Effect of Neprilysin Inhibition on Left Ventricular Remodeling in Patients With Asymptomatic Left Ventricular Systolic Dysfunction Late After Myocardial Infarction.
Effect of Neprilysin Inhibition on Left Ventricular Remodeling in Patients With Asymptomatic Left Ventricular Systolic Dysfunction Late After Myocardial Infarction.
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DOI：
10.1161/circulationaha.121.054892
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发表时间：
2021-07-20
期刊：
影响因子：
37.8
通讯作者：
McMurray JJV
中科院分区：
文献类型：
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作者：
Docherty KF;Campbell RT;Brooksbank KJM;Dreisbach JG;Forsyth P;Godeseth RL;Hopkins T;Jackson AM;Lee MMY;McConnachie A;Roditi G;Squire IB;Stanley B;Welsh P;Jhund PS;Petrie MC;McMurray JJV
补充数字内容可在文本中找到。心肌梗死后左心室（LV）收缩功能障碍的患者发生心力衰竭的风险很高。在肾素血管紧张素系统抑制的基础上增加脑啡肽酶抑制，可能导致不良LV重塑的更大衰减，这是由于具有血管舒张、抗肥大、抗纤维化和交感神经溶解作用的脑啡肽酶底物水平增加。我们进行了一项前瞻性、多中心、随机、双盲、活性对照试验，比较沙库比曲/缬沙坦97/103 mg每日2次与缬沙坦160 mg每日2次在心肌梗死后≥3个月、左室射血分数≤40%、服用肾素血管紧张素系统抑制剂（相当于雷米普利≥2.5 mg每日2次）和β受体阻滞剂（除非有禁忌症或不耐受）的患者中的疗效。排除了纽约心脏协会分级≥II级或有心力衰竭体征和症状的患者。主要结局是使用心脏磁共振成像测量的LV收缩末期容积指数从基线到52周的变化。次要结局包括LV重构的其他磁共振成像测量值、NT-proBNP（N末端B型利钠肽前体）和高敏心肌肌钙蛋白I的变化以及患者总体变化评估问卷。从2018年7月至2019年6月，我们随机分配了93例具有以下特征的患者：平均年龄为60.7±10.4岁;心肌梗死中位时间为3.6年（四分位距为1.2-7.2）;平均LV射血分数为36.8%±7.1%;中位NT-proBNP为230 pg/mL（四分位距为124-404）。与缬沙坦相比，沙库巴曲/缬沙坦未显著降低LV收缩末期容积指数;校正后的组间差异为-1.9 mL/m2（95% CI，-4.8至1.0）; P=0.19。NT-proBNP、高敏心肌肌钙蛋白I、LV舒张末期容积指数、左心房容积指数、LV射血分数、LV质量指数或患者总体变化评估无显著组间差异。在心肌梗死后晚期无症状左室收缩功能不全患者中，与缬沙坦相比，沙库巴曲/缬沙坦治疗没有显著的逆转重构作用。URL：https://www.clinicaltrials.gov;唯一标识符：NCT 03552575。
Supplemental Digital Content is available in the text. Patients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects. We performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103 mg twice daily with valsartan 160 mg twice daily in patients ≥3 months after myocardial infarction with a LV ejection fraction ≤40% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril ≥2.5 mg twice daily) and a β-blocker unless contraindicated or intolerant. Patients in New York Heart Association class ≥II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire. From July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7±10.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2–7.2); mean LV ejection fraction, 36.8%±7.1%; and median NT-proBNP, 230 pg/mL (interquartile range, 124–404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, –1.9 mL/m2 (95% CI, –4.8 to 1.0); P=0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change. In patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03552575.