Cardioprotective effects of prophylactic ACE inhibitors in anthracycline-induced cardiotoxicity: a systematic review and meta-analysis of randomized trials

This study aims to evaluate the efficacy of angiotensin-converting enzyme inhibitors (ACEi) in preventing anthracycline-induced cardiotoxicity in patients undergoing anthracycline-based chemotherapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing ACEi to standard treatment/placebo for cardiotoxicity prevention in patients undergoing anthracycline-based chemotherapy. We pooled outcomes of echocardiographic and cardiac biomarker changes. A random-effects model was used for all outcomes. We included 7 RCTs with 686 patients, of whom 346 (50%) received prophylaxis with ACEi. The most common malignancy was breast cancer, and the follow-up ranged from 6 to 31 months. Prophylactic use of ACEi was associated with a significantly smaller reduction in left ventricular ejection fraction (LVEF) compared to the control group (mean difference -5% [95% CI -8% - -2%]; p<0.010). Subgroup analysis limited to studies excluding trastuzumab from the chemotherapy regimens showed no significant difference (MD -7% [95% CI - 16% - 2%]; p=0.110). In contrast, in studies including trastuzumab-containing regimens, ACEi demonstrated a statistically significant effect in limiting LVEF reduction (MD -3%, [95% CI -4 - -1]; p<0.010). Diastolic function (E/A ratio) changes (MD 0.0 [95% CI -0.1 - 0.09]; I2=36.3%) and relative risk of increased troponin I at follow-up (RR 0.58 [95% CI 0.17 - 1.94]; I2=69.6%) were not statistically significant. Prophylactic ACEi administration in patients undergoing anthracycline-based chemotherapy was associated with a smaller decline in LVEF. This protective role may be more relevant in patients also receiving trastuzumab. More powered and longer follow-up studies are needed to confirm these findings.