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More Evidence of Cardiovascular Safety of Second-Generation Sulfonylureas

Diabetes patients who used second-generation sulfonylureas had no excess one-year mortality after a myocardial infarction, researchers said….

A community study of patients treated for MI found that the 12-month survival for diabetes patients using second-generation sulfonylureas was about 95%, versus a one-year survival of 90% for non-diabetic MI patients (P0.001), Moreover, diabetes patients treated with second-generation sulfonylureas also had significantly better one-year survival than diabetes patients using diet alone or insulin (P0.001).

After adjusting for age, sex, reperfusion, and duration of diabetes, only use of insulin was associated with excess mortality and the risk was greatest among patients with the longest history of diabetes, he said. “There was no association between sulfonylurea use and excess mortality,” he said.

The concern about increased cardiovascular mortality with sulfonylureas emerged in the early 1970s, when first-generation drugs in this class began to be widely used. The likely mechanism for increased mortality was the drug’s ability to bind to adenosine triphospate-sensitive potassium channels in pancreatic beta cells — ironically the same mechanism that made the drug effective in treating diabetes.

In pancreatic cells, binding ATP keeps the potassium channels closed, which triggers an influx of calcium ions into the cell, promoting increased release of insulin via exocytosis of insulin-containing granules.

The downside to the first-generation sulfonylurea drugs was that they were not specific to ATP-sensitive potassium channels in the pancreas, but also binded to ATP-sensitive potassium channels in heart cells and vascular smooth-muscle cells. In the heart and the vasculature, this binding action impairs coronary blood flow, which limits control of ischemic damage during myocardial infarction.

But studies of second-generation sulfonylureas have reported that the drugs may reduce the risk of MI.

Against that background, Dr. Patch and colleagues studied the question of the impact of second-generation sulfonylureas on survival following MI.

They analyzed outcomes data from 2,732 MIs that occurred in Olmsted County, Minn., from 1979 through 2002. The average age of patients was 70, and women made up 56% of the cohort.

Four hundred eighty-six of the MI patients had diabetes and 24% of them used second-generation sulfonylureas, 47% used insulin, while 22% relied on diet alone for management of diabetes.

Five hundred eight MI patients died within a year of the incident MI.  Compared with non-diabetic MI patients, patients with diabetes were more likely to be overweight or obese, hyperlipidemic, and to have received urgent reperfusion therapy during hospitalization for treatment of the incident MI.

Practice Pearl:
Explain to interested patients that this study suggests that newer sulfonylureas do not increase the risk of death among diabetes patients who use the drugs after heart attacks.

Patch RK, et al “Treatment of diabetes and outcome after myocardial infarction: a community study” AHA Meeting 2007; Abstract 3588.