■提出了一种假设的担忧,即沙库巴曲/缬沙坦可能会导致认知障碍,因为脑啡肽是降解大脑中淀粉样β肽的几种酶之一,其中一些具有神经毒性,与阿尔茨海默型痴呆有关。为了解决这个问题,我们在一项预先设定的PARAGON-HF亚研究(血管紧张素受体Neprilysin抑制剂与血管紧张素受体阻滞剂在射血分数保留的心力衰竭中的全球结局的前瞻性比较)中,研究了沙库巴曲/缬沙坦对射血分数保留的心力衰竭患者认知功能的影响。
■在PARAGON-HF中,在接受简易精神状态检查的部分患者中进行了认知功能的系列评估(MMSE;评分范围,0-30,得分较低反映认知功能较差)。此子研究的预设主要分析是在96周时MMSE评分相对于基线的变化。其他事后分析包括认知下降(MMSE评分下降≥3分),认知障碍(MMSE评分<24),或痴呆相关不良事件的发生。
■在MMSE子研究中纳入的2895名患者中,测量了基线MMSE评分,1453例患者被分配到沙库巴曲/缬沙坦,1442例被分配到缬沙坦。他们的平均年龄是73岁,中位随访时间为32个月.沙库巴曲/缬沙坦组随机分组时的平均±SDMMSE评分为27.4±3.0,10%的患者MMSE评分<24;缬沙坦组的相应数字几乎相同。沙库必曲/缬沙坦组从基线到96周的平均变化为-0.05(SE,0.07);缬沙坦组的相应变化为-0.04(0.07)。在第96周,治疗之间的平均差异为-0.01(95%CI,-0.20至0.19;P=0.95)。MMSE下降≥3点的分析,降低至<24分,痴呆相关不良事件,这些组合在沙库巴曲/缬沙坦和缬沙坦之间没有差异。在接受载脂蛋白Eε4等位基因基因型测试的患者亚组中没有发现差异。
在PARAGON-HF中射血分数保留的心力衰竭患者的基线MMSE评分相对较低。认知变化,通过MMSE测量,在射血分数保留的心力衰竭患者中,沙库巴曲/缬沙坦治疗与缬沙坦治疗之间没有差异。
■URL:https://www。clinicaltrials.gov;唯一标识符:NCT01920711。
UNASSIGNED: A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction).
UNASSIGNED: In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0-30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSE score of ≥3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events.
UNASSIGNED: Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was -0.05 (SE, 0.07); the corresponding change in the valsartan group was -0.04 (0.07). The mean between-treatment difference at week 96 was -0.01 (95% CI, -0.20 to 0.19; P=0.95). Analyses of a ≥3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E ε4 allele genotype.
UNASSIGNED: Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction.
UNASSIGNED: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.