Overview of Randomized Clinical Trials in Acute Heart Failure Syndromes

Acute heart failure syndromes (AHFS) are among the most frequent causes of hospitalizations in the United States and Europe. Despite current therapies, patients with AHFS have high readmission and mortality rates. The randomized, controlled clinical trial is the standard by which contemporary therapies are evaluated, yet this tool of clinical science only recently has been rigorously applied to the development of novel therapies for patients with AHFS. This review briefly discusses some of the challenges presented in designing a clinical trial of therapies for AHFS and to describe some of the recent trials with respect to these issues in established drugs (such as milrinone, dobutamine, nitroglycerin, nitroprusside, and nesiritide) that have been approved by the US Food and Drug Administration (FDA). Recent trials of current investigational agents, such as levosimendan (the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy Versus Placebo in the Short-Term Treatment of Decompensated Heart Failure [REVIVE], the Calcium Sensitizer or Inotrope or None in Low-Output Heart Failure [CASINO] study, and the Survival of Patients with Acute Heart Failure in Need of Intravenous Inotropic Support [SURVIVE] trial), tezosentan (the Randomized Intravenous Tezosentan [RITZ] study and the Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure Studies [VERITAS]), and tolvaptan (the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure [ACTIV-CHF] study), are also discussed.