Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy - PRADA
The goal of the trial was to evaluate treatment with a beta-blocker and/or angiotensin-receptor blocker (ARB) among patients with breast cancer undergoing anthracycline chemotherapy.
Contribution to the Literature: The PRADA trial showed that candesartan, but not metoprolol was effective at preserving left ventricular ejection fraction (LVEF) among women undergoing chemotherapy for breast cancer.
Women with breast cancer undergoing anthracycline chemotherapy with or without trastuzumab and/or radiation were randomized by factorial design to metoprolol succinate (target dose 100 mg daily) versus placebo, and to candesartan (target dose 32 mg daily) versus placebo. The duration of the study medication ranged from 10-61 weeks.
- Candesartan/metoprolol (n = 28)
- Candesartan/placebo (n = 32)
- Metoprolol/placebo (n = 30)
- Placebo/placebo (n = 30)
- Total number of enrollees: 120
- Duration of follow-up: 10-61 weeks
- Mean patient age: 51 years
- Percentage female: 100%
- Percentage diabetics: <3%
- Mean LVEF = 62%
- Women ages 18-70 years with breast cancer undergoing chemotherapy
- Serum creatinine <1.6 mg/dl
- Systolic blood pressure ≥110 and <170 mm Hg
- LVEF ≥50%
- No serious concomitant illness
- Prior malignancy requiring chemotherapy or radiotherapy
- Symptomatic heart failure
- Clinically significant coronary disease, valvular disease, or arrhythmia/conduction delays
- Treatment with angiotensin-converting enzyme inhibitor/ARB or beta-blocker within the last 4 weeks
The primary outcome, decline in LVEF from baseline to end of the study, was -0.8% in the candesartan group versus -2.6% in the placebo group (p = 0.026 for between-group difference). Findings were the same among all tested subgroups. Metoprolol was not associated with a change in LVEF versus placebo. Findings were the same among all tested subgroups as well.
Among women with breast cancer undergoing anthracycline chemotherapy, candesartan was effective at preserving LVEF. Metoprolol succinate was not effective at preserving LVEF.
Gulati G, Heck SL, Ree AH, et al. 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 2016;Feb 21:[Epub ahead of print].
Presented by Dr. Geeta Gulati at the American Heart Association Scientific Sessions, Orlando, FL, November 11, 2015.
Keywords: Adrenergic beta-Antagonists, Anthracyclines, Antibodies, Monoclonal, Humanized, Benzimidazoles, Breast Neoplasms, Chemotherapy, Adjuvant, Heart Failure, Metoprolol, Primary Prevention, Radiation, Receptors, Angiotensin, Stroke Volume, Tetrazoles, AHA Annual Scientific Sessions
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