Protective Effects of ACEI/ARB on Left Ventricular Function in Anthracycline-Induced Chronic Cardiotoxicity: A Meta-Analysis of Randomized Controlled Trials

Abstract

<b><i>Purpose:</i></b> Cardiotoxicity is an important side effect of anthracycline. Cardioprotective drugs for anthracycline remain inconclusive. We attempted to determine the role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) in the prevention of anthracycline-induced cardiotoxicity. <b><i>Hypothesis:</i></b> Prophylactic use of ACEI/ARB reduces the clinical or subclinical cardiotoxicity of anthracycline. <b><i>Methods:</i></b> Randomized controlled trials (RCTs) of ACEI/ARB in the prevention of anthracycline-induced cardiotoxicity were obtained by searching Pubmed, Embase, Web of Science, and Cochrane databases. 7 studies were finally included. A meta-analysis was performed on the 7 studies. The end points were changes in left ventricle ejection fraction (LVEF), early and late diastolic peak velocity ratio (<i>E</i>/<i>A</i>), and occurrence of hypotensive events. <b><i>Results:</i></b> Prophylactic use of ACEI/ARB has potential benefits for anthracycline-induced cardiotoxicity. LVEF was better preserved in the experimental group than in the control group (weighted mean difference [WMD] −3.16%, 95% confidence interval [CI] [−5.78, −0.54], <i>p</i> = 0.02). Follow-up time, tumor type, drug type, and geographical region did not affect the results. There was no significant benefit of <i>E</i>/<i>A</i> in the experimental group (WMD 0.02, 95% CI [−0.06, 0.11], <i>p</i> = 0.58), and no increase in the incidence of hypotension (risk ratio 3.79, 95% CI [0.44, 32.89], <i>p</i> = 0.23). <b><i>Conclusions:</i></b> We found that prophylactic use of ACEI/ARB reduced the clinical or subclinical cardiotoxicity of anthracycline, and the increase in hypotensive events was not significant. Due to the relatively small number of clinical studies and participants, more related studies are necessary to further verify our results.

Baseline blood pressure and development of cardiotoxicity in patients treated with anthracyclines: A systematic review

“…Based on current clinical guidance, patients presenting as pre-hypertensive would not be currently eligible for antihypertensive drug therapy [ 7 , 8 ]. Clinical trials are however underway to assess the potential use of antihypertensive angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB) in the prevention of anthracycline-associated heart failure [ 14 ]. In several of these trials, whereas patients receiving antihypertensive medications are excluded, patients exhibiting pre-hypertension are included based on the fact their BPs are within the ‘normal’ range.…”

“…In several of these trials, whereas patients receiving antihypertensive medications are excluded, patients exhibiting pre-hypertension are included based on the fact their BPs are within the ‘normal’ range. Preliminary results to date are encouraging with ACEi/ARB demonstrating a protective effect and reducing the cardiotoxic effects of anthracyclines [ 14 ]. However, due to the early stages of these studies and subsequent limited data available, it is not yet ascertained whether ACEi/ARB can mitigate anthracycline-associated heart failure or indeed the contribution played by pre-hypertension in development of these adverse effects.…”

“…The additive effects of anthracycline exposure and elevated blood pressure overwhelm endogenous cardiac compensation mechanisms, which subsequently drive progressive heart failure [ 12 ]. This association between cardiotoxicity and hypertension is supported by the observation that concomitant administration of antihypertensive angiotensin converting enzyme inhibitors (ACEi) during anthracycline therapy protects left-ventricular (LV) function and ejection fraction (EF) [ [13] , [14] , [15] ]. It however remains to be determined whether these effects extend outside of hypertension and also encompass pre-hypertension and high-normal BP.…”

Current perspectives of cardio‐oncology: Epidemiology, adverse effects, pre‐treatment screening and prevention strategies

“…56 The protective mechanism of ACEI includes the inhibition of ventricular remodelling. 57 Gupta et al assessed the role of enalapril in a randomised, double-blind, clinical trial in which measurements of LVEF (2-D echocardiography) and cardiac biochemical markers (cTnI, proBNP and CK-MB) were performed. After 6 months of treatment, significant differences were detected in the LVEF and mean levels of cTnI and proBNP.…”

Cardiovascular Disease, Cancer, and Multimorbidity Interactions: Clinical Implications

“…Eliminating risk factors for CVD and moderate aerobic exercise may contribute to this effort [17, 36]. The use of β-blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers to prevent cardiotoxicity still is controversial and is based on limited studies [36, 42]. More recently, it has been suggested that statins may decrease cardiotoxicity related to chemotherapy in patients with breast cancer [43].…”