Effects of renin-angiotensin system inhibitors in cancer patients: a systematic review and meta-analysis of randomized controlled trials.

Cardiotoxicity is a growing concern in cancer patients receiving chemotherapy. Renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), are widely used for cardiovascular protection, but their role in cancer care remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of RAS inhibitors on cardiotoxicity, dyspnea, and quality of life (QOL) in patients with malignancies. A comprehensive literature search was performed using PubMed, Embase, Web of Science, and the Cochrane Library, from which 15 eligible RCTs were identified. These trials compared RAS inhibitor users and non-users. Group differences were analyzed using mean differences (MDs) or odds ratios (ORs), with heterogeneity assessed by the I² statistic. Pooled results suggested a possible association between RAS inhibitor use and higher left ventricular ejection fraction (LVEF) compared to controls (MD 4.42%, 95% CI -0.02 to 8.85; I² = 96%). Subgroup analysis revealed significant benefit in patients receiving HER2-targeted therapy and those undergoing non-specific chemotherapy, while no advantage was seen in patients treated with anthracyclines and HER2 blockade. RAS inhibitors showed limited benefit in anthracycline regimens. No significant reduction in cardiotoxicity was observed (OR 0.66, 95% CI 0.19-2.30). Additionally, two trials evaluating ACE inhibitors with beta-blockers demonstrated additive effects in preventing LVEF decline in high-risk populations. One trial also reported improved dyspnea with ACE inhibitors in lung cancer. RAS inhibitors may help preserve cardiac function in cancer patients, but current evidence is inconclusive. Confirmation through large-scale RCTs is warranted.