Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer
Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer
复制标题
DOI：
10.1016/j.jacc.2019.03.495
复制
发表时间：
2019-06-11
影响因子：
24
通讯作者：
Munster, Pamela N.
中科院分区：
文献类型：
--
作者：
Guglin, Maya;Krischer, Jeffrey;Munster, Pamela N.
背景曲妥珠单抗对人表皮生长因子受体2型（HER 2）阳性乳腺癌非常有效，但与左心室射血分数下降有关。（左心室射血分数降低> 10%，或如果低于50%则> 5%）并限制治疗中断。在2年的时间内，对接受曲妥珠单抗治疗12个月的HER 2阳性乳腺癌患者的心脏毒性和治疗中断进行了评价。患者分层蒽环类药物的使用，然后随机接受赖诺普利，卡维地洛，或placebo. Results研究包括468名妇女，年龄51 +/- 10.7岁。对于整个队列，3组的心脏毒性相当，安慰剂组有32%的患者发生心脏毒性，卡维地洛组有29%，赖诺普利组有30%。对于接受蒽环类药物治疗的患者，安慰剂组（47%）的事件发生率高于赖诺普利组（37%）和卡维地洛组（31%）。卡维地洛（危害比：0.49; 95%可信区间：0.27 - 0.89; p = 0.009）和赖诺普利（危害比：0.53; 95%可信区间：0.30 - 0.94; p = 0.015）的无毒性生存期均长于安慰剂。在整个队列中，以及在蒽环类药物的手臂，积极治疗与血管紧张素转换酶抑制剂或β-受体阻滞剂的患者经历了较少的中断曲妥珠单抗比安慰剂。结论在与HER 2阳性乳腺癌患者治疗曲妥珠单抗，赖诺普利和卡维地洛预防心脏毒性的患者接受蒽环类药物。对于此类患者，应考虑使用赖诺普利或卡维地洛，以尽量减少曲妥珠单抗的中断。(C)2019年由美国心脏病学会基金会。
BACKGROUND Trastuzumab is highly effective for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer but is associated with a decline in left ventricular ejection fraction.OBJECTIVES The purpose of this study was to determine whether angiotensin-converting enzyme inhibitors or beta-blockers reduce the rate of trastuzumab-induced cardiotoxicity (left ventricular ejection fraction decrease > 10%, or > 5% if below 50%) and limit treatment interruptions.METHODS In this double-blind, multicenter, placebo-controlled trial, cardiotoxicity and treatment interruptions in patients with HER2-positive breast cancer treated with trastuzumab for 12 months were evaluated over a 2-year period. Patients were stratified by anthracycline use and then randomized to receive lisinopril, carvedilol, or placebo.RESULTS The study included 468 women, age 51 +/- 10.7 years. For the entire cohort, cardiotoxicity was comparable in the 3 arms and occurred in 32% of patients on placebo, 29% on carvedilol, and 30% on lisinopril. For patients receiving anthracyclines, the event rates were higher in the placebo group (47%) than in the lisinopril (37%) and the carvedilol (31%) groups. Cardiotoxicity-free survival was longer on both carvedilol (hazard ratio: 0.49; 95% confidence interval: 0.27 to 0.89; p = 0.009) and lisinopril (hazard ratio: 0.53; 95% confidence interval: 0.30 to 0.94; p = 0.015) than on placebo. In the whole cohort, as well as in the anthracycline arm, patients on active therapy with either angiotensin-converting enzyme inhibitor or beta-blockers experienced fewer interruptions in trastuzumab than those on placebo.CONCLUSIONS In patients with HER2-positive breast cancer treated with trastuzumab, both lisinopril and carvedilol prevented cardiotoxicity in patients receiving anthracyclines. For such patients, lisinopril or carvedilol should be considered to minimize interruptions of trastuzumab. (C) 2019 by the American College of Cardiology Foundation.