Levosimendan vs Dobutamine for Patients with acute decompensated heart failure
This review may be edited
Posted By: jon field
Posted Date: 17/5/07
Title: Levosimendan vs Dobutamine for Patients with acute decompensated heart failure
Authors: Alexandre Mebazaa, MD, PhD
Reference: JAMA. 2007;297:1883-1891
Link: Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract: 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, doubleblind 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.
Trial Registration Identifier: NCT00348504
JAMA. 2007;297:1883-1891
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
Randomization was performed by a 2-step procedure (FIGURE 1). First, vials containing study drug were assigned a number using randomly permuted blocks. Second, patients were randomized centrally, using an interactive voice response system, to receive levosimendan or dobutamine at a ratio of 1:1. Randomization was stratified using a biased coin algorithm with previous ADHF and country as factors.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
Yes. An intention to treat analysis was conducted which included all patients enrolled and randomised (664 assigned to Levo and 663 assigned to Dob).
In the levo group 3 were lost to follow up and 30 had intervention discontinued and in the dobutamine group 8 were lost to follow up and 41 had the intervention discontinued. Outcomes for all these patients were included in the ITT analysis.
2b. Were patients analyzed in the groups to which they were randomized?
Yes. Although there seemed to be some patients who received both treatments,[75 (11%) patients in levosimendan group received open-label dobutamine (n=72) or levosimendan (n=3) while 79 (12%) patients in the dobutamine group received open-label dobutamine (n=74) or levosimendan (n=5)] which may dilute the results, patients were only analysed in the groups to which they were randomised.
3. Were patients, health workers, and study personnel blind to treatment?
4. Were the groups similar at the start of the trial?
5. Aside from the experimental intervention, were the groups treated equally?
Unable to say. No mention of IABP or vasoconstrictors use or referral for surgery.
What are the Results?
1. How large was the treatment effect?
No difference in mortality
During the 180 days after study drug infusion, there were 173 deaths (26%) in the levosimendan group and 185 deaths in the dobutamine group (28%) (hazard ratio, 0.91 [95% confidence interval, 0.74-1.13] P=.40; FIGURE 2).
Analysis of all-cause mortality at 31 days and cardiovascular mortality at 180 days also showed no difference between the treatment groups.
2. How precise was the estimate of the treatment effect?
(hazard ratio, 0.91 [95% confidence interval, 0.74-1.13] P=.40;
This trial cannot claim mortality was similar, since at the planned power (85%) it can only rule out a 5% or greater mortality difference with 85% certainty.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
These are not ICU patients. Only 24 pts were ventilated, 271 had SBP<100, vasoconstrictors and IABPs are not mentioned, indeed the inclusion criteria were somewhat broad and non-specific.
"All patients had an ejection fraction of 30% or less" within the previous 12 months and required intravenous inotropic support, as evidenced by an insufficient response to intravenous diuretics and/or vasodilators, and at least 1 of the following at screening: (1) dyspnea at rest or mechanical ventilation for ADHF; (2) oliguria not as a result of hypovolemia; or (3) pulmonary capillary wedge pressure of 18 mm Hg or higher and/or cardiac index of 2.2 L/min per m2 or less." so EF < 30% in the last 12 months and SOB gets you in the study.
2. Were all clinically important outcomes considered?
Mortality was considered but quality of life and physical function may be very important to these patients. Costs could also have been considered.
3. Are the likely treatment benefits worth the potential harms and costs?

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