title: The clinical effects of levosimendan are not attenuated by sulfonylureas.
abstract: OBJECTIVE
  Levosimendan is an inodilator indicated for acute heart failure (AHF). Its vasodilatory and anti-ischemic effects are mediated by the opening of ATP-dependent potassium channels (K(ATP) channels). Diabetes mellitus is common in AHF patients and sulfonylureas are often prescribed. Sulfonylureas act by blocking the K(ATP) channels. An interaction between levosimendan and sulfonylureas has been shown in preclinical models and could be hypothesized in clinical practice.
  
  
  METHODS
  We produced a pooled analysis of six randomized levosimendan trials (in total of 3004 patients of which 1700 were treated with levosimendan and 226 both with levosimendan and sulfonylureas) with the aim to study the influence of concurrent sulfonylurea treatment to the levosimendan effects. Invasive and non-invasive hemodynamics, biomarkers (BNP), adverse events related to myocardial ischemia, and survival were evaluated.
  
  
  RESULTS
  In our relatively small data set, we could not detect any clinically relevant interactions between the sulfonylureas and levosimendan. Similar decreases in systolic and diastolic blood pressure, pulmonary capillary wedge pressure and BNP, and similar survival and adverse event profiles were seen in sulfonylurea users and non-users exposed to levosimendan.
  
  
  CONCLUSIONS
  Concomitant use of sulfonylureas with levosimendan does not attenuate the hemodynamic or other effects of levosimendan.
authors.affiliation: Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. matti.kivikko@hus.fi
authors.forename: Matti
authors.initials: M
authors.lastname: Kivikko
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Piero
authors.initials: P
authors.lastname: Pollesello
authors.forename: Pasi
authors.initials: P
authors.lastname: Pohjanjousi
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
mesh_terms: D000368:Aged; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000009:adverse effects / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D057216:Propensity Score; D016016:Proportional Hazards Models; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D000077464:Simendan; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D006835:Hydrazones; D007004:Hypoglycemic Agents; D054086:KATP Channels; D011724:Pyridazines; D013453:Sulfonylurea Compounds; D014665:Vasodilator Agents; D000077464:Simendan