Adverse cardiovascular events during treatment with glyburide (glibenclamide) or gliclazide in a high-risk population.
OBJECTIVE
Sulphonylureas promote insulin release by inhibiting pancreatic potassium channels. Older sulphonylureas such as glyburide (glibenclamide), but not newer ones such as gliclazide, antagonize similar channels in myocardium, interfering with the protective effects of ischaemic preconditioning. Whether this imparts a higher risk of adverse cardiac events is unknown.


METHODS
We conducted a population-based cohort study of patients aged 66 years and older who were hospitalized for acute myocardial infarction or who underwent percutaneous coronary intervention between 1 April 2007 and 31 March 2010 while receiving either glyburide or gliclazide. We used a high-dimensional propensity score matching process to ensure similarity of glyburide- and gliclazide-treated patients. The primary outcome was a composite of death or hospitalization for myocardial infarction or heart failure.


RESULTS
During the 2-year study period, we matched 1690 patients treated with glyburide to 984 patients treated with gliclazide at the time of hospitalization for acute myocardial infarction or percutaneous coronary intervention. We found no difference in the risk of the composite outcome among patients receiving glyburide (adjusted hazard ratio 1.01; 95% CI 0.86-1.18). We found similar results in secondary analyses of each outcome individually, and in two supplementary analyses (haemorrhage and pneumonia) in which we anticipated no difference between the two patient groups.


CONCLUSIONS
Among older patients hospitalized for acute myocardial infarction or percutaneous coronary intervention, treatment with glyburide is not associated with an increased risk of future adverse cardiovascular events relative to gliclazide, suggesting that the effect of glyburide on ischaemic preconditioning is of little clinical relevance.
Department of Medicine, University of Toronto, Toronto, ON, Canada. dnj@ices.on.ca
D N
DN
Juurlink
T
T
Gomes
B R
BR
Shah
M M
MM
Mamdani
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005907:Gliclazide / Q000008:administration & dosage* / Q000009:adverse effects; D005905:Glyburide / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D019194:Ischemic Preconditioning; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D009206:Myocardium; D009864:Ontario / Q000453:epidemiology; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D013453:Sulfonylurea Compounds; D005907:Gliclazide; D005905:Glyburide