Statins to mitigate cardiotoxicity in cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis
Mary Obasi, Arielle Abovich, Jacqueline B. Vo, Yawen Gao, Stefania Papatheodorou, Anju Nohria, Aarti Asnani, Ann H. Partridge
Abstract
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, $${ }I^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mrow/> <mml:msup> <mml:mi>I</mml:mi> <mml:mn>2</mml:mn> </mml:msup> </mml:mrow> </mml:math> = 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, $$I^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mi>I</mml:mi> <mml:mn>2</mml:mn> </mml:msup> </mml:math> = 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, $$I^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mi>I</mml:mi> <mml:mn>2</mml:mn> </mml:msup> </mml:math> = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82–11.68, p = 0.024, $$I^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mi>I</mml:mi> <mml:mn>2</mml:mn> </mml:msup> </mml:math> = 80.9%]. We were unable to explore publication bias due to the small number of studies. Conclusion 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.