PROACT: Do ACE Inhibitors Help Prevent Cardiotoxicity in Patients Treated For Breast Cancer or Lymphoma?
Patients who took the ACE inhibitor enalapril while undergoing cancer treatment with high-dose anthracycline chemotherapy did not show any difference in troponin T levels at one month after their last chemotherapy dose compared with those who did not take it, according to results from the PROACT study presented during a Late-Breaking Clinical Trial session at ACC.24 in Atlanta.
To determine whether ACE inhibitors could help to prevent anthracycline cardiotoxicity, researchers conducted a multicenter, open-label trial which randomized 111 patients (average age 57 years, 78% women, 98% White British) undergoing treatment for breast cancer (62%) or non-Hodgkin lymphoma (38%) to enalapril or placebo at 13 sites in the U.K. All patients had negative troponin results at the start of the study and were due to receive six cycles (≥300 mg/m2 doxorubicin equivalent) of anthracycline chemotherapy.
During their cancer treatment, participants received anthracyclines at a mean dose of 328mg/m2 doxorubicin equivalent. The mean dose of enalapril was 17.7 mg.
Results of the PROACT trial found there was no significant between-group difference in the primary endpoint of the proportion of patients who experienced a troponin T release, which occurred in 77.8% of the enalapril group and 83.3% of the standard of care group (adjusted odds ratio, 0.65; p=0.405). Additionally, there was no significant difference between groups in terms of troponin I. However, the researchers noted that the proportion of patients testing positive for troponin I (47% of the enalapril group and 45% of the standard of care group) was substantially lower in both groups compared with the proportion testing positive for troponin T.
Outcomes were similar in the two groups for left ventricular ejection fraction, with 2% having a >10% reduction to <50%, and left ventricle global longitudinal strain, with 21% having a >15% relative decrease.
The finding about troponin I "itself has implications because guidelines don't currently differentiate based on type of troponin," said David Austin, MB ChB, the study's lead author. "Both have been shown to be associated with cardiotoxicity in observational studies. I was surprised by the difference, and I think this raises the question of what troponin we should be using."
Based on the findings, researchers said ACE inhibitors are not likely to play a role in future efforts to prevent cardiotoxicity associated with anthracyclines. "The field probably needs to find another [drug] candidate before starting again on another preventative study," said Austin.
Keywords: ACC Annual Scientific Session, ACC24, Cancer, Novel Agents, Cardio-oncology