This study investigated the pharmacodynamic effects of the oral direct thrombin inhibitor ximelagatran on platelet activation and thrombin generation in patients with nonvalvular atrial fibrillation. Using an open, group-matched study design, the effects of ximelagatran (36 mg twice daily for 5 days) were studied in 12 patients with permanent nonvalvular atrial fibrillation and in 12 healthy controls. After ximelagatran for 5 days, elevated platelet P-selectin expression in atrial fibrillation patients was lowered to that during coumarin treatment or in controls but had no effect in control subjects. Using the endogenous thrombin potential as a marker, ximelagatran decreased and delayed thrombin generation in both groups. In conclusion, direct thrombin inhibition with ximelagatran reduced elevated platelet P-selectin expression and inhibited thrombin generation.
Copyright 2003 S. Karger AG, Basel