ACE inhibitors, beta blockers may protect against anthracycline-associated cardiotoxicity
medwireNews: The results of two independent trials suggest a role for the prophylactic use of angiotensin converting enzyme (ACE) inhibitors or beta blockers in patients receiving an anthracycline-based regimen for HER2-positive or HER2-negative breast cancer.
Both sets of findings were reported at the American College of Cardiology's 67th Annual Scientific Session in Orlando, Florida, USA.
The presenter of the first trial explained that their aim was to assess the effects of the ACE inhibitor lisinopril and the beta blocker carvedilol in patients initiating adjuvant trastuzumab for localized, HER2-positive disease as cardiac side effects are common with the HER2 inhibitor.
They found that, in the overall cohort, cardiotoxicity-free survival did not differ significantly between the 149 participants who were randomly assigned to receive lisinopril, the 149 who received carvedilol phosphate extended-release, and the 143 given placebo. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) of at least 10% from baseline or a decline of at least 5% to a value below 50%, in both cases with or without heart failure.
But when the researchers stratified the participants by prior receipt of anthracyclines, administration of lisinopril or carvedilol was associated with significantly improved cardiotoxicity-free survival relative to placebo, with corresponding hazard ratios of 0.53 and 0.49.
No such improvement was observed with either the ACE inhibitor or the beta blocker in the subgroup of patients who had not received anthracyclines.
Maya Guglin, from the University of Kentucky in Lexington, USA, told the press that “[t]his data is 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.”
The second trial, which was simultaneously published in the Journal of the American College of Cardiology, enrolled 192 women with HER2-negative breast cancer who were due to begin neoadjuvant or adjuvant anthracycline-based therapy and randomly assigned them to receive carvedilol or placebo.
In a similar vein to the Guglin et al study, the CECCY (Carvedilol Effect in Preventing Chemotherapy Induced CardiotoxicitY) trial also did not meet its primary endpoint, which in this case was a reduction in the proportion of patients who experienced a 10% or greater decline in LVEF from baseline to the cessation of chemotherapy at 6 months. The rates were comparable for the carvedilol and placebo groups, at 14.5% and 13.5%, respectively.
But Monica Avila (Heart Institute do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil) reported that in carvedilol-treated patients, increases in troponin I levels seen across both treatment groups were significantly attenuated, and the carvedilol group had a significantly lower proportion of patients with troponin I levels above 0.04 ng/mL, at 26.0% versus 41.6% in the placebo arm.
Carvedilol treatment was also associated with a trend towards a lower incidence of diastolic dysfunction than placebo.
Taken together, these findings suggest that “the use of carvedilol might offer a preventive strategy for early onset cardiotoxicity to reduce cardiac injury and the LV remodeling process, but [it] has no impact on cardiac function,” Avila and co-authors write.
They add: “[A] longer follow-up will be helpful to evaluate the efficacy of carvedilol in late prevention of cardiotoxicity.”
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