Key result
Concomitant treatment with candesartan during anthracycline therapy reduced left ventricular total cellular volume (-3.5 mL, 95% CI -4.7 to -2.2) compared to no candesartan (between group difference P=0.003).
Why the study?
Do candesartan and metoprolol prevent anthracycline-induced changes in myocardial tissue composition in women with early breast cancer?
RCT (n=69)
Double-blind
2x2 factorial
Do candesartan and metoprolol prevent anthracycline-induced changes in myocardial tissue composition in women with early breast cancer?
Effect estimate: Mean change -3.5 mL (95% CI -4.7, -2.2)
p-value: p=0.003
Anthracycline therapy causes a dose-dependent increase in myocardial extracellular volume, and concomitant candesartan reduces left ventricular total cellular volume.
Candesartan reduces myocardial cellular volume during anthracycline therapy; extends RCT evidence on tissue-level cardioprotection in breast cancer.
Aims: Anthracycline treatment may cause myocyte loss and expansion of the myocardial extracellular volume (ECV) fraction by oedema and fibrosis. We tested the hypotheses that adjuvant treatment for early breast cancer with the anthracycline epirubicin is dose dependently associated with increased ECV fraction and total ECV, as well as reduced total myocardial cellular volume, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade. Methods and results: PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) was a 2 × 2 factorial, placebo-controlled, double-blinded trial of candesartan and metoprolol. Sixty-nine women had valid ECV measurements. ECV fraction, total ECV, and total cellular volume were measured by cardiovascular magnetic resonance before and at the completion of anthracycline therapy. ECV fraction increased from 27.5 ± 2.7% to 28.6 ± 2.9% (P = 0.002). A cumulative doxorubicin equivalent dose of 268 mg/m2 was associated with greater increase in ECV fraction than doses <268 mg/m2 (mean change 3.4% [95% confidence interval (CI) 1.2, 5.5] vs. 0.7% [95% CI 0.0, 1.5], P = 0.006), as well as greater increase in total ECV (1.9 mL [95% CI 0.4, 3.5] vs. 0.1 mL [95% CI -0.6, 0.8], P = 0.04). In patients receiving candesartan, total cellular volume decreased (-3.5 mL [95% CI - 4.7, -2.2], P < 0.001) while in patients not receiving candesartan, it remained unchanged (P = 0.45; between group difference P = 0.003). Conclusions: Anthracycline therapy is associated with dose-dependent increase in ECV fraction and total ECV. Concomitant treatment with candesartan reduces left ventricular total cellular volume.
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Heck et al. (2017) conducted an RCT in Early breast cancer (n=69). Candesartan and metoprolol vs. Placebo was evaluated on Total cellular volume (Mean change -3.5 mL, 95% CI -4.7, -2.2, p=0.003). Concomitant treatment with candesartan during anthracycline therapy reduced left ventricular total cellular volume (-3.5 mL, 95% CI -4.7 to -2.2) compared to no candesartan (between group difference P=0.003).
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