Wang Xiaowen, Vardeny Orly, Claggett Brian, Vaduganathan Muthiah, Hegde Sheila M, Skali Hicham, Pabon Maria A, Foà Alberto, Chatur Safia, Kosztin Annamaria, O'Meara Eileen, Rouleau Jean, Redfield Margaret, Lam Carolyn S P, Zile Michael, Packer Milton, Shah Amil M, Cikes Maja, Gori Mauro, Merkely Bela, Pfeffer Marc A, McMurray John J V, Solomon Scott D
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Minneapolis VA Center for Care Delivery and Outcomes Research University of Minnesota, Minneapolis, MN, USA.
Eur J Heart Fail. 2025 Jan;27(1):96-106. doi: 10.1002/ejhf.3535. Epub 2024 Dec 15.
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.
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.
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.
在PARAGON-HF试验中，评估沙库巴曲缬沙坦相对于缬沙坦在各年龄组中的临床结局、超声心动图特征以及疗效和安全性。
共有4796名年龄≥50岁的慢性心力衰竭（HF）患者且左心室射血分数（LVEF）≥45%被分为三个年龄组：<65岁（n = 825）、65 - 74岁（n = 1772）和≥75岁（n = 2199）。在一个核心影像实验室以标准化方式分析了1097例患者的超声心动图。主要复合结局为总的HF住院和心血管（CV）死亡。老年患者更有可能经历主要复合结局（与<65岁的患者相比，≥75岁患者的调整率比[aRR]：1.39，95%置信区间[CI] 1.21 - 1.61）、总的HF住院（aRR 1.27，95% CI 1.09 - 1.49）以及CV死亡（调整风险比[aHR] 2.04，95% CI 1.44 - 2.87）。在总体人群或LVEF≤57%的人群中，与缬沙坦相比，年龄并未改变沙库巴曲缬沙坦对主要复合终点的影响（p = 0.79）。与接受缬沙坦的患者相比，随机接受沙库巴曲缬沙坦的老年人更有可能发生低血压（p = 0.026）。老年患者的左心室腔尺寸较小、LVEF较高，并且更有可能出现舒张功能异常指标。
射血分数保留的老年HF患者比年轻患者有更高的事件发生率，总体不良事件更多，并且在接受沙库巴曲缬沙坦治疗时低血压更多；然而，沙库巴曲缬沙坦的治疗益处仍保留在老年患者中。
