Cardioprotective Effect of Metoprolol and Enalapril in Doxorubicin-treated Lymphoma Patients: a Prospective, Parallel-group, Randomized, Controlled Study with 36-month Follow-up

Anthracyclines have contributed to a marked increase in survival in different types of cancer [1,2]. Unfortunately, they are associated with dose-dependent cardiotoxicity and heart failure (HF) [3–8]. Change to a weekly dosage schedule with slow infusions has been tested, a strategy that requires more frequent hospital visits and increased storage resources[7,9]. Liposomal anthracycline formulations with reduced drug exposure and lower plasma concentrations may still be cardiotoxic at higher cumulative doses [10]. Beta-blockers and angiotensin converting enzyme(ACE) inhibitors have been shown to reduce anthracycline-induced cardiotoxicity,but have not been tested in long-term prospective, randomized,controlled studies with well defined cardiotoxicity criteria and careful cardiac function monitoring [11–16]. We investigated doxorubicin-induced clinical or subclinical cardiotoxicity in lymphoma patients after concomitant prophylactic therapy with metoprolol or enalapril or no concomitant treatment. We examined whether cardiotoxicity was related to the treatment or any other variable. We found that HF was less frequent under concomitant treatment than no treatment, especially in the metoprolol group, but the differences were not significant. No association was found between the presence of cardiotoxicity and concomitant treatment or other variable apart of age that had a significant impact. The marginal benefit seen with metoprolol should be investigated further.