Followers

Sunday, May 6, 2007

Can Levosimendan Help in Acute Decompensated Heart Failure?


Can Levosimendan Help in Acute Decompensated Heart Failure?

A novel inotropic agent demonstrated no advantage over dobutamine in reducing mortality.

There were hopes that the new drug, levosimendan, would improve survival, because it uses a unique mechanism that makes heart muscle cells more sensitive to the calcium that causes them to contract. However, the study of 1,347 persons with acute decompensated heart failure, done at 75 centers in nine countries between March 2003 and December 2004, found essentially the same death rate for participants who got levosimendan as those who received an established medication, dobutamine, said a report in the May 2 issue of the Journal of the American Medical Association.

Levosimendan vs Dobutamine for Patients With Acute Decompensated Heart Failure

The SURVIVE Randomized Trial

Alexandre Mebazaa, MD, PhD; Markku S. Nieminen, MD, PhD; Milton Packer, MD; Alain Cohen-Solal, MD, PhD; Franz X. Kleber, MD; Stuart J. Pocock, PhD; Roopal Thakkar, MD; Robert J. Padley, MD; Pentti Põder, MD, PhD; Matti Kivikko, MD, PhD; for the SURVIVE Investigators

JAMA. 2007;297:1883-1891.

Context
Because acute decompensated heart failure causes substantial morbidity and mortality, there is a need for agents that at least improve hemodynamics and relieve symptoms without adversely affecting survival.

Objective
To assess the effect of a short-term intravenous infusion of levosimendan or dobutamine on long-term survival.

Design, Setting, and Patients
The Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study was a randomized, double-blind trial comparing the efficacy and safety of intravenous levosimendan or dobutamine in 1327 patients hospitalized with acute decompensated heart failure who required inotropic support. The trial was conducted at 75 centers in 9 countries and patients were randomized between March 2003 and December 2004.
Interventions
Intravenous levosimendan (n = 664) or intravenous dobutamine (n = 663).

Main Outcome Measure
All-cause mortality at 180 days.


Results
All-cause mortality at 180 days occurred in 173 (26%) patients in the levosimendan group and 185 (28%) patients in the dobutamine group (hazard ratio, 0.91; 95% confidence interval, 0.74-1.13; P = .40). The levosimendan group had greater decreases in B-type natriuretic peptide level at 24 hours that persisted through 5 days compared with the dobutamine group (P<.001 for all time points). There were no statistical differences between treatment groups for the other secondary end points (all-cause mortality at 31 days, number of days alive and out of the hospital, patient global assessment, patient assessment of dyspnea at 24 hours, and cardiovascular mortality at 180 days). There was a higher incidence of cardiac failure in the dobutamine group. There were higher incidences of atrial fibrillation, hypokalemia, and headache in the levosimendan group.

Conclusion
Despite an initial reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group compared with patients in the dobutamine group, levosimendan did not significantly reduce all-cause mortality at 180 days or affect any secondary clinical outcomes.

Link:

No comments: