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ORLANDO -- An angiotensin II receptor blocker may help to preserve cardiac function in patients receiving treatment for breast cancer, according to results of a small trial reported here.
Compared with placebo and the beta-blocker metoprolol, candesartan (Atacand) protected against decline in left ventricular ejection fraction (LVEF) in low-risk patients receiving potentially cardiotoxic treatment for breast cancer, reported , of Akershus University Hospital in Norway, in a presentation at the American Heart Association meeting.
Although the so-called PRADA trial enrolled just 120 patients, it was described as the largest randomized trial yet performed in the context of cardiac dysfunction in breast cancer treatment.
At the press conference, discussant , of the University of Pennsylvania, described the results for candesartan as "a statistically significant but very modest attenuation of the changes" in the MRI imaging measuring LVEF, on the order of 2%-3%.
This was a 2×2 factorial, double-blind, placebo-controlled study that allowed comparisons among candesartan, metoprolol, and placebo.
Patients treated with metoprolol (versus placebo and versus candesartan) showed no attenuation in LVEF changes in patients after treatment. However, , of the MD Anderson Cancer Center in Houston, did not find this surprising. He told 51˶ that candesartan is approved in Europe (where the study took place) for prevention of progression to heart failure, whereas metoprolol has never been shown to improve or prevent an injury to the heart.
"They're comparing a drug that has been known to prevent a drop in heart function to a drug that has never been shown to prevent that, so you're not really comparing apples to apples, you're comparing apples to a fruit that is inferior," said Durand, who was not involved with the study.
There were no patients who developed heart failure or substantial changes in LVEF during the course of the study.
PRADA recruited breast cancer patients ages 18-70 at a single center, all of whom received epirubicin and 22% of whom received trastuzumab (Herceptin). Importantly, they had a low burden of CV risk factors (1.5% had diabetes and 6.3% had hypertension) and no established cardiovascular disease.
Gulati noted the low-risk population as a potential limitation, along with the fact that follow-up for these patients was confined to the end of their cancer treatment.
Ky commented that additional research was necessary, potentially with a larger sample size and a more extended follow-up time. She added that potentially targeting a population at higher risk of cardiovascular disease might produce a different result.
Durand also said that this has never been looked at as an "epidemic problem" and that the question was if exposing every single patient to these drugs was the best thing to do in clinical practice because of the potential side effects. But overall, he found it a "commendable" study with the important implications for future research.
"It's certainly good news for women who are concerned about how their chemotherapy regimen can affect their heart function, and with further study over a longer period of time, comparing head-to-head with one of the newer third-generation beta-blockers, such as carvedilol (Coreg), can potentially be very important to the practice of cardio-oncology," he concluded.
Disclosures
Gulati disclosed no conflicts of interest. Co-authors reported relationships with Siemens, Modest, Circle, Bayer, SCMR, Modest, AstraZeneca, Abbott Diagnostics, Roche Diagnostics, and Novartis.
Ky disclosed no conflicts of interest.
Primary Source
American Heart Association
Gulati G, et al "Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): Primary results of a randomized, 2x2, factorial, placebo-controlled, double-blind clinical trial" AHA 2015; Abstract 478895.