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.
Eur Heart J
; 37(21): 1671-80, 2016 06 01.
Article
in En
| MEDLINE
| ID: mdl-26903532
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 ß-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 ANDRESULTS:
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 ß-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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tetrazoles
/
Benzimidazoles
/
Biphenyl Compounds
/
Breast Neoplasms
/
Adrenergic beta-Antagonists
/
Angiotensin Receptor Antagonists
/
Heart Failure
/
Metoprolol
Type of study:
Clinical_trials
Limits:
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Eur Heart J
Year:
2016
Document type:
Article
Affiliation country:
Norway