Division of Internal Medicine, Department of Medicine, University of Miami/Jackson Memorial Hospital, 1611 NW 12th Ave, Central Building 600D, Miami, FL, 33136, USA.
Division of Cardiovascular Disease, Jackson Memorial Hospital, 1801 NW 9th Ave, Suite #209, Miami, FL, 33136, USA.
Am J Cardiovasc Drugs. 2021 May;21(3):267-270. doi: 10.1007/s40256-020-00445-7. Epub 2020 Oct 16.
Sacubitril/valsartan is a new medication approved for the treatment of heart failure with reduced ejection fraction. While the drug failed to meet the primary endpoint in patients with heart failure with preserved ejection fraction in the PARAGON-HF trial, improvements were noted in several secondary endpoints. Valsartan is an angiotensin receptor blocker and sacubitril is a neprilysin inhibitor. Neprilysin is postulated to have a role in the degradation of beta-amyloid in the brain; therefore, sacubitril could theoretically increase beta-amyloid plaque deposition in the brain and potentially increase the risk of Alzheimer's disease. Although pre-clinical and clinical studies have shown promising safety results, those studies have been heavily criticized for short monitoring time and targeted populations. In accordance with the requirements of the US Food and drug Administration (FDA), the ongoing Prospective Evaluation of Cognitive Function in Heart Failure: Efficacy and Safety of Entresto compared to Valsartan on Cognitive Function in Patients with Chronic Heart Failure and Preserved Ejection Fraction (PERSPECTIVE; NCT02884206) multicenter, randomized, double-blinded trial is assessing the long-term neurocognitive effects and safety of sacubitril/valsartan, and results are expected in early 2022.
沙库巴曲缬沙坦是一种新的药物，被批准用于治疗射血分数降低的心力衰竭。尽管该药在 PARAGON-HF 试验中未能达到射血分数保留的心力衰竭患者的主要终点，但在几个次要终点上有改善。缬沙坦是一种血管紧张素受体阻滞剂，沙库巴曲是一种脑啡肽酶抑制剂。脑啡肽酶被认为在大脑中β-淀粉样蛋白的降解中起作用；因此，沙库巴曲理论上可能会增加大脑中的β-淀粉样蛋白斑块沉积，并可能增加阿尔茨海默病的风险。尽管临床前和临床研究显示出有希望的安全性结果，但这些研究因监测时间短和目标人群而受到广泛批评。根据美国食品和药物管理局 (FDA) 的要求，正在进行的前瞻性心力衰竭认知功能评估：Entresto 与缬沙坦对慢性心力衰竭和射血分数保留患者认知功能的疗效和安全性比较（PERSPECTIVE；NCT02884206）多中心、随机、双盲试验正在评估沙库巴曲缬沙坦的长期神经认知效应和安全性，预计结果将于 2022 年初公布。
