Effect of sacubitril/valsartan in heart failure with preserved ejection fraction across the age spectrum in PARAGON-HF.

Wang, Vardeny, Claggett, Vaduganathan, Hegde, Skali, Pabon, Foà, Chatur, Kosztin, O'Meara, Rouleau, Redfield, Lam, Zile, Packer, Shah, Cikes, Gori, Merkely, Pfeffer, McMurray, Solomon. Effect of sacubitril/valsartan in heart failure with preserved ejection fraction across the age spectrum in PARAGON-HF. European journal of heart failure. 2025 Jan 1; 27(1):96-106, DOI: 10.1002/ejhf.3535.

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Abstract:

AIMS: To evaluate clinical outcomes, echocardiographic features, and the efficacy and safety of sacubitril/valsartan compared to valsartan across age groups in the PARAGON-HF trial. METHODS AND RESULTS: A total of 4796 participants = 50?years of age with chronic heart failure (HF) and left ventricular ejection fraction (LVEF)? = 45% were divided into three age groups: < 65?years (n? = 825), 65-74?years (n? = 1772), and? = 75?years (n? = 2199). Echocardiograms of 1097 patients were analysed in a standardized fashion at a core imaging laboratory. The primary composite outcome was total HF hospitalizations and cardiovascular (CV) death. Older patients were more likely to experience primary composite outcomes (compared to patients < 65?years, adjusted rate ratio [aRR] for = 75?years: 1.39, 95% confidence interval [CI] 1.21-1.61), total HF hospitalization (aRR 1.27, 95% CI 1.09-1.49), and CV death (adjusted hazard ratio [aHR] 2.04, 95% CI 1.44-2.87). Age did not modify the effect of sacubitril/valsartan compared to valsartan on primary composite endpoint (p? = 0.79) in the overall population or in those with LVEF = 57%. Older adults randomized to sacubitril/valsartan were more likely to develop hypotension compared to those receiving valsartan (p? = 0.026). Older patients had smaller left ventricular chamber sizes, higher LVEF, and were more likely to have abnormal measures of diastolic function. CONCLUSION: Older patients with HF with preserved ejection fraction had higher event rates than younger patients, more adverse events overall, and more hypotension when treated with sacubitril/valsartan; however, the treatment benefits of sacubitril/valsartan were retained in older patients.