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PRADA: Candesartan prevents LVEF decline in women treated for breast cancer
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ORLANDO, Fla. — In women treated for early breast cancer, the angiotensin receptor blocker candesartan protected against a decline in left ventricular ejection fraction, but the beta-blocker metoprolol did not, researchers reported here.
Geeta Gulati, MD, from Akershus University Hospital, Lørenskog, Norway, and colleagues examined whether cardiotoxicity in women treated for breast cancer with anthracyclines with or without trastuzumab could be prevented by candesartan or metoprolol, both of which are used in patients with HF.
Geeta Gulati
In PRADA, a 2x2 factorial study, Gulati and colleagues randomly assigned 120 women with early breast cancer and without CVD to one of four interventions: candesartan 8 mg/day to 32 mg/day plus metoprolol 25 mg/day to 100 mg/day; candesartan plus placebo; metoprolol plus placebo; or two doses of placebo. Combined, 60 women received candesartan with or without metoprolol and 58 women received metoprolol with or without candesartan.
The study is the largest conducted of an intervention to prevent decline in cardiac function in patients treated for breast cancer, Gulati said at the American Heart Association Scientific Sessions.
During the intervention, the patients underwent chemotherapy with anthracycline and/or taxanes with those who were HER2-positive also receiving trastuzumab (Herceptin, Genentech); some also received radiation, Gulati said.
The primary outcome was change in LVEF as assessed by cardiac MRI from baseline to the end of treatment. Follow-up ranged from 10 weeks to 61 weeks.
“We used cardiac MRI because that is the most sensitive method to evaluate cardiac function,” Gulati said. “It has high accuracy and low variability.”
Compared with placebo, candesartan was associated with a reduced decline in LVEF, Gulati said. This was true in the intention-to-treat analysis (decline for placebo, 2.6 percentage points; 95% CI, 1.5-3.8; decline for candesartan, 0.8 percentage points; 95% CI, ˗0.4 to 1.9; P for between-group difference = .026) and for the per-protocol analysis (decline for placebo, 2.6 percentage points; 95% CI, 1.4-3.8; decline for candesartan, 0.6 percentage points; 95% CI, ˗0.6 to 1.8; P for between-group difference = .021).
Gulati and colleagues found no effect of metoprolol on change in LVEF, and no evidence of an interaction between assignment to candesartan and assignment to metoprolol.
Limitations include that patients were not followed for longer than the end of their treatment, so long-term effects are not known, and that the patients were at low CV risk, Gulati said.
“In patients treated for early breast cancer, candesartan provided protection against decline in cardiac function,” she said. “We did not see any such effect in the metoprolol group.” – by Erik Swain
Reference:
Gulati G, et al. Late-Breaking Clinical Trials 4. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
Disclosure: The study was sponsored in part by Abbott and AstraZeneca. Gulati reports no relevant financial disclosures.
Perspective
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Mary Norine Walsh, MD, FACC
In the field of cardio-oncology, there is a big emphasis on seeing what we can do to protect people who are receiving cardiotoxic agents. This is an important study demonstrating that the angiotensin receptor blocker was protective when the beta-blocker was not. That will inform our care of these patients going forward.
We are very early in the data, so there is no uniform way that patients are being treated. In the HF/cardiology community, we are just embarking now on seeing all of the oncology patients before they ever receive their treatments to assess their CV risks. This study in particular will help the effort of cardiologists who are trying to engage oncologists in team-based care. There is not a whole lot of guideline work in this area yet, but it’s coming. There is a lot of work going on in certain centers, and it’s expanding to everyday CV practice in the United States.
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