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Post-chemotherapy neurohormonal therapies may improve ejection fraction
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Neurohormonal therapies for the prevention of cardiotoxicity in patients who received chemotherapy conferred improvements in left ventricular ejection fraction as well as left ventricular strain, but benefits were minor and may be within inter-test variability of measurement, researchers reported.
According to findings published in the inaugural issue of JACC: CardioOncology, a meta-analysis of randomized clinical trials assessing beta-blockers, mineralocorticoid receptor antagonists and ACE inhibitors/angiotensin receptor blockers for the prevention of cardiotoxicity found that patients treated with neurohormonal therapies experienced a 3.96% (95% CI, 2.9-5.02) less decline in LVEF compared with placebo, but there was significant heterogeneity among the results (I2 = 98%).
In addition, researchers observed a nonsignificant trend of fewer adverse clinical events in the neurohormonal therapy group (RR = 0.8; 95% CI, 0.53-1.2; I2 = 71%).
LV peak systolic longitudinal strain was better in the neurohormonal therapy group than the placebo group (standardized mean difference, –0.43; 95% CI: –0.69 to –0.16; I2 = 25.8%), according to the researchers.
Small benefit
“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,” Muthiah Vaduganathan, MD, MPH, a fellow in cardiovascular medicine at Brigham and Women’s Hospital Heart and Vascular Center, and colleagues wrote. “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 renin-angiotensin-aldosterone system inhibitors or beta-blockers as cardioprotective strategies in patients undergoing cardiotoxic chemotherapy.”
In other findings, researchers found no significant difference in LV end-systolic dimension (standardized mean difference, –0.4; 95% CI, –0.9 to 0.1), LV end-diastolic dimension (standardized mean difference, –0.32; 95% CI, –0.71 to 0.007) and measures of diastolic function (E/e’ standardized mean difference, –0.18; 95% CI, –0.7 to 0.35 and E/A standardized mean difference, 0.18; 95% CI, –0.07 to 0.42).
Analyzing data from 15 randomized trials of 1,984 adult patients who underwent chemotherapy and neurohormonal therapies compared with placebo with follow up of 4 or more weeks, the researchers sought to determine the effects of these treatments on outcomes in cardiotoxicity. The primary outcomes were change in LVEF from baseline to the end of the trial and the secondary outcomes included LV size, strain and diastolic function.
“Although our study does suggest a potential role of cardioprotective therapy, including with use of RAAS inhibitors and beta blockers, the degree of heterogeneity does limit the interpretability of pooled effect estimates,” the authors wrote.
Knowledge gaps remain
In a related editorial, Guilherme H. Oliveira, MD, MBA, professor of medicine at Case Western Reserve School of Medicine, Cleveland, OH, wrote that many knowledge gaps remain in this area.
“Although not able to provide definitive recommendations regarding the role of neurohormonal agents to prevent cardiotoxicity, this meta-analysis indeed educates the cardio-oncology community,” Oliveira wrote. “It highlights the amount of work still to be done. It sheds light on the gaps of knowledge that afflict the field, even over a decade since its inception. It alerts to the fact that, in cardio-oncology, practice patterns have outpaced scientific evidence and guidelines are ahead of their time; in fact, the cart may be ahead of the horses. This work offers a sobering appraisal of where we stand and where we need to go.” – by Scott Buzby
Disclosures: Vaduganathan reports he received the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst; serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG and Boehringer Ingelheim; and participates on clinical endpoint committees for studies sponsored by Novartis and the NIH. Please see the study for the other authors’ relevant financial disclosures. Oliveira reports no relevant financial disclosures.
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