Reviwer : Dr. Oğuzhan Birdal

Name of the Study : Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA)

Published congress: ACC 2021

Full-text link : https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.054698

Background :
Although developments in cancer treatment prolong life expectancy, the increase in cardiovascular side effects limits the treatment options and reduces the quality of life. Anthracyclines used in adjuvant breast cancer treatment and monoclonal antibodies such as trastuzumab and radiotherapy may have cardiotoxic effects.

Objective :
The PRADA study aimed to investigate the effects of candesartan and metoprolol for the prevention of long-term cardiac dysfunction in patients receiving adjuvant breast cancer treatment.

Methods :
The PRADA study was designed as a randomized, double-blind, placebo-controlled 2X2 factorial study. Female patients aged 18-70 years who were diagnosed with early breast cancer and who received adjuvant therapy containing anthracyclines were included in the study. Patients were divided into candesartan/metoprolol, candesartan/placebo, metoprolol/placebo and placebo groups. 120 randomized patients were included in the intention to treat analysis. The primary endpoint was the change in left ventricular ejection fraction (LVEF) as measured by cardiac magnetic resonance. Secondary endpoints were the changes in left ventricular volumes, echocardiographic peak global longitudinal strain (GLS) values, and cardiac troponin concentrations.

Results :
At a median of 23 months after randomisation, a small decrease in LVEF was observed in all groups, but this decrease was not significantly different between groups (1.7% [95% CI, 0.5 to 2.8] in the candesartan arm; 1.8% [95% CI, 0.6 to 3.0] in the non-candesartan group]; in the metoprolol arm, 1.6% [95% CI, 0.4 to 2.7]; in the non-metoprolol group, 1.9% [95% CI, 0.7 to 3.0]). There was no significant difference between the groups in the changes in troponin-I levels. A significant decrease in left ventricular end-diastolic volume was observed in the candesartan receiving group compared to the group not receiving candesartan (p=0.021) and GLS reduction was more pronounced (p=0.046).

Conclusion :
Anthracycline-containing adjuvant therapy for early breast cancer was associated with a decrease in LVEF during long-term follow-up. The use of candesartan and metoprolol during treatment may not protect against reduction in LVEF.

Interpretation :
During adjuvant breast cancer treatment, the reduction in systolic function is not significant. In addition, since the decrease in LVEF cannot be prevented by neurohormonal blockade, it can be concluded that cardioprotective treatment may not be effective in these patients.