Cardiology Department, Clinica Alemana de Santiago, Santiago, Chile.
Cardiology Department, Hospital del Salvador, Santiago, Chile.
Trials. 2020 Feb 4;21(1):137. doi: 10.1186/s13063-019-3963-6.
Anthracycline-induced cardiotoxicity (AIC), a condition associated with multiple mechanisms of damage, including oxidative stress, has been associated with poor clinical outcomes. Carvedilol, a β-blocker with unique antioxidant properties, emerged as a strategy to prevent AIC, but recent trials question its effectiveness. Some evidence suggests that the antioxidant, not the β-blocker effect, could prevent related cardiotoxicity. However, carvedilol's antioxidant effects are probably not enough to prevent cardiotoxicity manifestations in certain cases. We hypothesize that breast cancer patients taking carvedilol as well as a non-hypoxic myocardial preconditioning based on docosahexaenoic acid (DHA), an enhancer of cardiac endogenous antioxidant capacity, will develop less subclinical cardiotoxicity manifestations than patients randomized to double placebo.
METHODS/DESIGN: We designed a pilot, randomized controlled, two-arm clinical trial with 32 patients to evaluate the effects of non-hypoxic cardiac preconditioning (DHA) plus carvedilol on subclinical cardiotoxicity in breast cancer patients undergoing anthracycline treatment. The trial includes four co-primary endpoints: changes in left ventricular ejection fraction (LVEF) determined by cardiac magnetic resonance (CMR); changes in global longitudinal strain (GLS) determined by two-dimensional echocardiography (ECHO); elevation in serum biomarkers (hs-cTnT and NT-ProBNP); and one electrocardiographic variable (QTc interval). Secondary endpoints include other imaging, biomarkers and the occurrence of major adverse cardiac events during follow-up. The enrollment and follow-up for clinical outcomes is ongoing.
We expect a group of anthracycline-treated breast cancer patients exposed to carvedilol and non-hypoxic myocardial preconditioning with DHA to show less subclinical cardiotoxicity manifestations than a comparable group exposed to placebo.
ISRCTN registry, ID: ISRCTN69560410. Registered on 8 June 2016.
蒽环类药物诱导的心脏毒性（AIC）是一种与多种损伤机制相关的疾病，包括氧化应激，与不良的临床结局相关。卡维地洛是一种具有独特抗氧化特性的β受体阻滞剂，已被提出作为预防 AIC 的一种策略，但最近的试验对其疗效提出了质疑。一些证据表明，预防相关心脏毒性的可能是抗氧化作用，而不是β受体阻滞剂作用。然而，在某些情况下，卡维地洛的抗氧化作用可能不足以预防心脏毒性表现。我们假设，与随机分配至双安慰剂组的患者相比，接受卡维地洛治疗以及基于二十二碳六烯酸（DHA）的非缺氧性心肌预处理的乳腺癌患者将表现出较少的亚临床心脏毒性表现，DHA 是一种增强心脏内源性抗氧化能力的物质。
方法/设计：我们设计了一项前瞻性、随机对照、双臂临床试验，纳入了 32 名患者，以评估非缺氧性心脏预处理（DHA）加卡维地洛对接受蒽环类药物治疗的乳腺癌患者亚临床心脏毒性的影响。该试验包括四个主要终点：心脏磁共振（CMR）测定的左心室射血分数（LVEF）变化；二维超声心动图（ECHO）测定的整体纵向应变（GLS）变化；血清生物标志物（hs-cTnT 和 NT-ProBNP）升高；以及一个心电图变量（QTc 间期）。次要终点包括其他影像学、生物标志物以及随访期间主要不良心脏事件的发生。目前正在进行临床结局的入组和随访。
我们预计，与接受安慰剂的可比组相比，接受卡维地洛和 DHA 非缺氧性心肌预处理的蒽环类药物治疗的乳腺癌患者组表现出较少的亚临床心脏毒性表现。
ISRCTN 注册，ID：ISRCTN69560410。于 2016 年 6 月 8 日注册。
