使用 EMPAgliflozin 预防 CARDiotoxicity:EMPACARD - PILOT 试验。

IF 3.2 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Andrés J Daniele, Vanesa Gregorietti, Diego Costa, Teresa López-Fernández
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引用次数: 0

摘要

背景:蒽环类化疗是治疗乳腺癌、淋巴瘤和肉瘤等多种常见癌症的基础疗法。然而,蒽环类药物诱发的心脏毒性仍是一个令人严重关切的问题,通常表现为心脏功能下降,最终导致心力衰竭(HF)或无症状左心室功能障碍,患者比例高达 10-15%。方法:EMPACARD-PILOT 试验是一项前瞻性病例对照研究,涉及计划接受蒽环类药物化疗的乳腺癌患者,化疗方案为 4 周期 60 mg/m2 多柔比星。我们使用 HFA/ICOS 风险评分来确定心脏毒性高风险或极高风险患者。糖尿病或稳定型射血分数保留型心力衰竭(HFpEF)患者在使用蒽环类药物前七天开始服用恩格列净(每天10毫克),并持续服用六个月。不符合上述标准的患者作为对照组。主要终点是癌症治疗相关心功能不全(CTRCD)的发生率。CTRCD的定义是在研究期间的任何时间点,左心室射血分数(LVEF)下降至少10%,最终值低于50%,或者整体纵向应变(GLS)比基线下降至少15%。次要终点包括死亡率和因心血管原因或临床心力衰竭导致的住院治疗。探索性终点包括血清肌钙蛋白和NT-proBNP水平的升高以及肾小球滤过率(GFR)的降低。追踪的安全性终点包括酮症酸中毒、低血糖、败血症、中性粒细胞减少性发热和尿路感染:在注册期间,共对 785 名乳腺癌患者进行了分析。其中 107 人符合纳入标准,76 人随后提供了知情同意书。研究中,恩格列净组(38 人)和对照组(38 人)的依从性相当,均为 81.5%。62名患者的随访数据显示,与对照组相比,恩格列净组患者6个月内的主要结局显著降低(6.5% vs. 35.5%,p = 0.005),相对风险为0.18(95% CI:0.04-0.75)。与对照组相比,使用empagliflozin治疗还能显著保持随访6个月时的射血分数(56.8% ± 5.8% vs. 53.7% ± 6.7,p = 0.029)。然而,在NT-proBNP、cTnI、临床心衰、GFR或死亡率/心衰住院率方面,两组之间没有明显差异:结论:在接受蒽环类药物治疗的高危患者中,恩格列净可降低CTRCD的发生率。这些数据应作为临床试验的基础,以检验 SGLT2 抑制剂是否能降低这类患者的心衰发生率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Use of EMPAgliflozin in the prevention of CARDiotoxicity: the EMPACARD - PILOT trial.

Background: Anthracycline-based chemotherapy represents a cornerstone treatment for a number of common cancers, including breast cancer, lymphoma, and sarcoma. However, anthracycline-induced cardiotoxicity remains a significant concern, often presenting as a decline in cardiac function which can ultimately lead to heart failure (HF) or asymptomatic left ventricular dysfunction, in up to 10-15% of patients.Sodium-glucose transport protein 2 inhibitor (SGLT2i) therapies have been demonstrated to reduce the incidence of HF in high-risk non-cancer patients. Preliminary retrospective data suggest their role in mitigating the incidence of HF during or after anthracycline treatment METHODS: The EMPACARD-PILOT trial was a prospective case‒control study involving breast cancer patients scheduled to undergo anthracycline-based chemotherapy in a 4-cycle protocol of 60 mg/m2 doxorubicin. We used the HFA/ICOS risk score to identify patients at high or very high risk of cardiotoxicity. Patients with diabetes mellitus or stable heart failure with preserved ejection fraction (HFpEF) were prescribed empagliflozin (10 mg per day), starting seven days before the administration of anthracyclines and continuing for a period of six months. Those not meeting these criteria served as controls. The primary endpoint was cancer therapy-related cardiac dysfunction (CTRCD) incidence. CTRCD was defined as either a decrease in left ventricular ejection fraction (LVEF) of at least 10% to a final value below 50% or a reduction in global longitudinal strain (GLS) of at least 15% from baseline at any point during the study. The secondary endpoints included mortality and hospitalization due to cardiovascular causes or clinical heart failure. Exploratory endpoints included increases in serum troponin and NT-proBNP levels and a decrease in the glomerular filtration rate (GFR). The safety endpoints tracked includedketoacidosis, hypoglycemia, sepsis, neutropenic fever, and urinary tract infections.

Results: During the enrollment period, 785 breast cancer patients were analysed. Of these, 107 met the inclusion criteria, and 76 subsequently provided informed consent. The study was conducted with comparable adherence rates of 81.5% in both the empagliflozin group (n = 38) and the control group (n = 38). The follow-up data from 62 patients revealed a significant reduction in the primary outcome within 6 months for the empagliflozin group compared with the control group (6.5% vs. 35.5%, p = 0.005), with a relative risk of 0.18 (95% CI: 0.04-0.75). Compared with the control treatment, treatment with empagliflozin also significantly preserved the ejection fraction at 6 months follow-up (56.8% ± 5.8% vs. 53.7% ± 6.7, p = 0.029). However, there were no significant differences between the groups in terms of NT-proBNP, cTnI, clinical heart failure, GFR, or mortality/hospitalization due to heart failure.

Conclusion: Empagliflozin is associated with reduced incidence of CTRCD in high-risk patients treated with anthracyclines. These data should serve as the foundation for a clinical trial to test whether SGLT2 inhibitors can reduce the incidence of heart failure in this patient group.

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来源期刊
Cardio-oncology
Cardio-oncology Medicine-Cardiology and Cardiovascular Medicine
CiteScore
5.00
自引率
3.00%
发文量
17
审稿时长
7 weeks
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