Table 3.

Primary cardiotoxicity prevention trials in patients with breast cancer [61]

Trial (N)	Intervention	Primary outcome	Benefit (yes/no)
PRADA[63] (N = 130, all anthracycline, 22% trastuzumab)	1:1:1:1, metoprolol, candesartan, metoprolol and candesartan, or placebo	Changes in LVEF by CMR at 10 to 64 weeks	Yes, absolute LVEF change: 2.6% in placebo, 0.8% in candesartan (p = 0.026)
Guglin et al. [64] (N = 468, all trastuzumab, 40% doxorubicin)	1:1:1 carvedilol, lisinopril, or placebo	LVEF > 10% or LVEF decline > 5% with absolute LVEF < 50%	Yes, > 10% LVEF decline in subset with prior anthracycline exposure: 47% placebo, 31% carvedilol, 37% lisinopril (p = 0.009)
Boekhout et al. [65] (N = 206, all epirubicin with trastuzumab)	1:1 candesartan or placebo	LVEF decline of > 15% or a decrease below the absolute value of 45%	No, LVEF decline: 19% in candesartan, 16% in placebo (p = 0.58)
MANTICORE[66] (N = 94, all trastuzumab, 12–33% anthracycline)	1:1:1 bisoprolol, perindopril, or placebo	Changes in LVEDVI by CMR at 1 year	Yes, Small reduction in LVEF decline with bisoprolol compared with perindopril and placebo (-1% vs. -3% vs. -5%, p = 0.001)

Abbreviations: CMR, cardiac magnetic resonance imaging; LVEDVI, left ventricular end-diastolic volume index; LVEF, left ventricular ejection fraction; MANTICORE, Multidisciplinary Approach to Novel Therapies in Cardio-oncology Research; PRADA, Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy