Lisinopril may prevent trastuzumab–anthracycline-related LVEF decline
medwireNews: Concurrent use of the ACE inhibitor lisinopril could help reduce the risk for left ventricular ejection fraction (LVEF) decline in women receiving trastuzumab and anthracyclines for HER2-positive early breast cancer, suggests US research.
The results of the study involving patients from 127 community-based oncology practices were reported in a poster at the 2021 ASCO Annual Meeting by Pamela Munster, from the University of California San Francisco, and colleagues.
They explained that although trastuzumab is “highly effective” for the treatment of HER2-positive breast cancer, trastuzumab-associated cardiac adverse events “often prompt interruption and discontinuation of treatment,” leading the team to evaluate “the preventive impact of an ACE inhibitor or beta-blockers.”
A total of 424 women who were due to receive neoadjuvant or adjuvant chemotherapy with trastuzumab were randomly assigned in a double-blind fashion to receive lisinopril 10 mg/day, the beta-blocker carvedilol 10 mg/day, or placebo concomitantly with the year-long course of trastuzumab.
The average age of the participants at enrolment was 51.1 years, the majority (86%) were White, and around 43% received an anthracycline-containing regimen.
In all, 11.3% of participants experienced an LVEF reduction of at least 5% and a fall below 50% over a 12-month period. But there was a marked difference in the incidence between patients who did and did not receive anthracyclines, at rates of 21.0% and 4.1%, respectively.
The researchers therefore commented that the impact on LVEF of trastuzumab without anthracyclines is “minimal,” whereas the use of anthracyclines “caused a decrease in LVEF to below 50% in a larger than previously reported number of women.”
However, this risk for LVEF decline among anthracycline-treated patients was significantly reduced with the use of lisinopril relative to placebo, with respective rates of 10.8% and 30.5%.
Carvedilol treatment was also associated with a reduction in the proportion of patients experiencing an LVEF decline to below 50% versus placebo, at 22.8% and 30.5%, but this difference was not statistically significant.
There was also no significant difference between patients who did and did not receive anthracyclines in terms of a decrease in LVEF of at least 10% within the normal range, and this outcome was not affected by either drug.
Munster therefore concluded in a press release that “for those patients in whom anthracyclines are indicated, the trastuzumab-anthracycline induced decline in LVEF could be prevented” with the use of lisinopril.
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