Survival of Patients with Acute Heart Failure in Need of Intravenous Inotropic Support - SURVIVE

Nov 16, 2005
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Date Presented:
01/01/2005
Date Published:
01/01/2007
Date Updated:
11/16/2005
Original Posted Date:
11/16/2005
References

Description:

The goal of the trial was to evaluate treatment with levosimendan compared with dobutamine among patients with acute heart failure in need of intravenous inotropic support.

Study Design

Study Design:

Patients Enrolled: 1327
Mean Follow Up: 6 months
Mean Patient Age: Mean age 67 years
Female: 18

Patient Populations:

Hospitalization for acute heart failure, left ventricular ejection fraction ≤30%, clinical need for inotropic therapy after intravenous diuretics and/or vasodilators.

Primary Endpoints:

All-cause mortality at 6 months

Secondary Endpoints:

All-cause mortality at 31 days, BNP at 24 hours, days alive out of hospital, change in patient dyspnea assessment, change in patient global assessment.

Drug/Procedures Used:

Patients were randomized in a double-blind manner to either treatment with levosimendan (12 µg/kg bolus plus 0.1-0.2 µg/kg/min infusion for 24 hours) (n=663) or dobutamine (≥5 µg/kg/min infusion for ≥24 hours) (n=664).

Principal Findings:

Baseline characteristics were similar in both groups, with 88% of patients having a history of heart failure, 86% in New York Heart Association class IV heart failure, and a baseline ejection fraction of 24%. Median BNP was 1178 pg/mL and 1231 pg/mL. Levosimendan infusion duration was 23 hours and dobutamine infusion was 39 hours.

There was no difference in the primary endpoint of all-cause mortality at 180 days (26.1% in levosimendan group and 27.9% in dobutamine group, hazard ratio [HR] 0.91, p=0.40). Likewise, there was no difference at 5 days (4.4% vs 6.0%, HR 0.72, p=NS) or 31 days (11.9% vs 13.7%, HR 0.85, p=NS). BNP at 24 hours was lower in the levosimendan group compared with dobutamine (p<0.001). In the subgroup of patients with history of heart failure, mortality trended lower at 5 days (HR 0.58, 95% CI 0.33-1.01) but was not significantly lower. In a meta-analysis of the LIDO, CASINO and SURVIVE trials, mortality at 6 months was lower in the levosimendan group (relative risk 0.76, p=0.032).

Among the adverse events, atrial fibrillation occurred more often in the levosimendan group (9% vs 6%), while cardiac failure occurred less often in the levosimendan group (12% vs 17%). There was no difference in hypotension (16% vs 14%) or ventricular tachycardia (8% vs 7%).

Interpretation:

Among patients with acute heart failure in need of intravenous inotropic support, treatment with levosimendan was not associated with a reduction in mortality at 6 months compared with dobutamine.

Patients with acute heart failure in need of inotropic support are a particularly higher risk population, with a high mortality rate (27%) in the present study by 6 months. Levosimendan, a novel drug that acts as a calcium sensitizer, has been proposed as an alternative to standard treatment with dobutamine. Earlier trials such as LIDO and CASINO showed lower rates of mortality with levosimendan, although these were small pilot trials. The much larger SURVIVE study did not confirm these mortality findings at either early or late timepoints, although the relative benefit appeared greater early rather than later after the initial infusion.

References:

Mebazaa A, et al. Levosimendan vs Dobutamine for Patients with Acute Decompensated Heart Failure. The SURVIVE Randomized Trial. JAMA. 2007;297:1883-1891.

Presented by Dr. Alexandre Mebazaa at the American Heart Association Scientific Session, Dallas, Texas, November 2005.

Keywords: Phosphodiesterase Inhibitors, Risk, Diuretics, Hypotension, Vasodilator Agents, Pyridazines, Dobutamine, Tachycardia, Ventricular, Heart Failure, Stroke Volume, Hydrazones, Cardiotonic Agents


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