AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Decomposing the Effects of Pharmacological Cardioprotection, Lifestyle Interventions, Cardiac Monitoring Frequency, and Risk Stratification Tools in Preventing Chemotherapy-Induced Cardiotoxicity: A Component Network Meta-Analysis
By Andanappa A, Keswani K, Muzaffer R et al.
Background: Current cardio-oncology guidelines recommend multimodal strategies to prevent chemotherapy-induced cardiotoxicity (CTRCD), yet the independent and synergistic contributions of pharmacological agents, lifestyle interventions, monitoring protocols, and risk stratification remain poorly quantified. Traditional pairwise meta-analyses cannot disentangle these co-administered components, limiting evidence-based optimization of cardioprotective bundles. Component network meta-analysis (CNMA) offers a novel framework to decompose complex interventions into constituent elements. Methods: We conducted a CNMA using additive weighted least squares modeling to decompose eight intervention components across 17 randomized controlled trials enrolling 1,933 patients receiving anthracycline-based and/or HER2-targeted chemotherapy regimens. Components included beta-blockers, ACE inhibitors/angiotensin receptor blockers (ACEi/ARB), statins, dexrazoxane, dietary interventions, structured exercise programs, serial monitoring (echocardiography plus biomarkers), and risk stratification-guided therapy. Primary endpoints were left ventricular ejection fraction (LVEF) mean difference from baseline and cancer therapeutics-related cardiac dysfunction (CTRCD) odds ratios. Interaction analyses evaluated pharmacological-exercise synergy. Results: For LVEF preservation, statins demonstrated robust independent effects (mean difference +2.1%, 95% CI 0.1-4.0, p=0.035), followed by dexrazoxane (+2.6%, 95% CI –0.6 to 5.6, p=0.107), dietary intervention (+2.9%, 95% CI –0.2 to 6.1, p=0.070), beta-blockers (+2.0%, 95% CI 1.0-2.9, p<0.001), and ACEi/ARB (+1.3%, 95% CI 0.3-2.2, p=0.011). Exercise programs alone showed no significant effect (–0.2%, 95% CI –1.7 to 1.3, p=0.814), nor did risk stratification-guided therapy (–0.4%, 95% CI –2.3 to 1.4, p=0.654). Serial monitoring trended toward benefit (+1.3%, 95% CI –0.4 to 2.9, p=0.126). For CTRCD prevention, beta-blockers (OR 0.59, 95% CI 0.41-0.86, p=0.005) and ACEi/ARB (OR 0.66, 95% CI 0.46-0.96, p=0.030) achieved statistical significance, with trends for statins (OR 0.41, 95% CI 0.16-1.03, p=0.057) and serial monitoring (OR 0.44, 95% CI 0.19-1.03, p=0.058). Critically, pharmacological cardioprotection combined with exercise demonstrated synergistic interaction (combined LVEF mean difference +5.8% vs +2.4% pharmacological-only; synergistic interaction term Δ=+2.5%). Conclusions: Beta-blockers and ACEi/ARB constitute the minimum effective pharmacological bundle for CTRCD prevention, with statins warranting guideline consideration given robust LVEF and CTRCD effect estimates. Exercise amplifies pharmacological cardioprotection through synergistic mechanisms, supporting integrated cardio-oncology rehabilitation programs rather than isolated interventions.