Table 1.

Summary of 5 Randomized Controlled Trials Evaluating the Effect of β‐Blockers and Neurohormonal Medications in Preventing Cardiac Dysfunction During Treatment With Trastuzumab, Anthracyclines, or Their Combination

Year, Citation (Trial Name)	Cancer Therapy; Primary End Point	N	Medication	Follow‐Up Period	Results	Conclusion
2006, Cardinale et al7	Anthracycline; LVEF decreased by 10%	114	Enalapril	12 mo	0 vs 43%; P<0.001	Benefit
2016, Gulati8 (PRADA)	Anthracycline with or without trastuzumab; change in LVEF by cMRI	130	Candesartan	10–61 wk	Modest decline in LVEF with candesartan vs placebo (P=0.025)	Mild benefit with candesartan
			Metoprolol	10–61 wk	No change in LVEF with metoprolol vs placebo (P=NS)	No benefit
2016, Boekhout et al9	Trastuzumab; change in LVEF	206	Candesartan	2 mo	Candesartan had higher incidence of cardiac events vs placebo (P=NS)	No benefit, possible harm
2017, Pituskin et al10 (MANTICORE 101‐Breast)	Trastuzumab (25% with anthracyclines); reduce LV remodeling	94	Perindopril	52 wk	Attenuated LVEF decline but did not prevent LV remodeling	Possible benefit
			Bisoprolol	52 wk	Attenuated LVEF decline prevent LV remodeling	Possible benefit
2019, Guglin et al11	Trastuzumab only; LVEF decline and treatment interruptions	468	Lisinopril	1+2 y follow‐up	No difference from placebo	No benefit
			Carvedilol	1+2 y follow‐up	No difference from placebo	No benefit
	Trastuzumab plus anthracyclines; LVEF decline and treatment interruptions		Lisinopril	1+2 y follow‐up	HR: 0.53; P=0.015	Benefit
			Carvedilol	1+2 y follow‐up	HR: 0.49; P=0.009	Benefit

cMRI indicates cardiac magnetic resonance imaging; HR, hazard ratio; LV, left ventricular; LVEF, left ventricular ejection fraction; MANTICORE‐101 Breast, Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research; NS, not significant; PRADA, Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy. 1+2 y;1 year and 2 years of follow up.