Lisinopril, carvedilol may prevent chemotherapy-induced cardiotoxicity in some patients
Taking either one of the antihypertensive medications lisinopril or carvedilol when initiating treatment with trastuzumab did not appear to prevent heart function decline in patients with breast cancer, but a subgroup of patients who were also receiving anthracycline-based chemotherapy in addition to trastuzumab benefitted with a significantly reduced risk of heart damage, according to a study.
“Our findings suggest that among women who are only on a standard course of trastuzumab neither carvedilol nor lisinopril seem to make a difference, but for those who had a history of being on anthracycline, these medications can be cardioprotective and should be considered,” said lead author Professor Maya Guglin from the University of Kentucky in Lexington, Kentucky, US.
According to Guglin, the study emerges amidst increasing awareness that certain cancer therapies may contribute to heart problems such as heart failure. “It’s a very difficult scenario, because we don’t want to damage their heart, but at the same time we certainly don’t want to compromise the chances of [a] cure from cancer.”
The prospective, multicentre trial involved 468 patients (mean age 51 years) with HER2-positive breast cancer for whom trastuzumab was clinically indicated. They were randomized to once daily lisinopril (10 mg), carvedilol (10 mg), or placebo, and followed up on heart function by echocardiograms for 2 years. Half of the patients had received or were receiving anthracycline-based chemotherapy. [ACC.18, abstract 405-14]
After 2 years of follow-up, similar risk of cardiotoxicity was observed in the lisinopril, carvedilol, and placebo groups. In addition, neither lisinopril nor carvedilol was better than placebo in preventing disruptions in trastuzumab therapy.
However, among patients who were also receiving anthracyclines on top of trastuzumab, lisinopril (hazard ratio [HR], 0.53) and carvedilol (HR, 0.49) significantly reduced the risk of heart function decline (p<0.05 for both).
Adverse cardiac effects occurred at similar rates across the three groups (proportion of patients, 29 percent for carvedilol, 30 percent for lisinopril, and 32 percent for placebo). The most common adverse events include low blood pressure and dizziness, which were milder with carvedilol than with lisinopril.
“Our study indicates that carvedilol is tolerated better,” said Guglin “But based on our study, if you have breast cancer and your oncologist wants to start you on trastuzumab and you’ve been on an anthracycline, you have a better chance of avoiding decline in cardiac function and taking trastuzumab without damaging your heart if you are pretreated with lisinopril or carvedilol, whichever is tolerated better.”
According to Guglin, clinical guidelines require that women be assessed for ejection fraction, an indication of heart function, before starting trastuzumab—patients with ejection fraction <50 percent are not eligible for the drug. “Because of this initial screening process, we deny [some of] them potentially life-saving medication.”
“Our data affirm that anthracyclines are aggressive agents that can cause damage to the heart muscle on a much greater scale than trastuzumab,” she said.
Nonetheless, Guglin is quick to point out that not all cancer therapies lead to heart problems, and for those associated with such issues, there may be potential ways to minimize the risk of related heart damage.
“Anthracycline-based regimens are more effective for high-risk patients, but the increased cardiotoxicity has limited its use,” said senior co-author Dr Pamela Munster from University of California, San Francisco Medical Center in San Francisco, California, US. “This study is of great importance as it provides the oncologist the option to use an anthracycline in HER2-positive, early-stage breast cancer patients.”