Lisinopril and carvedilol both failed to prevent cardiotoxicity in breast cancer patients treated with only trastuzumab, but both drugs prevented cardiotoxicity in patients who received anthracycline therapy in addition to trastuzumab, according to results of a clinical trial presented by Maya E. Guglin, MD, FACC, on Sunday, March 11 in a Late-Breaking Clinical Trial session at ACC.18 in Orlando, FL.

Researchers were investigating whether the administration of lisinopril or carvedilol decreases cardiotoxicity compared with placebo in patients with breast cancer undergoing treatment with trastuzumab. A total of 468 patients with HER2 positive breast cancer scheduled to receive adjuvant trastuzumab therapy were randomized to lisinopril (10 mg), carvedilol (10 mg Coreg CR) or placebo for two years. Half of the patients were receiving or had received an anthracycline and half had not. The cardiovascular risk profile was similar in both groups and their average age was 58 years. 

The patients had a left ventricular ejection fraction (LVEF) ≥50 percent at study enrollment. The primary endpoint was cardiotoxicity defined as ≥10 percent decrease in LVEF from baseline or an absolute decrease ≥5 percent in LVEF in patients with LVEF <50 percent at study follow-up. Secondary endpoints were interruptions in trastuzumab and treatment effects in anthracycline versus non-anthracycline cohorts.

The occurrence of cardiotoxicity during follow-up was similar in the lisinopril, carvedilol and placebo groups. Treatment interruptions were also similar in the three groups. Carvedilol and lisinopril were effective in preserving LVEF in patients who were treated with an anthracycline. In this cohort, both drugs reduced declines in heart function by half compared with placebo, a statistically significant difference. Adverse cardiac events were similar in the three groups, occurring in 32 percent of patients on placebo, 29 percent on carvedilol and 30 percent on lisinopril. Common adverse events included low blood pressure and dizziness.

"Our study indicates that carvedilol is tolerated better," Guglin said. "But based on our study, if you have breast cancer and your oncologist wants to start you on Herceptin and you've been on an anthracycline, you have a better chance of avoiding decline in cardiac function and taking Herceptin without damaging your heart if you are pretreated with lisinopril or carvedilol, whichever is tolerated better."

Keywords: ACC18, ACC Annual Scientific Session, Heart Failure, Lisinopril, Anthracyclines, Cardiotoxicity, Neoadjuvant Therapy, National Cancer Institute (U.S.), Stroke Volume, Propanolamines, Carbazoles, Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, Breast Neoplasms, Heart Failure, Phosphates

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