PROACT: Enalapril Does Not Mitigate Anthracycline Toxicity in Breast Cancer and NHL

By Leah Kosyakovsky on

Key Points:

  • Anthracycline toxicity is an important cause of cardiomyopathy; it is unclear whether prophylactic treatment with ACE inhibitors could mitigate this risk.
  • In PROACT, enalapril was compared to standard of care in individuals undergoing anthracycline treatment for breast cancer or NHL. The primary endpoint was myocardial injury (defined as cTnT≥14 ng/L). 
  • Enalapril did not result in a significant reduction in anthracycline toxicity as measured by myocardial injury, LVEF, or GLS a month after chemotherapy completion.

While anthracycline toxicity is a well-established cause of new cardiomyopathy, there is very limited evidence whether prophylactic GDMT may prevent toxicity. ACE inhibitors have been hypothesized to be protective against the development of anthracycline toxicity. In a breaking presentation at the 2024 ACC conference today, Dr. David Austin and his team presented their study: “Can we Prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma? (PROACT).”

The PROACT study (NCT03265574) was a multi-center, blinded, randomized controlled trial examining the safety and efficacy of enalapril in the prevention of anthracycline toxicity. Participants were required to receive 6 cycles (ie, high-dose, or ≥ 300mg/m2 doxorubicin equivalent) of anthracycline chemotherapy for either breast cancer or NHL. Key exclusions were baseline myocardial injury, reduced LVEF, or pre-existing RAAS therapy. The primary endpoint was myocardial injury (defined as cTnT≥14 ng/L). Key secondary outcomes included cTnI>26.2 ng/L, LV GLS >15% relative decline from baseline, and LVEF >10% absolute decline from baseline.

A total of 111 patients were 1:1 randomized to either enalapril or standard of care. Enalapril was titrated to 20mg in >75% of patients in the treatment arm, with a mean dose of 17.7mg. The mean age was 58 with 77% women; most patients (62%) had breast cancer, and 3.6% had pre-existing coronary disease. There was no reduction in the primary endpoint of myocardial injury (as measured by cTnT) with enalapril treatment (adjOR 0.65, 95% CI [0.23, 1.78]; p=0.41) up to a month post chemotherapy; interestingly, 81% of all patients developed myocardial injury. In secondary analyses, there was similarly no significant reduction in myocardial injury as measured by cTnI (adjOR 1.10, 95% CI [0.50, 2.38]; p=0.82), LV GLS (adjOR 0.95, 95% CI [0.33, 2.74]; p=0.92), or LVEF (adjOR 4.89, 95% CI [0.40, 674.62]; p=0.24).

When discussing the clinical implications of the study at the ACC conference, Dr. Austin stated: “Adding enalapril to standard care was not superior…in the prevention of cardiotoxicity in patients receiving high-dose anthracycline…chemotherapy.”