Women with breast cancer who recieved the angiotensin-receptor blocker candesartan had no reduction in the heart’s pumping function following adjuvant cancer therapy, whereas the betablocker metoprolol prevented an increase in markers of heart damage. Geeta Gulatis‘s PhD thesis is based on the PRADA study from Akershus University Hospital.

MAIN RESULTS:

1. Candesartan protects against early decline in systolic heart function following adjuvant anthracycline-containing breast cancer therapy
2. Metoprolol prevents an increase in markers of heart damage during breast cancer therapy
3. Neither candesartan nor metoprolol prevents increased cardiac fibrosis following anthracycline therapy.

THESIS DEFENCE:

Thesis: Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy
Candidate: Geeta Gulati
Time: April 25, 2018 at 13:15
Place: Akershus University Hospital: Large Auditorium
Link to university website (in Norwegian)

SUMMARY:

(1) The PRADA study includes 120 otherwise healthy women who were treated for breast cancer between 2011 and 2014. The women were randomized to four groups, that in addition to anthracyclines received either candesartan (a blood pressure drug), metropolol (a betablocker), both drugs or placebo. 

(2) The researchers used cardiac MRI to look at global left ventricular function, and found the systolic function to be reduced after completion of anthracycline therapy. However, those who received candesartan did not have any decline in heart function.

(3) In 69 of the women, Gulati and coworkers also measured the extracellular volume of the hearts, an indication of edema and/or stiffening of the heart (fibrosis). The extracellular volume increased in a dose-dependent manner during the 13 weeks of anthracycline therapy. Neither metoprolol nor candesartan prevented this increase.

(4) The levels of several markers of heart damage increased following adjuvant breast cancer therapy. Larger increases were however not associated with a larger decrease in heart function. Metoprolol protected against the increase in troponins, whereas candesartan did not have any effect.

REFERENCES:

(1) Heck, S. L., Gulati, G., Ree, A. H., Schulz-Menger, J., Gravdehaug, B., Røsjø, H., Steine, K., Bratland, Å., Hoffman, P., Geisler, J., & Omland, T. (2012). Rationale and design of the prevention of cardiac dysfunction during an Adjuvant Breast Cancer Therapy (PRADA) Trial. Cardiology, 123(4), 240-247.

(2) Gulati, G., Heck, S. L., Ree, A. H., Hoffmann, P., Schulz-Menger, J., Fagerland, M. W., Gravdehaug, B., von Knobelsdorff-Brenkenhoff, F., Bratland, Å., Storås, T. H., Hagve, T-A., Røsjø, H., Steine, K., Geisler, J. & Omland, T. (2016). Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2× 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. European heart journal, 37(21), 1671-1680.

(3) Gulati, G., Heck, S. L., Røsjø, H., Ree, A. H., Hoffmann, P., Hagve, T. A., Norseth, J., Gravdehaug, B., Steine, J., Geisler, J., & Omland, T. (2017). Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study. Journal of the American Heart Association, 6(11), e006513.

(4) Heck, S. L., Gulati, G., Hoffmann, P., von Knobelsdorff-Brenkenhoff, F., Storås, T. H., Ree, A. H., Gravdehaug, B., Røsjø, H., Steine, K., Geisler, J., Schulz-Menger, J., & Omland, T. (2017). Effect of candesartan and metoprolol on myocardial tissue composition during anthracycline treatment: the PRADA trial. European Heart Journal-Cardiovascular Imaging.