Failure, 29(11), pp. 1494-1503. (doi: 10.1016/j.cardfail.2023.05.003) (PMID:37220823)

Abstract

Objective: In this post hoc analysis of the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, we evaluated clinical outcomes and responses to sacubitril/valsartan by duration of heart failure (HF) with left ventricular ejection fraction ≥ 45% at initial diagnosis. Methods and Results: The primary outcome was a composite of total hospitalizations due to HF and cardiovascular deaths, analyzed by using a semiparametric proportional rates method, stratified by geographic region. Among 4784 (99.7%) randomized participants in the PARAGON-HF trial for whom baseline HF duration was captured, 1359 (28%) had durations of HF of < 6 months, 1295 (27%) of 6 months–2 years, and 2130 (45%) of > 2 years. Longer HF duration was associated with higher comorbidity burdens, worse health status and lower rates of prior hospitalization due to HF. Over a median follow-up of 35 months, longer HF duration was associated with a higher risk of first and recurrent primary events (per 100 patient-years): < 6 months, 12.0 (95% CI, 10.4–14.0); 6 months–2 years, 12.2 (10.6–14.2); > 2 years, 15.8 (14.2–17.5). Relative treatment effects of sacubitril/valsartan vs valsartan were consistent, irrespective of baseline HF duration on the primary endpoint (Pinteraction = 0.112). Clinically meaningful (≥ 5 point) improvements in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Scores were also similarly observed, irrespective of HF duration; (Pinteraction = 0.112). Adverse events were similar between treatment arms across HF duration categories. Conclusions: In PARAGON-HF, longer HF duration was independently predictive of adverse HF outcomes. Treatment effects of sacubitril/valsartan were consistent, irrespective of baseline HF duration, suggesting that even ambulatory patients with longstanding HFpEF and predominantly mild symptoms stand to benefit from treatment optimization.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jhund, Professor Pardeep and McMurray, Professor John
• Authors: Ostrominski, J. W., Claggett, B. L., Packer, M., Pfeffer, M. A., Lam, C. S.P., Zile, M. R., Desai, A. S., Jhund, P. S., Lefkowitz, M., McMurray, J. J.V., Solomon, S. D., and Vaduganathan, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Cardiac Failure
• Publisher: Elsevier
• ISSN: 1071-9164
• ISSN (Online): 1532-8414
• Published Online: 21 May 2023