2005 AHA Scientific Sessions: REVIVE II/SURVIVE trials

The calcium sensitizer levosimendan was associated with an improvement in the clinical course of patients compared with placebo when used for the treatment of acute decompensated heart failure (ADHF), but the drug failed to reduce 6-month mortality when compared with dobutamine in a similar set of patients.

The REVIVE II (Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy) trial evaluated levosimendan administered over 24 hours (12 mcg/kg bolus followed by 0.2 mcg/kg/min) plus standard therapy or standard therapy alone in 600 patients with ADHF. The primary end point was a composite of clinical signs and symptoms together with the occurrence of death or worsening heart failure over 5 days.

After 5 days, the likelihood of clinical improvement was 33% greater and the likelihood of clinical deterioration was 29% lower in patients randomized to levosimendan versus placebo (P=.015), reported Milton Packer, MD, professor and director of the Center for Biostatistics, University of Texas Southwestern Medical Center, Dallas, Texas. Also, fewer patients randomized to levosimendan compared with placebo required rescue therapy (15.1% vs 26.2%), and the average hospital stay was shorter among the levosimendan group (7.0 vs 8.9 days; P=.001).

In the SURVIVE (Survival of Patients with Acute Heart Failure in Need of Intravenous Inotropic Support) trial, 1,327 patients with ADHF were randomized to either the same dosing schedule of levosimendan as used in REVIVE II or dobutamine (minimum dosage, 5 mcg/kg/min).

The primary end point was all-cause mortality at 180 days. Although there was a clear trend toward improved survival with levosimendan, the 9.0% reduction in mortality at 180 days in the levosimendan-treated patients failed to achieve statistical significance (26% vs 28%; P=.401), said Alexandre MeBazaa, MD, PhD, principal investigator of SURVIVE, and professor and director, Department of Anesthesia and Critical Care Medicine, Lariboisiere Hospital, Paris, France.

In both studies, levosimendan-treated patients had a higher incidence of atrial fibrillation and hypotension versus the comparator and a lower incidence of cardiac failure.