Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy - PRADA

May 16, 2021
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
University of Oslo, The Extra Foundation for Health and Rehabilitation, The Norwegian Cancer Society, and Akershus University Hospital.
Date Presented:
05/16/2021
Date Published:
05/16/2021
Date Updated:
05/16/2021
Original Posted Date:
02/29/2016
References

Contribution To Literature:

The PRADA trial showed that candesartan, but not metoprolol was effective at preserving LVEF among women undergoing chemotherapy for breast cancer.

Description:

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.

Study Design

  • Randomized
  • Parallel
  • Factorial
  • Placebo

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 with diabetes: <3%
  • Mean left ventricular ejection fraction (LVEF): 62%

Inclusion criteria:

  • 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%

Exclusion criteria:

  • 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

Principal Findings:

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.

Long-term outcomes (median 23 months):

  • Change in LVEF (%) from baseline to follow-up: -1.8 in the no candesartan group, -1.7 in the candesartan group (p = 0.91), -1.9 in the no metoprolol group, -1.6 in the metoprolol group (p = 0.73)
  • Change in peak global longitudinal strain (%) from baseline to follow-up: 1.0 in the no candesartan group, 0.2 in the candesartan group (p = 0.046), 0.8 in the no metoprolol group, 0.4 in the metoprolol group (p = 0.34)
  • Change in end-diastolic volume (cc) from baseline to follow-up: 2 in the no candesartan group, -5 in the candesartan group (p = 0.021), -1 in the no metoprolol group, -2 in the metoprolol group (p = 0.78)

Interpretation:

Among women with breast cancer undergoing anthracycline chemotherapy, candesartan was effective at preserving LVEF. Metoprolol succinate was not effective at preserving LVEF. However, during long-term follow-up, candesartan was no longer associated with a preservation in LVEF. Candesartan was associated with modest improvements in LV end-diastolic volume and global longitudinal strain. Unselected use of these medications does not appear warranted as a cardioprotective strategy among women undergoing treatment for breast cancer.

References:

Omland T, Heck S, Mecinaj A, et al. Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Long-Term Follow-Up of a 2 x 2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol. Circulation 2021;May 16:[Epub ahead of print].

Presented by Dr. Siri Lagethon Heck at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 16, 2021.

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;37:1671-80.

Presented by Dr. Geeta Gulati at the American Heart Association Scientific Sessions, Orlando, FL, November 11, 2015.

Keywords: ACC21, ACC Annual Scientific Session, Adrenergic beta-Antagonists, Anthracyclines, Antibodies, Monoclonal, Humanized, Benzimidazoles, Breast Neoplasms, Chemotherapy, Adjuvant, Heart Failure, Metoprolol, Primary Prevention, Radiation, Receptors, Angiotensin, Stroke Volume, AHA Annual Scientific Sessions


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