Journal
EUROPEAN HEART JOURNAL
Volume 37, Issue 21, Pages 1671-1680Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehw022
Keywords
Angiotensin antagonist; beta-Blocker; Breast cancer; Cardiomyopathy; Imaging; Biomarkers
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Funding
- University of Oslo
- Extra Foundation for Health and Rehabilitation
- Norwegian Cancer Society
- Akershus University Hospital
- Abbott Diagnostics
- AstraZeneca
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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 beta-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 x 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 b-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 20.4, 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.
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