Can ACEI/ARB prevent the cardiotoxicity caused by chemotherapy in early-stage breast cancer?—a meta-analysis of randomized controlled trials

Abstract

Background: Administration of anthracycline-based chemotherapy with or without trastuzumab is recognized as standard care for breast cancer, but it is associated with a decline in left ventricular ejection fraction (LVEF). Angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB) might decrease this cardiac dysfunction caused by the anti-cancer therapy. We sought to evaluate the prophylactic effects of the cardioprotective agents ACEI/ARB for early-stage breast cancer. Methods: We systematically searched the electronic databases Cochrane, PubMed, and Embase for randomized controlled trials (RCTs) evaluating the effect of ACEI/ARB. This meta-analysis calculated weighted mean differences with 95% CI, for ejection fraction and pooled odds ratios (OR) with 95% CI, for cardiac events. Pooled analyses were used in a random-effect model. The primary endpoint was the change of LVEF in the ACEI/ARB group versus the control group from baseline through completion of the studies. Results: our meta-analysis includes 5 studies encompassing 702 early-stage breast cancer patients. There was statistically significant diversity in the magnitude of the change of mean LVEF in patients receiving ACEI/ARB compared with control groups, with a mean difference of 4.08% (95% CI: 0.8% to 7.35%, P=0.01). However, regarding patient outcomes, ACEI/ARB did not significantly reduce the risk of cardiac events (OR 0.91, 95% CI: 0.62 to 1.34, P=0.64) or increase the incidence of hypotension events as compared with controls (OR 2.72, 95% CI: 0.69 to 10.73, P=0.15). Conclusions: Our study suggests that ACEI/ARB significantly attenuate the cardiac dysfunction caused by anthracycline-based chemotherapy and/or trastuzumab. Further studies are required to confirm the effectiveness of this cardioprotective agent.