Levosimendan compared to dobutamine for decompensated heart failure

May 2 2007

The drug levosimendan did not improve survival for patients with decompensated heart failure when compared with a more widely-used treatment for this condition, dobutamine, according to a study in the May 2 issue of JAMA.

Acute decompensated heart failure (ADHF; severe heart failure characterized by inability of the heart to maintain adequate blood circulation) remains a common cause of hospitalization worldwide, but appropriate treatment is not always clear. Dobutamine improves symptoms but has been associated with an increased risk of death and other cardiovascular events, according to background information in the article. In a previous study, secondary analyses indicated that the drug levosimendan was associated with lower risk of death compared to dobutamine.

Alexandre Mebazaa, M.D., Ph.D., of the Université Paris Diderot and Hospital Lariboisière AP-HP, Paris, and colleagues with the SURVIVE trial (Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support) conducted a study in which the primary purpose of the trial was to assess long-term survival outcomes for 1,327 ADHF patients who received levosimendan or dobutamine. The trial was conducted at 75 centers in 9 countries and patients were randomized between March 2003 and December 2004. Patients received either intravenous levosimendan (n = 664) or intravenous dobutamine (n = 663).

The researchers found that during the 180 days after drug infusion, there were 173 deaths (26 percent) in the levosimendan group and 185 deaths in the dobutamine group (28 percent). There were no statistical differences between treatment groups for most secondary end points (all-cause death at 31 days, number of days alive and out of the hospital, patient global assessment, patient assessment of dyspnea (difficulty breathing) at 24 hours, and cardiovascular death at 180 days). Compared with dobutamine-treated patients, levosimendan-treated patients were less likely to experience cardiac failure and more likely to experience atrial fibrillation, hypokalemia (abnormally low level of potassium in the circulating blood), and headache during the initial 31 days following study drug administration.

"In conclusion, the SURVIVE trial demonstrated no survival difference between levosimendan and dobutamine during long-term follow-up despite evidence for an early reduction of plasma B-type natriuretic peptide level [an amino acid level that correlates with both the severity of symptoms and the prognosis in congestive heart failure] for levosimendan. These findings may be related to the short duration of treatment in the trial, a selective effect of levosimendan in specific subgroups, or the lack of a true difference between the 2 drugs. Further studies are needed to distinguish between these possibilities," the authors write.