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

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 infusionwith levosimendan (n=39) or a chronic infusion with PGEI (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 PGEI 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 PGEI patients (11%, p=0.04). After 1 year, LVEF increased fiom 23 +/- 7% to 28 +/- 11% (p=0.0004), and BNP decreased from 994 +/- 806 to 659 +/- 564 pg/mI (p=0.03). Conclusion: Levosimendan and PGEI facilitate uptitration of beta-blockers in previously intolerant CHF patients. PGEI 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. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.