COPENHAGEN — Newer-generation sulfonylureas appear to be associated with lower post-myocardial infarction mortality in diabetic patients than are the older-generation agents, Dr. Henriette Thisted reported at the annual meeting of the European Association for the Study of Diabetes.
Sulfonylureas can block the adenosine triphosphate-sensitive potassium channels in the heart, thereby inhibiting the myoprotective effects of ischemic preconditioning. However, recent data suggest only glibenclamide inhibits this protection, whereas newer sulfonylureas, such as gliclazide and glimepiride, do not. The clinical implications of these differences are still unclear because data are sparse, said Dr. Thisted, of the department of clinical epidemiology at Aarhus (Denmark) University Hospital.
Earlier this year, Dr. Thisted and her associates published preliminary findings from a regional Danish hospital database, in which they found a lower rate of MI in patients using gliclazide and glimepiride, compared with those using other sulfonylureas, and a trend toward lower 30-day post-MI mortality in users of gliclazide, compared with users of other sulfonylureas (Am. J. Ther. 2006;13:134–40).
They have now expanded the study nationwide to include 72,913 first-time admissions for MI during 1996–2004 from the Danish National Patient Registry.
The researchers used a national prescription database to identify 3,992 patients as sulfonylurea users, including 2,554 who were taking the “old” sulfonylureas glibenclamide, glipizide, or tolbutamide and 1,438 users of the “new” agents gliclazide or glimepiride.
Those using the older sulfonylureas were older than those using the new agents (73.3 vs. 71.6 years) and had a longer duration of diabetes (14.4% vs. 10.6% had been diagnosed for more than 10 years). They also tended to have more comorbidities.
At 30 days following MI, 24.1% of the old sulfonylurea users had died, compared with 17.9% of the new-agent user group. After adjustment for age, sex, socioeconomic status, diabetes duration, comorbidity index, discharge diagnoses, and use of relevant medications, the new sulfonylurea users still had a 23% lower 30-day mortality rate than did the old-agent users, Dr. Thisted reported.
This apparent advantage in 30-day mortality with new sulfonylureas was also evident during the entire follow-up period, with a mean of 1.68 years: The adjusted mortality rate ratio was 0.78, or a 22% lower risk of death post MI.
For the individual older agents, mortality was 61.7% in the 877 glibenclamide patients, 61.5% of the 436 tolbutamide patients, and 60.9% of the 412 who had been taking glipizide. With the newer agents, 47.9% of the 167 taking gliclazide and 40.7% taking glimepiride died during follow-up.