Giving an ACE inhibitor to patients having high-dose anthracycline chemotherapy did not protect against cardiac toxicity, a UK trial has found.
Presenting the results of the PROACT study at the American College of Cardiology’s Annual Scientific Session, the researchers said there was no impact of enalapril on biomarkers associated with heart damage.
The team told delegates that the data did not support adding the ACE-inhibitor as a preventive therapy into the standard treatment pathway for this group of patients.
In all, 111 patients undergoing treatment for breast cancer or non-Hodgkin lymphoma were recruited at 13 hospitals across the UK and randomised to receive enalapril or standard care alongside treatment with an average dose of 328mg/m2 doxorubicin-equivalent.
Potential cardiac toxicity was measured by monitoring troponin levels during treatment and one month after the final dose of chemotherapy, as this has been shown to be a biomarker of higher likelihood of changes in heart function, the researchers told the conference.
The patients had an average age of 57 years, and 78% of them were female. All had negative troponin results at the start suggesting no prior heart damage, the team reported.
By the end of the study there was no significant difference between the groups with troponin T release seen in 77.8% of those who received enalapril and 83.3% of those receiving standard of care.
The results also showed no significant difference between groups in terms of troponin I release with 47% testing positive among those receiving enalapril and 45% among those receiving standard of care.
But the researchers expressed surprise that the results of how many patients experienced cardiac damage differed depending on which type of troponin was measured.
Left ventricular ejection fraction and left ventricle global longitudinal strain were also measured with an echocardiogram but similar outcomes between the two groups were found.
The mean dose of enalapril was 17.7mg but more than three-quarters of patients had been titrated to receive 20mg the researchers said.
Study leader Dr David Austin, a consultant cardiologist at the academic cardiovascular unit in James Cook University Hospital in Middlesbrough said they found no evidence that an ACE inhibitor reduced cardiotoxicity during chemotherapy treatment as measured by troponin.
“The conclusion from PROACT is that we would not support the adoption of putting enalapril into a standard care preventative pathway in these patients.”
He added there were implications for guidelines which do not currently differentiate based on type of troponin measured.
“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.”
But it was unlikely that ACE inhibitors would play a role in future efforts to prevent cardiotoxicity associated with anthracyclines, he noted. Patients in the study are being monitored for another year.
“The field probably needs to find another [drug] candidate before starting again on another preventative study,” Dr Austin said.