Prevention of Cancer Therapy-Related Cardiac Dysfunction With Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blocker: A Systematic Review of Randomised Controlled Trials

Abstract

Cancer therapy-related cardiac dysfunction (CTRCD) is an important complication of selected chemotherapy agents associated with decline in left ventricular ejection fraction (LVEF) or clinical heart failure. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have established benefits in heart failure with reduced ejection fraction, but their efficacy for preventing and treating CTRCD remains controversial. This systematic review aimed to assess the efficacy of ACEI and ARB in the prevention of CTRCD. PubMed, Embase, and Cochrane were systematically searched. Studies of interest were randomised controlled trials of patients with normal LVEF and active malignancy receiving chemotherapy, randomised to receive either an ACEI or ARB compared with a control group. The outcome of interest was the change in LVEF from baseline. Death, clinical heart failure, and adverse drug reactions were also recorded. A total of 3,731 search records were screened and 12 studies were included, comprising a total of 1,645 participants. Nine studies assessed the prevention of anthracycline-induced CTRCD, of which five studies showed a beneficial effect (1%–14% higher LVEF in treated groups), while four studies showed no beneficial effect. Three studies assessed the prevention of trastuzumab-induced CTRCD, of which one study showed a beneficial effect (4% higher LVEF) in a subset of participants. There is mixed evidence regarding the efficacy of ACEI or ARB in preventing the decline in LVEF in patients undergoing chemotherapy with either anthracyclines or trastuzumab, with a small but clinically meaningful benefit observed in some studies.