Prevention of anthracycline-induced cardiotoxicity: a systematic review and meta-analysis

Anthracyclines are extensively used in oncologic patients, in particular for breast cancer and hematological malignancies. Cardiac injury is a potentially dangerous side effect of these drugs. In this systematic review, we analyzed published randomized controlled trials (RCTs) to assess if potential cardioprotective drugs (i.e., renin-angiotensin-aldosterone system [RAAS] blockers and β-blockers) may prevent heart damage by anthracyclines. Studies were identified by electronic search of MEDLINE and EMBASE database until August 2020. The impact of cardioprotective drugs to prevent anthracyclines-induced cardiac injury was expressed as mean difference (MD) or odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I² statistic. Twelve RCTs for a total of 1.035 cancer patients treated with anthracyclines were included. RAAS blockers, β-blockers, and aldosterone antagonists showed a statistically significant benefit in preventing left ventricular ejection fraction (LVEF) reduction (MD 3.57, 95% CI 1.04, 6.09) in 11 studies. A non-statistically significant difference was observed in preventing E/A velocity decrease (MD 0.09, 95% CI 0.00, 0.17; 9 studies), left ventricular end-systolic diameter (LVESD) increase (MD - 0.88, 95% CI, - 2.75,0.99; 6 studies), left ventricular end-diastolic diameter (LVEDD) increase (MD -0.95, 95% CI - 2.67,0.76; 6 studies), and mitral A velocity decrease (MD - 1.42, 95% CI - 3.01,0.17; 4 studies). Heart failure was non-significantly reduced in the cardioprotective arm (OR 0.31, 95% CI 0.06, 1.59; 5 studies). Hypotension was non-significantly increased in the cardioprotective arm (OR 3.91, 95% CI 0.42, 36.46, 3 studies). Cardioprotective drugs reduce anthracycline-induced cardiac damage as assessed by echocardiographic parameters. The clinical relevance of this positive effect is still to be defined.