Sulfonylureas and ischaemic preconditioning - A double-blind, placebo-controlled evaluation of glimepiride and glibenclamide

Aims Glimepiride is a new sulfonylurea for diabetes treatment which is supp osed to impact less on extrapancreatic ATP-dependent K+ channels than the c onventional drug glibenclamide. This study was performed to evaluate whethe r this results in a better maintenance of ATP-dependent K+ channel mediated ischaemic myocardial preconditioning. Methods and Results In a double-blind placebo-controlled study the period o f total coronary occlusion during balloon angioplasty of high grade coronar y artery stenoses was used as a model to compare the effects of both drugs. Quantification of myocardial ischaemia was achieved by recording the intra coronary ECG and the time to the occurrence of angina during vessel occlusi on. All patients underwent three dilatations. The first dilatation (dilatat ion 1) served to determine the severity of ischaemia during vessel occlusio n. During dilatation 2, baseline values were recorded. Thereafter, glimepir ide (15 patients: 1.162 mg), glibenclamide (15 patients: 2.54 mg) or placeb o (15 patients) were intravenously administered over 12 min. Dilatation 3 s tarted 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 r eduction also occurred in the glimepiride group, in which repetitive balloo n 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 dilata tion 3: 0.24 mV; CI -0.10 to 0.25 mV; P = 0.34). Accordingly, time to angin a 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); incr eased by 13% in the glimepiride group (dilatation 2: 40 s; dilatation 3: 45 s; CI 0.0 to 14.0 s; P = 0.023); and remained unchanged in the glibenclami de group (dilatation 2 and dilatation 3. 30 s; CI -7.5 to 7.5 s; P = 0.67). Conclusion These results show that glimepiride maintains myocardial precond itioning, while glibenclamide might be able to prevent it.