Effects of sulfonylurea hypoglycemic agents and adenosine triphosphate dependent potassium channel antagonists on ventricular arrhythmias in patients with decompensated heart failure.
Hypoglycemic sulfonylureas block cardiac ATP-sensitive potassium channels (K(ATP)). The opening of these channels in cardiomyocytes can induce arrhythmias. In animal studies, sulfonylureas exert an antiarrhythmic effect on the ischemic myocardium, but data on human arrhythmic events are lacking. The study population included 207 patients (age 61 +/- 14 years) admitted for decompensated CHF. The severity of ventricular arrhythmias was assessed by 24-hour Holter monitoring. None of the patients were on parenteral vasoactive therapy or antiarrhythmics during Holter recording. Diabetic patients comprised 48% of the study population, and 34% of diabetic patients were prescribed sulfonylureas. The mean hourly ventricular pairs (3.6 +/- 0.5 vs 1.8 +/- 0.3, P = 0.03), the mean hourly repetitive ventricular beats (5.7 +/- 1.0 vs 2.6 +/- 0.1, P = 0.03), and the frequency of ventricular tachycardia episodes per 24 hours (4.7 +/- 0.8 vs 2.2 +/- 0.4, P = 0.03) were significantly lower in patients with diabetes who were receiving sulfonylureas compared with nondiabetics. No significant difference occurred between patients with diabetes who were not receiving sulfonylureas and nondiabetic patients. Multivariate regression revealed a negative independent relationship between sulfonylurea therapy and hourly ventricular pairs (P = 0.03), the mean hourly repetitive ventricular beats (P = 0.03), and ventricular tachycardia episodes (P = 0.04). In a multiple logistic regression, sulfonylurea therapy was a negative predictor of repetitive ventricular beats (P = 0.01, adjusted OR, 0.31; 95% CI, 0.12-0.78). Concomitant sulfonylurea therapy may reduce the occurrence of complex ventricular ectopy in the setting of severe CHF. These results suggest that cardiac K(ATP) channel activation may be involved in the genesis of ventricular arrhythmias in CHF.
Aronson
Doron
D
Division of Cardiology, Rambam Medical Center, Haifa, Israel.
Mittleman
Murray A
MA
Burger
Andrew J
AJ
D000368:Aged; D000704:Analysis of Variance; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy*; D015716:Electrocardiography, Ambulatory; D005260:Female; D005913:Glipizide / Q000627:therapeutic use; D005905:Glyburide / Q000627:therapeutic use; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015221:Potassium Channels / Q000187:drug effects*; D012044:Regression Analysis; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D014665:Vasodilator Agents; D005905:Glyburide; D005913:Glipizide