Statins to mitigate cardiotoxicity in cancer patients treated with anthracyclines and/or trastuzumab: A systematic review and meta-analysis

Abstract Purpose: Cardiotoxicity affects 5-16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies. Methods: A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran’s Q test and the I 2 test. Results: Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR=0.46, 95% CI (0.27-0.78), p=0.004, =0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR=0.49, 95% CI (0.17-1.45), p=0.20, =5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD)=6.14%, 95% CI (2.75-9.52), p<0.001, =74.7%] and RCTs [WMD=6.25%, 95% CI (0.82-11.68, p=0.024, =80.9%]. We were unable to explore publication bias due to the small number of studies. Conclusions: This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab.Trial Registration Number and Date of Registration: PROSPERO: CRD42020140352 on 7/6/2020.