STOP-CA: Statins to prevent Cardiotoxicity from Anthracyclines

7.项目摘要/摘要 非霍奇金淋巴瘤(NHL)患者的生存率由于早期的联合治疗而有所改善 诊断、改进的特征和更好的治疗。蒽环类药物是大多数 NHL患者的标准化疗方案有助于提高存活率。 然而，由于心脏毒性的广为人知和频繁发生，限制了蒽环类药物的使用。 这表现为左心室射血分数(LVEF)降低，导致充血性心力衰竭。 与接受以蒽环类药物为基础的化疗的其他患者相比，NHL患者处于 充血性心力衰竭的风险最高。在动物研究中，他汀类药物可减少心肌纤维化和细胞死亡 在他汀类药物和小型临床研究后，他汀类药物保留了左心室射血分数。因此，在这个随机化的多- 中心安慰剂对照临床试验，他汀类药物预防蒽环类药物心脏毒性(STOP-CA)， 我们将在270名患者开始化疗12个月后确定他汀类药物是否保留了LVEF。 非霍奇金淋巴瘤正在接受以蒽环类药物为基础的化疗。我们将测试他汀类药物对心脏的影响 磁共振(CMR)得出的LVEF作为CMR得出的LVEF是非侵入性的黄金标准 测量左心室射血分数。所有测量将在岩心成像实验室由专家评审员进行 使用标准化协议对所有其他数据视而不见。这项研究不能用来检测 临床事件；然而，他汀类药物治疗已被回顾显示可减少心力衰竭 住院人数，这将是后续研究的关键目标，我们将收集这些数据。我们还提议 使用CMR成像提供的附加组织定征来测试他汀类药物治疗对 蒽环类药物诱导的心肌纤维化以及纤维化是否可以预测LVEF的下降。最后，我们会 使用超声心动图和血浆测量的心肌应变(心功能的敏感指标) 肌钙蛋白水平(反映心肌损伤)，这两个广泛可用的和可扩展的参数，用于早期识别 治疗期间，高危非霍奇金淋巴瘤患者左心室射血分数下降，并测试他汀类药物是否有益 对心肌损伤和早期左心功能不全的影响。在这项建议完成后，我们将拥有 他汀类药物对非霍奇金淋巴瘤患者应用他汀类药物治疗所致左心功能不全的影响 他们的安全性和确定的NHL患者心脏毒性的高风险。

7. Project Summary/Abstract Survival among patients with non-Hodgkin's Lymphoma (NHL) has improved due to a combination of earlier diagnosis, improved characterization and better treatments. Anthracyclines are an integral part of most standard chemotherapy regimens for patients with NHL and have contributed to this improved survival. However, the use of anthracyclines is limited by the well recognized and frequent occurrence of cardiotoxicity, that manifests itself as a reduction in left ventricular ejection fraction (LVEF) leading to congestive heart failure. In comparison to other patients receiving anthracycline-based chemotherapy, patients with NHL are at the highest risk of congestive heart failure. In animal studies, statins reduced myocardial fibrosis and cell death after anthracyclines and in small clinical studies statins preserved LVEF. Therefore, in this randomized multi- center placebo-controlled clinical trial, Statins TO Prevent the Cardiotoxicity from Anthracyclines (STOP-CA), we will determine whether statins preserve LVEF 12 months after the initiation of chemotherapy in 270 patients with NHL undergoing anthracycline-based chemotherapy. We will test the effect of statin therapy on cardiac magnetic resonance (CMR)-derived LVEF as CMR-derived LVEF is the gold-standard for non-invasive measurement of LVEF. All measurements will be performed in a core imaging laboratory by expert reviewers blinded to all other data using a standardized protocol. This study is not powered to detect a difference in clinical events; however, as statin therapy has been shown retrospectively to reduce heart failure hospitalizations, and this will be a key goal of subsequent studies, we will capture this data. We also propose to use the additive tissue characterization available with CMR imaging to test the effect of statin therapy on anthracycline-induced myocardial fibrosis and whether fibrosis predicts the decrease in LVEF. Finally, we will use myocardial strain (a sensitive index of cardiac function) measured using echocardiography and plasma levels of troponin (reflecting myocardial injury), both widely available and scalable parameters, to identify early during treatment NHL patients at high risk of LVEF decline and to test whether statin therapy has beneficial effects on myocardial injury and early LV dysfunction. At the completion of this proposal, we will have characterized the effect of statins on anthracycline-induced LV dysfunction in patients with NHL, established their safety and identified patients with NHL at high risk of cardiotoxicity.