REVIEW

Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important?

J J Meier¹, B Gallwitz², W E Schmidt², A Mügge², M A Nauck²

¹ Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
² Departments of Medicine I and II, St Josef Hospital, Ruhr-University Bochum, Bochum, Germany

Correspondence to:
Correspondence to:
Prof Dr Med Michael A Nauck
Diabeteszentrum Bad Lauterberg, Kirchberg 21, Bad Lauterberg im Harz, D-37431, Germany; m.nauck{at}diabeteszentrum.de

In the UGDP study, published in the 1970s, a high incidence of cardiovascular mortality was found in patients treated with the sulfonylurea agent tolbutamide. Impaired ischaemic preconditioning is presumed to be the most important mechanism for the excess cardiovascular mortality observed. However, as tolbutamide has only a low affinity for cardiac sulfonylurea receptors, interference with ischaemic preconditioning seems unlikely to account for this excess mortality. Several smaller studies also failed to establish a definite link between sulfonylurea treatment before acute myocardial infarction and in-hospital mortality. However, when the myocardium becomes exposed to repeated or prolonged periods of ischaemia, ischaemic preconditioning may become clinically important. Myocardial ischaemia can also develop during emergency or elective angioplasty and during coronary bypass surgery. Therefore discontinuation of sulfonylurea treatment should be considered in these circumstances.

Keywords: sulfonylureas; cardiovascular mortality; ischaemic preconditioning; myocardial infarction; type 2 diabetes

Abbreviations: DIGAMI, diabetes mellitus, insulin glucose infusion in acute myocardial infarction; SUR, sulfonylurea receptor; UGDP, university group diabetes program; UKPDS, UK prospective diabetes study

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