The clinical effects of levosimendan are not attenuated by sulfonylureas

Scand Cardiovasc J. 2012 Dec;46(6):330-8. doi: 10.3109/14017431.2012.725206. Epub 2012 Sep 25.

Abstract

Objectives: 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.

Design: 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / metabolism
  • Drug Interactions
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / epidemiology
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Hemodynamics / drug effects
  • Humans
  • Hydrazones / adverse effects
  • Hydrazones / therapeutic use*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • KATP Channels / drug effects
  • KATP Channels / metabolism
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Propensity Score
  • Proportional Hazards Models
  • Pyridazines / adverse effects
  • Pyridazines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Simendan
  • Sulfonylurea Compounds / adverse effects
  • Sulfonylurea Compounds / therapeutic use*
  • Treatment Outcome
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*

Substances

  • Hydrazones
  • Hypoglycemic Agents
  • KATP Channels
  • Pyridazines
  • Sulfonylurea Compounds
  • Vasodilator Agents
  • Simendan