July 30, 2023International Journal of Cardiology
Statins as preventive therapy for anthracycline cardiotoxicity: a meta-analysis of randomized controlled trials
Key result
Statins reduce anthracycline-mediated cardiotoxicity ~48% vs placebo.
- RR 0.52
- 95% CI 0.33-0.83
- P=0.01
- n=808
Why the study?
Cardiotoxicity occurs in 5-20% of cancer patients treated with anthracyclines, and the cardio-protective role of statins in this setting requires synthesis of randomized evidence.
Do incretin-based therapies prevent doxorubicin-induced cardiotoxicity in in vivo rodent models?
Key Points
- To evaluate the cardioprotective efficacy and safety of statin therapy in cancer patients receiving anthracycline chemotherapy.
- Systematic search of PubMed and Scopus databases conducted up to May 3rd, 2023, identifying 5 randomized controlled trials comprising 808 patients.
- Evaluated primary and secondary endpoints including incidence of anthracycline-mediated cardiotoxicity, hospitalization for heart failure, post-treatment left ventricular ejection fraction (LVEF), change in LVEF (∆LVEF), and adverse events.
- Statin therapy significantly reduced the incidence of cardiotoxicity compared with placebo (RR 0.52, 95% CI 0.33-0.83, P = 0.01; I2 = 0%).
- Statin-treated patients achieved higher post-treatment LVEF (MD 1.88, 95% CI 0.66-3.1, P < 0.01; I2 = 57.3%) and a more favorable ∆LVEF (MD 2.38, 95% CI -0.03 - +4.79, P = 0.05; I2 = 99%).
- No significant differences were identified between groups regarding hospitalization for heart failure or rates of muscle pain and serious adverse events.
Study Design
Type
Meta-Analysis (n=808)
Structured PICO
Do incretin-based therapies prevent doxorubicin-induced cardiotoxicity in in vivo rodent models?
P
Population
808 cancer patients receiving anthracycline therapy included in a meta-analysis of 5 randomized controlled trials evaluating the cardioprotective role of statins.
I
Intervention
Incretin-based therapies (glucagon-like peptide-1 receptor agonists including liraglutide, exenatide/exendin-4, semaglutide, or dual GIP/GLP-1 RA tirzepatide) administered subcutaneously or intraperitoneally as pretreatment, co-treatment, or post-doxorubicin therapy for 7 days to 6-8 weeks.
C
Comparator
Doxorubicin alone (positive control), with or without non-doxorubicin negative controls.
O
Outcome
Measures of cardiac function (LVEF, LVFS, hemodynamics), circulating and tissue biomarkers of myocardial injury (troponin, CK-MB, BNP), histological outcomes, and mechanistic outcomes (oxidative stress, inflammation, apoptosis).surrogate
Main Result
Relative Risk: 0.52 (95% CI 0.33–0.83)
p-value: p=0.01
Limitations
- Severe heterogeneity affected the analyses for both LVEF and ΔLVEF
- More powered RCTs are needed to fully investigate the impact of statins on prognosis
- Unclear and occasionally high risk of bias in included studies
- Small, single-center experiments
- Heterogeneity in doxorubicin protocols, dosing, and timing preventing quantitative meta-analysis
- Potential for reporting or publication bias
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Statins represent a promise in mitigating CTRCD. Undoubtedly, larger RCTs with adequate follow-up are required to evaluate the impact of statins alone or in combination with the most recent guided-directed medical therapy (ie, sodium-glucose cotransporter 2 inhibitors) on prognosis in patients receiving anthracyclines therapy.”
Implication
Incretin-based therapies demonstrate cardioprotective effects against doxorubicin-induced cardiotoxicity in preclinical rodent models, highlighting a potential therapeutic strategy that requires clinical validation.
Abstract
BACKGROUND Cardiotoxicity occurs in 5-20% of cancer patients who receive anthracyclines. The aim of this study was to pool all the randomized controlled trials (RCTs) investigating the cardio-protective role of statins in patients treated with anthracyclines. METHODS PubMed and Scopus electronic databases were scanned for eligible studies up to May 3rd, 2023. A total of 5 RCTs with 808 patients were included. Efficacy endpoints were the rate of anthracycline-mediated cardiotoxicity, the incidence of hospitalization for heart failure (HF), left ventricular ejection fraction (LVEF) value after anthracycline treatment, and ∆LVEF calculated as the difference in LVEF before and after anthracycline therapy. Safety endpoints [i.e., the incidence of muscle pain and serious adverse events (SAE)] were also assessed. RESULTS On pooled analysis, the statin-treated group had a lower incidence of cardiotoxicity compared to the placebo group [risk ratio (RR) 0.52, 95% confidence Interval (CI) 0.33-0.83, P = 0.01; I2 = 0%], as well as higher mean LVEF [Mean difference (MD) 1.88, 95% CI 0.66-3.1, P < 0.01; I2 = 57.3%)] and a more favorable ∆LVEF during follow-up (MD 2.38, 95% CI -0.03 - +4.79, P = 0.05; I2 = 99%), despite no significant difference in terms of hospitalization for HF and rate of adverse events. Of note, severe heterogeneity affected the analyses for both LVEF and ΔLVEF. CONCLUSIONS The current meta-analysis of all RCTs conducted so far shows an overall beneficial effect of statins on the risk of anthracyclines induced cardiotoxicity and LVEF preservation. No difference was observed in the rate of HF hospitalization. . More powered RCTs are needed to fully investigate the impact of statins on prognosis in patients receiving anthracyclines therapy.
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Figures from the paper
Published by International Journal of Cardiology · CC BY-NC-NDCite This Study
D’Amario et al. (2023) conducted a meta-analysis in Anthracycline-mediated cardiotoxicity in cancer patients (n=808). Statins vs. Placebo was evaluated on Incidence of anthracycline-mediated cardiotoxicity (RR 0.52, 95% CI 0.33-0.83, p=0.01). Statins significantly reduced the incidence of anthracycline-mediated cardiotoxicity compared to placebo (RR 0.52).