Table 3.

Use of key contemporary heart failure therapeutics in prior clinical trials of positive inotropes

Study	Therapy	Year	IHD	Beta‐blocker	ACEi/ARB	ICD	Digoxin	Risk of death
Xamoterol in Severe Heart Failure41	Xamoterol vs. placebo	1990	60%	Excluded	> 80%	Unknown	53%	↑ Risk of all‐cause mortality with xamoterol
PROMISE42	Milrinone vs. placebo	1991	54%	Excluded	Yes, unknown	Unknown	Yes, unknown	28% increase in all‐cause mortality, 34% increase in CV mortality
PICO43	Pimobendan vs. placebo	1996	70%	Excluded	Yes, 100%	Excluded	59%	NS increase in risk of all‐cause mortality
PRIME II44	Ibopamine vs. placebo	1997	59%	Unknown, but low	92%	Unknown	64%	26% increase in all‐cause mortality
VEST45	Vesnarinone vs. placebo	1998	60%	Excluded	90%	Excluded	Unknown	21% increase in all‐cause mortality with vesnarinone
FIRST46	Epoprostenol vs. placebo	1999	67%	Unknown, but low	84%	Unknown	Yes, Unknown	↑ Risk with epoprostenol infusion (trial stopped), ↑ risk in DBA subgroup
OPTIME‐CHF48	Milrinone vs. placebo	2002	51%	22%	82%	Unknown	78%	↔ No difference compared with placebo
REVIVE54	Levosimendan vs. placebo	2004	53%	68%	77%	Unknown	52%	↔ No difference compared with placebo
Enoximone Clinical Trials Program14, 53	Enoximone vs. placebo	2009	52%	83%	98%	21%	69%	↔ No difference compared with placebo
COSMIC‐HF56	Omecamtiv mecarbil vs. placebo	2016		98%	94%	62%	20%	Phase 2 study
PROFILE57	Flosequinan vs. placebo	2017	67%	<4%	Yes, 100%	Unknown	Yes, Unknown	39% increase in all‐cause mortality

ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; CV, cardiovascular; ICD, implantable cardioverter‐defibrillator; IHD, ischaemic heart disease.