Levosimendan vs Dobutamine for Patients With Acute Decompensated Heart Failure

Abstract

A CUTE DECOMPENSATED HEART failure (ADHF) remains a common cause of hospitalization worldwide but it is not clear how patients admitted for clinical deterioration should be managed. Patients are generally treated with diuretics and vasodilators, while patients with evidence of peripheral hypoperfusion also may receive positive inotropes, usually dobutamine or milrinone. These positive inotropic agents improve hemodynamics and symptoms by increasing intracellular cyclic adenosine monophosphate within the failing heart but have been associated with an increased risk of death and other cardiovascular events. 1,2 Levosimendan is a pharmacological agent that exerts positive inotropic effects by binding to cardiac troponin C in a calcium-dependent manner, sensitizing myofilaments to calcium.3,4 Levosimendan also has vasodilatory proper- 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 PatientsThe 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 (PϽ.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. ConclusionDespite 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 clinicaltrials.gov Identifier: NCT00348504

Loop Diuretic Therapy in Heart Failure: The Need for Solid Evidence on a Fluid Issue

“…Results of recent major clinical trials in ADHF were not encouraging. 1,2 Hence, loop diuretics have remained the mainstay of ADHF treatment.…”

Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure

“…In an updated meta‐analysis comprising six trials, we found no statistically significant difference in short‐term mortality,27, 28, 29, 30, 31, 32 long‐term mortality,27, 30, 31, 33, 34, 35 ischemic events,30, 34 acute kidney injury,31 dysrhythmias,30, 36 or hospital length‐of‐stay37 in patients with cardiogenic shock treated with dobutamine vs. levosimendan (Fig. 3, Fig.…”

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011

“…Among these 59 surrogate endpoint trials that had a subsequent clinical endpoint trial, in 24 cases the clinical endpoint trial results validated the positive surrogate trials, while in 20 the subsequent clinical endpoint trial was negative (Table 3). 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 A negative surrogate endpoint trial was less likely to be followed by a positive outcome trial and we identified only 3 such examples ( P =0.02, Figure 2). …”