Lisinopril and Carvedilol Reduce Cardiotoxicity in HER2+ Breast Cancer

Lisinopril and carvedilol failed to preserve left ventricular ejection fraction (LVEF) in patients with HER2-positive breast cancer treated with trastuzumab (Herceptin), according to a placebo-controlled randomized trial. The agents did, however, show efficacy specifically in those patients previously treated with anthracyclines.

“Herceptin is arguably the most effective treatment for HER2-positive breast cancer,” said Maya Guglin, MD, of the University of Kentucky in Lexington, according to a press release. “These patients are already anxious about their future. We don’t want to avoid this exceptionally effective treatment just because it might cause damage to the heart.”

Previous research has shown that trastuzumab is associated with cardiotoxicity, in the form of decreased LVEF or outright heart failure. Guglin presented results of the new study testing whether an ACE inhibitor or a beta blocker might reduce those effects at the American College of Cardiology’s 67th Annual Scientific Session, held March 10

12 in Orlando.

The study included 468 patients with HER2-positive breast cancer treated with either adjuvant or neoadjuvant trastuzumab. They were randomized to receive either lisinopril, carvedilol phosphate-extended release, or placebo, and they were followed for 2 years.

The primary analysis showed no difference between either of the two study drugs and placebo for the prevention of cardiotoxicity. Also, the number of patients who required a treatment interruption of trastuzumab was no different across the three study arms.

In a subset of patients previously treated with anthracyclines, however, there was a difference. Among only those patients, the cardiac event rate in the placebo group was 47%, compared with 37% with lisinopril and 31% with carvedilol (P < .05 for both compared with placebo). The hazard ratio for cardiac toxicity indicates a large benefit, according to the authors, at 0.49 for carvedilol and 0.53 for lisinopril.

“These data are the crucial first step towards establishing a new standard of care to reduce the risk of cardiotoxicity for patients undergoing treatment for HER2-positive breast cancer,” Guglin said. She noted that a number of questions still remain, including whether doxorubicin and trastuzumab should always be used together, and what level of LVEF should be considered normal even when a decrease is asymptomatic.

“All of these questions require careful consideration, but this part is clear: giving an ACE inhibitor or beta blocker to patients taking doxorubicin and Herceptin for HER2-positive breast cancer will significantly reduce the risk of cardiotoxic side effects,” Guglin said.