Systematic review and network meta-analysis of cardio-protective therapies in cancer patients
V Maharajan, M S Andres, E Doris, A Pons Riverola, C Llamedo, C Yi-Hsuan, P Reehal, P O'Drisceoil, S D Rosen, A Lyon, R Southworth, M S NazirAbstract
Background
Cancer therapy-related cardiac dysfunction (CTRCD) is an important complication of cancer treatment that may lead to interruption of treatment. Anthracyclines and anti-HER2 therapies are highly effective but carry risk of myocardial injury, ranging from subclinical changes to overt heart failure. Clinical trials data evaluating cardioprotective strategies remain heterogeneous and lacking direct comparisons between drug classes. Consequently, the optimal pharmacologic approach to cardioprotection remains uncertain. We performed a systematic review and network meta-analysis (NMA) of randomised trials evaluating pharmacologic strategies for primary prevention of CTRCD.
Methods
MEDLINE and Embase were searched from inception to Feb 2026. We included randomised controlled trials enrolling adults receiving anthracycline- and/or anti-HER2–based chemotherapy that evaluated primary prevention of CTRCD. Interventions included beta-blockers, ACE inhibitors, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRA), statins, angiotensin receptor–neprilysin inhibitors (ARNI), and combination regimens. The primary outcome was incidence of clinically meaningful CTRCD (LVEF <50%). Secondary outcomes were study-defined cardiotoxicity (which have changed in definition over time) and absolute change in LVEF. Where LVEF <50% was not reported, proportions were derived assuming normal distribution of follow-up LVEF values.
Results
Forty-two trials (94 treatment arms) were included. For incident LVEF <50%, MRAs demonstrated the largest effect (OR 0.06, 95% CI 0.01–0.44), followed by dual therapy [beta blocker + ACEi/ARB] (OR 0.26, 0.10–0.66) and ACE inhibitors (OR 0.29, 0.10–0.85). Beta-blockers (OR 0.55, 0.33–0.91) and statins (OR 0.52, 0.29–0.94) were also associated with reduced risk, while ARBs and ARNIs were not significant.Secondary analyses suggested divergence across endpoints. Using contemporary, study-defined cardiotoxicity criteria, statins and ARNIs performed best, whereas ACE inhibitors did not demonstrate consistent benefit. ARBs showed no signal of efficacy across outcomes.
Conclusions
Cardioprotective therapy was associated with reduced CTRCD, with effects varying by drug class and outcome definition. Therapies traditionally targeting neurohormonal pathways were most consistently associated with preservation of LVEF, whereas statins and ARNIs showed greater benefit when broader, study-defined cardiotoxicity criteria were applied. In contrast, ARBs demonstrated no consistent signal of efficacy across analyses. Treatment benefit is sensitive to outcome definition, which may partly explain heterogeneity across trials. These findings may have important clinical implications for the choice of cardioprotective therapies in cancer patients undergoing anthracycline or anti-HER2 based therapy.Table 1Figure 1