Sulfonylureas and ischaemic preconditioning; a double-blind, placebo-controlled evaluation of glimepiride and glibenclamide.

Abstract

Glimepiride is a new sulfonylurea for diabetes treatment which is supposed to impact less on extra-pancreatic ATP-dependent K+ channels than the conventional drug glibenclamide. This study was performed to evaluate whether this results in a better maintenance of ATP-dependent K+ channel mediated ischaemic myocardial preconditioning. In a double-blind placebo-controlled study the period of total coronary occlusion during balloon angioplasty of high grade coronary artery stenoses was used as a model to compare the effects of both drugs. Quantification of myocardial ischaemia was achieved by recording the intracoronary ECG and the time to the occurrence of angina during vessel occlusion. All patients underwent three dilatations. The first dilatation (dilatation 1) served to determine the severity of ischaemia during vessel occlusion. During dilatation 2, baseline values were recorded. Thereafter, glimepiride (15 patients: 1.162 mg), glibenclamide (15 patients: 2.54 mg) or placebo (15 patients) were intravenously administered over 12 min. Dilatation 3 started 10 min after the beginning of the drug administration. Mean ST segment shifts in the placebo group decreased by 35% (dilatation 2: 0.23; dilatation 3:0.15 mV; CI -0.55 to 0.00 mV; P=0.049). A similar reduction also occurred in the glimepiride group, in which repetitive balloon occlusion led to a 34% reduction (dilatation 2: 0.35; dilatation 3: 0.23 mV; CI -0.21 to -0.02 mV; P=0.01). There was little influence however, on mean ST segment shifts in the glibenclamide group (dilatation 2 and dilatation 3: 0.24 mV; CI -0.10 to 0.25 mV; P=0.34). Accordingly, time to angina during balloon occlusion slightly increased (by 30%) in the placebo group (dilatation 2: 37 s; dilatation 3: 48 s; CI 0.0 to 15.0 s; P=0.16); increased by 13% in the glimepiride group (dilatation 2: 40 s; dilatation 3: 45 s; CI 0.0 to 14.0 s; P=0023); and remained unchanged in the glibenclamide group (dilatation 2 and dilatation 3: 30 s; CI -7.5 to 7.5 s; P=0.67). These results show that glimepiride maintains myocardial preconditioning, while glibenclamide might be able to prevent it.