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

By G. Gulati, S. Heck, A. H. Ree, P. Hoffmann, J. Schulz-Menger, Morten Wang Fagerland, B. Gravdehaug, F. von Knobelsdorff-Brenkenhoff, A. Bratland, T. Storås and 5 more. European Heart Journal, 2016

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Abstract Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function.

Subfields: Cancer Research, Cardiology and Cardiovascular Medicine, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/d09e861d17f903bf088973517de689dabfcd4ba1

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In Cardiology and Cardiovascular Medicine

Citations in the corpus

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines (2016, methodology): “In a recent prospective, placebo-controlled trial in patients with early breast cancer treated with anthracyclines, the ARB candesartan, compared with placebo or beta-blocker therapy, attenuated the decrease in LVEF but had no effect on GLS or cardiac biomarkers.(227)”
2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). (2016, methodology): “In a recent prospective, placebo-controlled trial in patients with early breast cancer treated with anthracyclines, the ARB candesartan, compared with placebo or beta-blocker therapy, attenuated the decrease in LVEF but had no effect on GLS or cardiac biomarkers.(227)”
Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations (2020, methodology): “In another single-centre trial in Norway (n1⁄4 130), patients undergoing anthracycline-based therapy, with or without trastuzumab and radiation, were independently randomly assigned to receive candesartan, metoprolol succinate or matching placebo(s) in a 2 2 factorial design.(68) Candesartan, but no”
Anthracycline Chemotherapy and Cardiotoxicity (2017, methodology): “The recent PRADA trial (Prevention of cardiac dysfunction during adjuvant breast cancer therapy) compared the cardioproctive properties of candesartan and metoprolol in 120 patients with early breast cancer undergoing adjuvant FEC chemotherapy (fluorouracil, epirubin and cyclophosphamide) in a 2 × 2”