Author + information
Garratt et al. (1)are to be congratulated on their excellent retrospective study, which suggests that sulfonylurea hypoglycemic drugs increase early mortality after direct angioplasty for acute myocardial infarction. The data suggest that the increased mortality associated with the sulfonylurea drugs is due to pump dysfunction with cardiogenic shock. Unfortunately, the report does not include a breakdown of the causes of in-hospital or late mortality. One might predict that because early mortality was higher in the sulfonylurea group, and these were presumably the higher risk patients, late mortality would be less in this group. This predicted decreased risk would be cancelled if the increased risk associated with the sulfonylurea drugs continues, as is likely to be the case. Other information that is missing from this study is when the patients who died took their last dose of sulfonylurea and what sulfonylurea drug they were taking. The most likely mechanism of toxicity of the sulfonylureas drugs—abolishing ischemic preconditioning through inhibition of the KATPchannel—would require the presence of a substantive amount of the drug at the time of the myocardial infarction owing to recent intake or a long half-life of the drug in the body.
This study provides further evidence that patients are dying unnecessarily from use of a sulfonylurea drug. It supports the findings of the randomized, controlled trials, such as the University Group Diabetes Program (UGDP) Study (2,3)and the recently published United Kingdom Prospective Diabetes Study (UKPDS) (4,5). The UGDP study demonstrated increased cardiovascular mortality in tolbutamide-treated patients as compared with those who received placebo. The UKPDS trial showed a similar reduction of blood glucose with sulfonylurea drugs and metformin as compared with diet, but there was no reduction in cardiovascular events with sulfonylurea drugs (4)and a highly statistically significant reduction in cardiovascular events with metformin (5). Therefore, there is substantial reason for exercising caution with the prescription of sulfonylurea drugs to diabetic patients. We have done a meta-analysis of studies of diabetic patients who had a myocardial infarction and found that the chances of dying are increased if the patient is taking a sulfonylurea drug versus following a diet alone (unpublished data). If Garratt et al. (1)could separate the group 2 patients into those treated with diet alone, insulin or other hypoglycemic drugs, we could add their results to our meta-analysis. These data, along with the other information mentioned earlier, could be published in response to this letter.
In the meantime, it is essential that doctors become more aware of the risks of the sulfonylurea hypoglycemic drugs and use them cautiously, when all other therapeutic options have been exhausted.
- American College of Cardiology
- Garratt K.N.,
- Brady P.A.,
- Hassinger N.L.,
- Grill D.E.,
- Terzic A.,
- Holmes D.R. Jr.
- ↵The University Group Diabetes Program. A study of the effect of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VI. Supplementary report on nonfatal events in patients treated with tolbutamide. Diabetes 1976;25:1129–53.
- The University Group Diabetes Program. A study of the effect of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. Diabetes 1970;19 Suppl 2:7789–830.
- ↵United Kingdom Prospective Diabetes Study (UKPDS). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–53.
- ↵United Kingdom Prospective Diabetes Study (UKPDS). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854–65.