Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction.
Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction.
复制标题
范式-HF中与痴呆相关的不良事件和其他心力衰竭的试验，射血分数降低。
DOI：
10.1002/ejhf.687
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发表时间：
2017-01
影响因子：
18.2
通讯作者：
PARADIGM-HF Investigators and Committees
中科院分区：
文献类型：
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作者：
Cannon JA;Shen L;Jhund PS;Kristensen SL;Køber L;Chen F;Gong J;Lefkowitz MP;Rouleau JL;Shi VC;Swedberg K;Zile MR;Solomon SD;Packer M;McMurray JJ;PARADIGM-HF Investigators and Committees
抑制neprilysin（一种降解钠素和其他血管活性肽的酶）对心力衰竭伴射血分数降低（HFrEF）是有益的，正如PARADIGM‐HF所显示的，该研究比较了血管紧张素受体- neprilysin抑制剂（ARNI）苏比利/缬沙坦与依那普利。由于neprilysin也是清除大脑中淀粉样蛋白β肽的多种酶之一，因此理论上存在关于苏比里尔/缬沙坦对认知的长期影响的担忧。因此，我们研究了PARADIGM - HF中与痴呆相关的不良反应（ae），并将这些发现放在最近进行的其他HFrEF试验的背景下。在PARADIGM‐HF研究中，有症状的HFrEF患者按1:1的比例随机服用苏比利/缬沙坦97/103 mg b.d或依那普利10 mg b.d。我们系统地检索AE报告，使用规范活动医学词典（MedDRA）编码，使用标准化MedDRA查询（SMQs），与痴呆相关的“广义”和“狭义”首选术语。在PARADIGM‐HF研究中，8399名年龄在18-96岁的患者被随机分组，随访时间中位数为2.25年（最长为4.3年）。狭窄的SMQ搜索确定了27例与痴呆相关的ae：依那普利15例（0.36%），苏比里尔/缬沙坦12例（0.29%）[风险比（HR） 0.73, 95%可信区间（CI） 0.33-1.59]。广泛检索分别鉴定出97例（2.30%）和104例（2.48%）ae （HR 1.01, 95% CI 0.75-1.37）。在PARADIGM - HF的两个治疗组中，痴呆相关不良事件的发生率与最近其他三个HFrEF试验相似。我们没有发现证据表明，与依那普利相比，苏比里尔/缬沙坦增加了与痴呆相关的ae，尽管可能需要更长的随访时间来检测这种信号，并且需要更灵敏的工具来检测较小程度的认知障碍。有必要进一步研究这个问题。
Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM‐HF which compared the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid‐β peptides from the brain, there is a theoretical concern about the long‐term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia‐related adverse effects (AEs) in PARADIGM‐HF and placed these findings in the context of other recently conducted HFrEF trials. In PARADIGM‐HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA Queries (SMQs) with ‘broad’ and ‘narrow’ preferred terms related to dementia. In PARADIGM‐HF, 8399 patients aged 18–96 years were randomized and followed for a median of 2.25 years (up to 4.3 years). The narrow SMQ search identified 27 dementia‐related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on sacubitril/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33–1.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95% CI 0.75–1.37), respectively. The rates of dementia‐related AEs in both treatment groups in PARADIGM‐HF were similar to those in three other recent trials in HFrEF. We found no evidence that sacubitril/valsartan, compared with enalapril, increased dementia‐related AEs, although longer follow‐up may be necessary to detect such a signal and more sensitive tools are needed to detect lesser degrees of cognitive impairment. Further studies to address this question are warranted.