Table 2.
Summary of trials investigating inotropic agents in advanced heart failure
| Drug | Classification/mechanism of action | Trials | Summary of results |
|---|---|---|---|
| Dobutamine 79 | Calcitrope/β‐adrenergic receptor agonist | FIRST (post hoc analysis) | Increased mortality, worsened HF, myocardial infarction, and cardiac arrest with dobutamine. |
| Milrinone 81 , 82 | Calcitrope/phosphodiesterase‐3 inhibitor | PROMISE; OPTIME‐CHF | Higher incidence of hypotension, arrhythmia, and mortality with milrinone vs. placebo. |
| Enoximone 72 , 83 | Calcitrope/phosphodiesterase‐3 inhibitor | Enoximone Multicenter Trial Group; ESSENTIAL trials | No difference in mortality with enoximone vs. placebo. |
| Levosimendan 84 , 85 , 86 , 87 , 88 | Calcitrope/phosphodiesterase‐3 inhibitor and additive properties | LIDO; REVIVE; SURVIVE; PERSIST; LION‐HEART | Improved haemodynamics, increased symptomatic relief, lower natriuretic peptide levels, and lower HF hospitalizations with levosimendan vs. dobutamine and placebo; no improvement in survival with levosimendan vs. placebo. |
| Omecamtiv mecarbil 50 , 99 , 100 , 101 | Myotrope/direct myosin activator | COSMIC‐HF; GALACTIC‐HF | Increased cardiac output, positive cardiac remodelling, and reduced composite endpoint of CV mortality or HF events with omecamtiv mecarbil vs. placebo (greater benefit in those with lower LVEF and severe HF). |
COSMIC‐HF, Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure; CV, cardiovascular; ESSENTIAL, Studies of Oral Enoximone Therapy in Advanced HF; FIRST, Flolan International Randomized Survival Trial; GALACTIC‐HF, Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure; HF, heart failure; LIDO, Levosimendan Infusion versus DObutamine; LION‐HEART, Intermittent Intravenous Levosimendan in Ambulatory Advanced Chronic Heart Failure Patients; LVEF, left ventricular ejection fraction; OPTIME‐CHF, Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure; PERSIST, Effects of Peroral Levosimendan in the Prevention of Further Hospitalisations in Patients with Chronic Heart Failure; PROMISE, Prospective Randomized Milrinone Survival Evaluation; REVIVE (I, II), Randomized EValuation of Intravenous LeVosimendan Efficacy; SURVIVE, Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support.