The calcium sensitizer levosimendan and cardiac arrhythmias: an analysis of the safety database of heart failure treatment studies.
BACKGROUND
Levosimendan is a calcium sensitizer that increases the contractility of the myofilaments and is considered not to affect cardiac electrophysiology. We assessed its potential to generate cardiac arrhythmias by analysing ECG recordings from clinical studies on intravenously administered levosimendan in heart failure patients.


RESULTS
The database consisted of continuous 1-day recordings, of which 366 were during levosimendan and 142 during placebo comparison. Supraventricular (SVT) and ventricular tachycardia (VT) were defined as > or =3 premature complexes at a rate > or = 120/min. No difference appeared between levosimendan and control groups in the occurrence of atrial fibrillation (12% vs 13%), SVT (28% vs 30%), or VT (41% vs 44% of all recordings; all p = NS). Also the frequency of VT was similar (0.55 +/- 3.89 vs 0.20 +/- 1.08 episodes/h; p = NS). No torsade de pointes or sustained VT occurred.


CONCLUSIONS
Short-term levosimendan therapy of heart failure showed no tendency to increase cardiac arrhythmias. Although assessing only surrogates of prognostically significant arrhythmias, the findings together with previously observed reduction of mortality in heart failure therapy studies support the presumption that levosimendan has an electrophysiologically neutral profile.
Lilleberg
Jyrki
J
Department of Medicine, Helsinki University Central Hospital, Sairaalakatu, Vantaa, Finland.
Ylönen
Vesa
V
Lehtonen
Lasse
L
Toivonen
Lauri
L
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D011336:Probability; D011724:Pyridazines / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012042:Registries; D018570:Risk Assessment; D000077464:Simendan; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan