A Call for Nuance in Cardioprotection With Early Breast Cancer Therapy

For low-risk breast cancer patients getting potentially cardiotoxic treatment, candesartan’s (Atacand) short-term protection of cardiac function faded longer term in the PRADA trial.

Left ventricular ejection fraction (LVEF) declined a similar amount from baseline to 23 months post-randomization for patients given candesartan during adjuvant breast cancer treatment versus those who were not (1.7 vs 1.8 percentage points, P=0.91), reported Siri Heck, MD, PhD, of Akershus University Hospital in Lørenskog, Norway, at the American College of Cardiology (ACC) virtual meeting.

The angiotensin II receptor blocker had previously been shown in the trial at the end of adjuvant therapy to protect against decline in LVEF.

Again, though, as in the main results of the trial, metoprolol given in the other portion of the two-by-two factorial design trial had no impact compared with its control group at 23 months (LVEF decline of 1.6 vs 1.9 percentage points, P=0.73).

The trial enrolled a fairly low-risk group — 120 women; ages 18-70 — being treated for early breast cancer at a single center. All received the anthracycline epirubicin and 23% received trastuzumab (Herceptin) among other adjuvant treatment. Only 1.5% had diabetes and 6.3% had hypertension, while none had established cardiovascular disease.

The extended follow-up analysis, simultaneously published in Circulation, included 98 patients who returned for cardiac MRI.

While there was an early impact of candesartan on troponin, no between-group differences were seen at 2 years.

Candesartan did impact two secondary outcomes, reducing end-diastolic volume by 5 mL compared to the increase of 2 mL in the no-candesartan group (P=0.021) and less decline in global longitudinal strain (0.2 vs 1.0 percentage points, P=0.046).

“This would suggest that candesartan has favorable remodeling effects, but the effect sizes were quite small and the clinical relevance of these changes more than a year after end of therapy is unclear,” Heck cautioned.

The small changes in LVEF seen in the trial limited the potential for impact from cardioprotection and the power the trial had to detect them, Heck noted.

“Routine cardioprotective therapy … seems not to be required for most patients,” she concluded. “It is, of course, good news for many women without high risk to know that the cardiovascular impact is relatively modest in most patients.”

ACC session discussant Bonnie Ky, MD, of the University of Pennsylvania in Philadelphia, agreed that the take-home message was to target cardioprotective therapy according to risk.

Good candidates may include those patients who already have cardiovascular problems, those with diabetes, hypertension, or hyperlipidemia, commented Daniel Lenihan, MD, of Washington University in St. Louis, who was not involved in the trial.

“But if somebody is completely healthy, and they are exercising and there is nothing wrong with their heart and they’re about to get treatment for breast cancer, candesartan is probably not warranted,” he told MedPage Today.

It’s important to know that there is a safe group of patients for potentially cardiotoxic breast cancer treatments, noted ACC press conference discussant Ana Barac, MD, PhD, of Georgetown University in Washington, but the bigger point is awareness of patients with high cardiovascular risk and often abnormal ejection fraction.

“The little elephant in the room here is that oncology practice sometimes mandates what the exclusion criteria are for anthracyclines and trastuzumab,” she said. “They are approved only for normal cardiac function. We all know that in clinical practice we see patients who do not have normal function. Those are the patients at the highest risk. I believe that the next studies your group [Heck] will also take on will include this higher risk [group] of patients.”