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.
Anthracyclines, a drug used to treat cancers, are toxic to the heart and may lead to heart failure and cardiac death. We will test whether statins, a type of drug typically used to lower cholesterol, can protect the heart during chemotherapy with anthracyclines in patients with non-Hodgkin's lymphoma.
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