Copyright © 1999 by the European Society of Cardiology.
Sulfonylureas and ischaemic preconditioning; a double-blind, placebo-controlled evaluation of glimepiride and glibenclamide
a Department of Medicine, Division of Cardiology, J. W. Goethe University, Frankfurt/Main, Germany
b Department of Cardiology, Klinik Nordrhein, Bad Nauheim, Germany
c Division of Cardiology, University Hospital, University of Zurich, Zurich, Switzerland
d Division of Biometry, Farmovs Research Centre for Clinical Pharmacology and Drug Development, University of the Orange Free State, Bloemfontein, South Africa
revised July 3, 1998; accepted July 12, 1998
Abstract
Aims
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.
Methods and Results
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: 1·162mg), glibenclamide (15 patients: 2·54mg) or placebo (15 patients) were intravenously administered over 12min. Dilatation 3 started 10min after the beginning of the drug administration.
Mean ST segment shifts in the placebo group decreased by 35% (dilatation 2: 0·23; dilatation 3: 0·15mV; CI –0·55 to 0·00mV;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: 0·23mV; CI –0·21 to –0·02mV;P=0·01). There was little influence however, on mean ST segment shifts in the glibenclamide group (dilatation 2 and dilatation 3: 0·24mV; CI –0·10 to 0·25mV;P=0·34). Accordingly, time to angina during balloon occlusion slightly increased (by 30%) in the placebo group (dilatation 2: 37s; dilatation 3: 48s; CI 0·0 to 15·0s;P=0·16); increased by 13% in the glimepiride group (dilatation 2: 40s; dilatation 3: 45s; CI 0·0 to 14·0s;P=0·023); and remained unchanged in the glibenclamide group (dilatation 2 and dilatation 3: 30s; CI –7·5 to 7·5s;P=0·67).
Conclusion
These results show that glimepiride maintains myocardial preconditioning, while glibenclamide might be able to prevent it.
Key Words: Glimepiride, glibenclamide, ischaemic preconditioning, percutaneous transluminal coronary angioplasty
f1 Correspondence: Prof. Dr Harald Klepzig, J. W. Goethe University, Department of Medicine, Division of Cardiology, Theodor Stern Kai 7, D-60590 Frankfurt/Main, Germany.
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