Department of Medicine, Washington University, St Louis, Missouri, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
JACC Heart Fail. 2022 Jul;10(7):449-456. doi: 10.1016/j.jchf.2022.04.013.
The LIFE (LCZ696 In Hospitalized Advanced Heart FailurE) trial, which evaluated sacubitril/valsartan in patients with advanced heart failure (HF) with reduced ejection fraction and recent New York Heart Association functional class IV symptomatology, did not require tolerance to a renin angiotensin system antagonist before initiating sacubitril/valsartan, thus affording an opportunity to study the tolerability of sacubitril/valsartan in advanced HF with reduced ejection fraction.
The goal of this analysis of the LIFE trial is to characterize the tolerability of initiating sacubitril/valsartan in patients with chronic advanced HF with reduced ejection fraction.
In the LIFE trial, 445 subjects with advanced HF entered an unblinded run-in period of 3-7 days with sacubitril/valsartan 24/26 mg twice a day. The authors compared characteristics of subjects completing and failing run-in, performed multivariable analysis of clinical parameters associated with run-in failure, and developed a predictive model for short-term intolerance to sacubitril/valsartan.
Of 445 subjects entering run-in, 73 (18%) were intolerant of sacubitril/valsartan. Reasons for intolerance included systolic blood pressure <90 mm Hg (59%), symptoms of hypotension/dizziness with systolic blood pressure >90 mm Hg (19%), and renal dysfunction (creatinine >2.0 mg/dL) (12%). Multivariable predictors of intolerance included lower mean arterial pressure, lower serum chloride, presence of an implantable cardioverter-defibrillator and/or cardiac resynchronization device, moderate or greater mitral regurgitation, nonuse of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at the screening visit, and use of insulin at screening. Subjects with 4 or more predictors had a 48.9% probability of sacubitril/valsartan intolerance.
Intolerance to low doses of sacubitril/valsartan is common in patients with advanced chronic HF with reduced ejection fraction and may be predicted by the presence of certain risk factors. (EntrestoTM [LCZ696] in Advanced Heart Failure [LIFE Study] [HFN-LIFE] NCT02816736).
LIFE（LCZ696 在住院的晚期心力衰竭中的应用）试验评估了沙库巴曲缬沙坦在射血分数降低的晚期心力衰竭（HF）合并近期纽约心脏协会（NYHA）心功能 IV 级症状患者中的应用，在开始使用沙库巴曲缬沙坦之前，该试验不要求患者耐受肾素-血管紧张素系统拮抗剂，因此为研究射血分数降低的晚期心力衰竭患者应用沙库巴曲缬沙坦的耐受性提供了机会。
本项对 LIFE 试验的分析旨在描述射血分数降低的慢性晚期心力衰竭患者起始应用沙库巴曲缬沙坦的耐受性。
在 LIFE 试验中，445 例晚期 HF 患者入组无盲法洗脱期（3-7d），接受沙库巴曲缬沙坦 24/26mg，每日两次。研究者比较了完成和未完成洗脱期患者的特征，对与洗脱期失败相关的临床参数进行多变量分析，并建立了沙库巴曲缬沙坦短期不耐受的预测模型。
在 445 例入组患者中，有 73 例（18%）对沙库巴曲缬沙坦不耐受。不耐受的原因包括收缩压＜90mmHg（59%）、收缩压＞90mmHg 时出现低血压/头晕症状（19%）和肾功能不全（肌酐＞2.0mg/dL）（12%）。不耐受的多变量预测因素包括平均动脉压较低、血清氯较低、存在植入式心脏复律除颤器和/或心脏再同步治疗装置、中重度二尖瓣反流、在筛选就诊时未使用血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂、以及筛选时使用胰岛素。有 4 个或更多预测因素的患者应用沙库巴曲缬沙坦的概率为 48.9%。
射血分数降低的慢性晚期心力衰竭患者应用低剂量沙库巴曲缬沙坦时，通常会出现不耐受，某些危险因素可预测其不耐受。（EntrestoTM[LCZ696]在晚期心力衰竭[LIFE 研究][HFN-LIFE]NCT02816736）。
