Levosimendan Infusion Provides Prolonged Efficacy and Safety in Patients With Acute Heart Failure: Presented at HF2008

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Title: Levosimendan Infusion Provides Prolonged Efficacy and Safety in Patients With Acute Heart Failure: Presented at HF2008
URL: http://www.pslgroup.com/dg/223AC6.htm
Doctor's Guide
June 16, 2008

By Chris Berrie

MILAN, Italy -- June 16, 2008 -- Prolonged levosimendan infusion without a loading dose can significantly decrease brain natriuretic peptide (BNP) levels and filtered QRS duration (fQRSd) for an acceptable clinical and neurohormonal response and a low arrhythmogenic profile in patients with acute decompensated heart failure (ADHF).

Georgios Aidonidis, MD, Department of Cardiology, West German Heart Centre, Medical School, University of Duisberg-Essen, Essen, Germany, presented this study here on June 15 at the Heart Failure 2008 (HF2008) Congress.

Levosimendan was previously shown to have an inotropic effect in patients with ADHF, Dr. Aidonidis explained during a presentation on June 15. "The concept of this study was to use this inotrope without the loading dose, which often provokes hypotension," he added.

His team therefore investigated the efficacy and safety of levosimendan over more than 24 hours without the standard preloading dose.

They included 70 patients with a mean age of 63.7 years that had been admitted as emergencies with ADHF.

Levosimendan was titrated over 2 hours from 0.05 mcg/kg/min to the maintenance dose of 0.2 mcg/kg/min without the standard loading dose. Treatment was continued for up to 72 hours, according to clinical improvement, as determined by New York Heart Association (NYHA) classification, chest auscultation, and X-ray.

As a single treatment group compared with baseline, there were significant reductions in BNP after 48 hours (P < .001) and 72 hours (P < .001), while the signal-averaged electrocardiogram late potentials of fQRSd only showed a significant reduction after 72 hours (P = .04).

For further analysis, patients were divided according to treatment times (<=24 h, n = 14; 24-48 h, n = 35; 48-72 h, n = 21). For BNP, the 24-hour group showed no significant differences from baseline at all time points. In contrast, the 48-hour group showed a significant decrease in BNP at 48 hours (1,215 vs 748 pg/mL; P < .0001), as did the 72-hour group (912 vs 601 pg/mL; P < .04). This significance was maintained to 72 hours (912 vs 535 pg/mL; P < .004).

The 24-hour group also showed no significant improvements in fQRSd at all time points. The 48-hour groups showed a trend for improved fQRSd after 72 hours (145 vs 140 ms; P = .06). The 72-hour group was just at significance at 72 hours (153 vs 147; P = .05).

While the combination of optimal BNP decrease and optimal fQRSd response was only seen in patients after 72 hours of infusion, Dr. Aidonidis said the benefits of this up-titration of levosimendan with more than 24 hours of infusion without a loading dose were similar to those seen in previous trials, and confirmed that this agent has a beneficial neurohormonal response and a low arrhythmogenic profile, Dr. Aidonidis concluded.

HF2008 is the annual congress of the European Society of Cardiology.

[Presentation title: Efficacy and Safety of Prolonged Levosimendan Infusion in Patients With Acute Heart Failure. Abstract P270]

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