Sacubitril-Valsartan for the Prevention of Anthracycline Cardiotoxicity in Patients With Elevated Cardiac Troponin I Concentration During Chemotherapy: A Double-Blind Randomized Placebo-Controlled Clinical Trial: The SARAH Trial.

Experimental evidence suggests cardioprotective properties.

实验性证据表明其具有心脏保护特性。

This study evaluated the efficacy of sacubitril-valsartan in reducing cardiotoxicity in patients with increased cardiac troponin I concentrations during anthracycline chemotherapy.

本研究评估了在葱环类化疗期间，心脏肌钙蛋白I浓度升高患者中使用沙库巴曲-缬沙坦减少心毒性的作用。

Methods

This randomized, double-blind, placebo-controlledtrial enrolled 114 patients with elevated cardiac troponin I levels during anthracycline treatment.

这项随机、双盲、安慰剂对照试验招募了114名在葱环类治疗期间心脏肌钙蛋白I水平升高的患者。

Participants were randomized 1:1 to receive either sacubitril-valsartan or placebo for 6 months, with a target dose of 97/103 mg twice daily.

参与者按1:1的比例随机接受沙库巴曲-缬沙坦或安慰剂治疗6个月，目标剂量为每日两次97/103毫克。

The primary end point was the occurrence of a >15% reduction in the global longitudinal strain from baseline to 6 months.

主要终点是基线至6个月期间全球纵向应变减少超过15%的发生。

Secondary end points included changes in biomarkers, echocardiographic and cardiac magnetic resonance parameters, and adverse events.

次要终点包括生物标志物、超声心动图和心脏磁共振参数的变化，以及不良事件。

This trial was initially conceptualized as a pilot investigation because of its exploratory nature.

由于其探索性质，这项试验最初被构想为一项试点调查。

Data were analyzed according to the intention-to-treatprinciple.

数据根据意向治疗原则进行分析。

Results

Among the randomized patients, 90% were women, and 80.7% had breast cancer.

在随机分配的患者中，90%为女性，80.7%患有乳腺癌。

The primary end point occurred in 4 patients (7%) in the sacubitril-valsartan group and 14 patients (25%) in the placebo group (odds ratio, 0.23 [95% CI, 0.07-0.75]; P=0.015).

主要终点事件在沙库巴曲缬沙坦组的4名患者（7%）和安慰剂组的14名患者（25%）中发生（比值比，0.23 [95% 置信区间，0.07-0.75]；P=0.015）。

The sacubitril-valsartan group showed a 2.5% improvement in global longitudinal strain, whereas the placebo group experienced a 7.6% decline (P<0.001).

沙库巴曲缬沙坦组的全球纵向应变显示出2.5%的改善，而安慰剂组则下降了7.6%（P<0.001）。

No significant differences in changes in cardiac troponin I or NT-proBNP (N-terminal pro-B-type natriuretic peptide) were observed.

未观察到心脏肌钙蛋白I或NT-proBNP（N末端前体B型利钠肽）的变化有显著差异。

Hypotension (systolic blood pressure <100 mm Hg) occurred more frequently in the sacubitril-valsartan group than in the placebo group (8 cases versus 1 case; P=0.032).

低血压（收缩压<100毫米汞柱）在沙库巴曲-缬沙坦组比安慰剂组更频繁（8例对1例；P=0.032）。

Conclusions

The SARAH trial (Sacubitril-Valsartan for the Prevention of Anthracycline Cardiotoxicity in Patients With Elevated hs-cTnI Concentrations During Chemotherapy) demonstrated the potential of sacubitril-valsartan therapy to reduce the incidenceof left ventricular dysfunction, as assessed by global longitudinal strain, in patients with elevated high-sensitivity cardiac troponin I after anthracycline treatment.

SARAH试验（在接受化疗期间高敏心肌肌钙蛋白I浓度升高患者中预防葱环类药物心脏毒性的沙库巴曲-缬沙坦）显示了沙库巴曲-缬沙坦治疗在降低葱环类药物治疗后高敏心肌肌钙蛋白I升高的患者左心室功能障碍发生率的潜力，通过全球纵向应变进行评估。

registration

URL: https://ensaiosclinicos.gov.br/rg/RBR-5q4gm5b; UTN code: U1111-1274-1961.

URL: https://ensaiosclinicos.gov.br/rg/RBR-5q4gm5b; UTN代码: U1111-1274-1961。