Neurohormonal Therapies May Prevent Cardiotoxicity in Cancer Patients Undergoing Chemotherapy

Research published in JACC CardioOncology suggests that neurohormonal therapies are associated with higher left ventricular ejection fraction (LVEF) during follow-up among cancer patients undergoing chemotherapy.

In this meta-analysis, researchers included 17 randomized clinical trials of comprised of 1,984 adult patients that underwent chemotherapy and neurohormonal therapies such as β-blockers, mineralocorticoid receptor antagonists, or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and assessed efficacy compared to a placebo with follow-up of four or more weeks. The primary outcome was change in left ventricular ejection fraction (LVEF) from baseline to the end of the trial. Other outcomes of interest were measures of LV size, strain, and diastolic function. Pooled estimates for each outcome were reported as standardized mean difference and weighted mean difference between the neurohormonal therapy and placebo groups using random effects models.

According to the results of the study, in pooled analysis, the researchers observed that neurohormonal therapy was associated with significantly higher LVEF upon follow-up juxtaposed to placebo therapy, but with significant heterogeneity in the pooled estimate (I2 = 96%).

Moreover, compared with placebo-treated patients, neurohormonal therapies experienced a 3.96% (95% CI, 2.90 to 5.02) less decline in LVEF estimated by weighted mean difference, but with significant heterogeneity (I2 = 98%). The study also revealed a trend toward lower adverse clinical events with neurohormonal therapy versus place that was not statistical significance (risk ratio: 0.80 95% CI, 0.53 to 1.20; I2 = 71%).

“In this study-level pooled analysis, we observed a significant, but small, benefit of neurohormonal therapies in reducing decline in LV systolic function among patients undergoing chemotherapy,” the researchers wrote in conclusion.

“However, owing to the substantial heterogeneity across the 15 modest-sized studies and potential for publication bias in this updated meta-analysis, our study findings are not sufficient to recommend routine use of RAAS inhibitors or β-blockers as cardioprotective strategies in patients undergoing cardiotoxic chemotherapy (predominantly with anthracycline-based regimens). There is an enduring need for future, adequately powered randomized clinical trials to test the effects of cardioprotective therapies on both cardiovascular and cancer outcomes.”