Existing agents such as statins and beta-blockers showed cardioprotective properties in select subgroups, but more treatments are needed to protect against heart failure in patients receiving treatment for cancer, according to findings from a systematic review and meta-analysis presented at the European Society of Cardiology (ESC) Cardio-Oncology Congress 2026.
“By pooling together study results, we have confirmed that guideline-recommended heart failure therapies—particularly a combination of RAAS inhibitors plus beta-blockers—protect heart function in patients being treated for cancer. The number of studies with other heart failure therapies was low, highlighting the need for further randomized trials, particularly of newer cardiovascular treatments, to fully understand their place in cardio-oncology,” said principal investigator Wouter Meijers, MD, PhD, a postdoctoral fellow at Erasmus University Medical Center.
Study Methods
“We conducted a meta-analysis of data from published studies to better understand how much different heart failure-recommended therapies prevent cardiac deterioration in patients treated with anticancer drugs,” said presenter Ymke Appels, a PhD candidate in cardio-oncology at the Erasmus University Medical Center in the Netherlands.
The researchers searched EMBASE and PubMed for randomized controlled trials that evaluated heart failure guideline–recommended medical therapy for the prevention of cancer therapy–related cardiac dysfunction in patients with cancer who were treated with any established anticancer therapeutic. The researchers focused on RAAS inhibitors, beta-blockers, mineralocorticoid antagonists, statins, and sodium-glucose cotransporter-2 inhibitors. Two independent reviewers selected the studies, extracted the data, and conducted risk-of-bias assessments.
The primary outcome measure was change in left ventricular ejection fraction (LVEF) with vs without treatment.
Key Findings
The meta-analysis included 36 randomized controlled trials comprising 3,968 patients.
Treatment with RAAS inhibition led to significant improvements in LVEF in patients treated with anthracyclines (weighted mean difference [WMD] = 3.64; 95% confidence interval [CI] = 0.21–7.08) and those treated with anti-HER2 therapies (WMD = 4.15; 95% CI = 2.49–5.81). Significant improvements were not observed in patients treated with anthracyclines and anti-HER2 therapies who received RAAS inhibitors (WMD = 0.08; 95% CI = –1.19 to 1.36). Overall, across all of the related studies, RAAS inhibition improved LVEF function by 2.88% vs placebo or standard of care (P < .001).
Beta-blockers showed similar trends for patients treated with anthracyclines (WMD = 1.05; 95% CI = 0.04–2.06), anti-HER2 therapies (WMD = 4.01; 95% CI = 2.07–5.96), and both (WMD = 0.67; 95% CI = –0.68 to 2.01). Overall, beta-blockers improved LVEF function by 1.20% vs placebo or standard of care (P = .05).
Statins showed LVEF preservation in patients treated with anthracyclines (WMD = 2.54; 95% CI = 1.51–3.56), but limited findings supported claims for the benefits of statins in patients treated with anti-HER2 therapies. Statins improved LVEF function by 2.49% vs controls (P < .001).
Mineralocorticoid antagonists as well as a combination of RAAS inhibitors and beta-blockers showed protective effects for patients who were treated with anthracyclines, but there were few randomized controlled trials to support these findings. Mineralocorticoid antagonists improved LVEF function by 4.68% and the combination of RAAS inhibition and beta-blockers improved LVEF function by 2.98% (P < .001), both compared with placebo or standard of care.
No randomized controlled trial data were available for sodium-glucose cotransporter-2 inhibitor use.
“ESC Guidelines for cardio-oncology recommend using certain treatments in patients with cancer who show signs of cardiac dysfunction, but the evidence for this comes largely from small studies, from expert opinion, and/or by adapting other guidelines such as those on heart failure,” Ms. Appels said.
DISCLOSURES: Funding was provided by ZonMW and the European Research Council. Ms Appels reports no disclosures of interest. Dr. Meijers has received speaker/advisory board fees from Daiichi Sankyo, Nordic Pharma, Astellas, MSD and Novartis.
