title: Levosimendan and prostaglandin E1 for uptitration of beta-blockade in patients with refractory, advanced chronic heart failure.
abstract: BACKGROUND
  In advanced chronic heart failure (CHF) 20% of patients do not tolerate beta-blockers and 50% do not reach target doses.
  
  
  OBJECTIVE
  To test whether levosimendan or prostaglandin E1 (PGE1) can facilitate uptitration of beta-blockers in advanced CHF.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria. rberger@gmx.at
authors.forename: Rudolf
authors.initials: R
authors.lastname: Berger
authors.forename: Deddo
authors.initials: D
authors.lastname: Moertl
authors.forename: Martin
authors.initials: M
authors.lastname: Huelsmann
authors.forename: Anja
authors.initials: A
authors.lastname: Bojic
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Ahmadi
authors.forename: Isabella
authors.initials: I
authors.lastname: Heissenberger
authors.forename: Richard
authors.initials: R
authors.lastname: Pacher
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000527:Alprostadil / Q000494:pharmacology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain; D011379:Prognosis; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D000077464:Simendan; D013318:Stroke Volume / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D000077464:Simendan; D000527:Alprostadil