Effects of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use on cancer therapy-related cardiac dysfunction: a meta-analysis of randomized controlled trials.

Abstract

Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) may attenuate cancer therapy-related cardiac dysfunction (CTRCD). However, results of the previous studies were not consistent. We performed a meta-analysis to evaluate the influence of ACEI/ARB on CTRCD. Randomized controlled trials (RCTs) were obtained by searching of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Nine RCTs with 1095 cancer patients that underwent chemotherapy with anthracycline and/or trastuzumab were included. Using of ACEI/ARB significantly preserved left ventricular ejection fraction (LVEF, weighed mean difference = 4.24%, p = 0.002) compared with controls. Subgroup analyses showed that the benefits of ACEI/ARB on LVEF following chemotherapy were consistent and independent of study characteristics including study design, sample size, cancer type, chemotherapy protocols, preventative medications of ACEI or ARB, methods for LVEF measurement, and follow-up durations. The benefits on LVEF following chemotherapy were more remarkable in studies using ACEI and followed ≤ 12months (p for subgroup difference = 0.04 and 0.02). Use of ACEI/ARB did not significantly reduce the risk of cardiotoxicity events (risk ratio [RR] = 0.63, p = 0.22) but increased the risk of hypotension in these patients (RR = 3.94, p = 0.008). These results indicated that using of ACEI/ARB may moderately attenuate CTRCD following chemotherapy with anthracycline and/or trastuzumab. Large-scale RCTs are needed to evaluate whether the benefits of ACEI/ARB on LVEF are clinically relevant.