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Eur Heart J. 2016 Jun 1;37(21):1671-80. doi: 10.1093/eurheartj/ehw022. Epub 2016 Feb 21.

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.

Author information

1
Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway.
2
Department of Oncology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
3
Department of Cardiology, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, Ullevål, Oslo, Norway.
4
Department of Cardiology, Charité Campus Buch, University Medicine Berlin, Berlin, Germany HELIOS Clinics Berlin-Buch, Berlin, Germany.
5
Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
6
Department of Breast and Endocrine Surgery, Division of Surgery, Akershus University Hospital, Lørenskog, Norway.
7
Department of Cardiology, Charité Campus Buch, University Medicine Berlin, Berlin, Germany.
8
Department of Oncology, Division of Cancer Medicine, Surgery & Transplantation, Oslo University Hospital-Norwegian Radium Hospital, Oslo, Norway.
9
Intervention Centre, Oslo University Hospital, Oslo, Norway.
10
Institute of Clinical Medicine, University of Oslo, Oslo, Norway Section for Medical Biochemistry, Division for Diagnostics and Technology, Akershus University Hospital, Lørenskog, Norway.
11
Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway torbjorn.omland@medisin.uio.no.

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.

KEYWORDS:

Angiotensin antagonist; Biomarkers; Breast cancer; Cardiomyopathy; Imaging; β-Blocker

PMID:
26903532
PMCID:
PMC4887703
DOI:
10.1093/eurheartj/ehw022
[Indexed for MEDLINE]
Free PMC Article

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