STOP-CA: Statins to prevent Cardiotoxicity from Anthracyclines

7.项目总结/摘要 非霍奇金淋巴瘤（NHL）患者的生存率有所改善，这是由于早期联合 诊断，改善表征和更好的治疗。蒽环类药物是大多数 NHL患者的标准化疗方案，并有助于提高生存率。 然而，蒽环类药物的使用受到公认的和频繁发生的心脏毒性的限制， 其表现为左心室射血分数（LVEF）降低，导致充血性心力衰竭。 与其他接受蒽环类化疗的患者相比，NHL患者的生存率为100%。 充血性心力衰竭的风险最高在动物研究中，他汀类药物减少了心肌纤维化和细胞死亡 在蒽环类药物治疗后，在小型临床研究中，他汀类药物可维持LVEF。因此，在这个随机的多- 中心安慰剂对照临床试验，他汀类药物预防蒽环类药物毒性（STOP-CA）， 我们将在270例患者中确定他汀类药物是否能在化疗开始后12个月保持LVEF 接受蒽环类化疗的NHL患者我们将测试他汀类药物治疗对心脏的影响， 磁共振（CMR）推导的LVEF是无创性LVEF的金标准， 测量LVEF。所有测量将由专家评审员在核心成像实验室进行 使用标准化方案对所有其他数据设盲。本研究没有把握度检测以下方面的差异： 临床事件;然而，由于他汀类药物治疗已被回顾性证明可减少心力衰竭， 住院治疗，这将是后续研究的关键目标，我们将收集这些数据。我们亦建议 使用CMR成像提供的附加组织表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预示LVEF降低。最后我们将 使用超声心动图和血浆测量的心肌应变（心脏功能的敏感指数） 肌钙蛋白水平（反映心肌损伤），这两个广泛可用和可扩展的参数，以确定早期 在治疗过程中，NHL患者LVEF下降的高风险，并测试他汀类药物治疗是否有益 对心肌损伤和早期LV功能障碍的影响。在完成这项建议后，我们将有 描述了他汀类药物对非霍奇金淋巴瘤患者蒽环类药物诱导的左室功能障碍的影响， 他们的安全性和确定的NHL患者在心脏毒性的高风险。

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.