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European Journal of Heart Failure 2007 9(2):202-208; doi:10.1016/j.ejheart.2006.06.001
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© 2007 European Society of Cardiology

Levosimendan and prostaglandin E1 for uptitration of beta-blockade in patients with refractory, advanced chronic heart failure

Rudolf Berger*, Deddo Moertl, Martin Huelsmann, Anja Bojic, Roozbeh Ahmadi, Isabella Heissenberger and Richard Pacher

Department of Cardiology, Medical University of Vienna Waehringer Guertel 18-20, A-1090, Vienna, Austria Ludwig Boltzman Institute of Cardiovascular Research Vienna, Austria

* Corresponding author. Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria. Tel.: +43 1404004616; fax: +43 14081148. E-mail address: rberger{at}gmx.at


  Abstract

Background: In advanced chronic heart failure (CHF) 20% of patients do not tolerate beta-blockers and 50% do not reach target doses.

Aim: To test whether levosimendan or prostaglandin E1 (PGE1) can facilitate uptitration of beta-blockers in advanced CHF.

Methods and results: Seventy-five advanced CHF patients (LVEF<35%, NYHA class IIIb or IV) intolerant to beta-blocker uptitration to target doses (10 mg bisoprolol/day) were randomised to a monthly 24 h infusion with levosimendan (n=39) or a chronic infusion with PGE1 (n=36) for 3 months. Bisoprolol was uptitrated following predefined criteria. At 12 weeks, bisoprolol dose increased from 4 mg to 10 mg in both groups. Heart failure worsening occurred in 29 levosimendan patients (74%) versus 16 PGE1 patients (44%, p=0.008). Uptitration was impossible in 9 levosimendan patients (23%) versus 2 PGE1 patients (6%, p=0.03). The combined endpoint of death or urgent heart transplantation or implantation of a ventricular assist device was reached by 12 levosimendan patients (31%) versus 4 PGE1 patients (11%, p=0.04). After 1 year, LVEF increased from 23±7% to 28±11% (p=0.0004), and BNP decreased from 994±806 to 659±564 pg/ml (p=0.03).

Conclusion: Levosimendan and PGE1 facilitate uptitration of beta-blockers in previously intolerant CHF patients. PGE1 treatment allowed uptitration in more patients and resulted in a better clinical outcome compared to levosimendan. This approach increased LVEF and decreased BNP after 1 year.

Key Words: Heart failure • Beta-blocker • Positive inotropes • Vasodilators

Received June 21, 2005; Revised April 20, 2006; Accepted June 5, 2006


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