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

Wang X, Vardeny O, Claggett B, Vaduganathan M, Hegde SM, Skali H, Pabon MA, Foà A, Chatur S, Kosztin A, O'Meara E, Rouleau J, Redfield M, Lam CSP, Zile M, Packer M, Shah AM, Cikes M, Gori M, Merkely B, Pfeffer MA, McMurray JJV, Solomon SD. 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.

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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.