Dr Beevers
Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoaguable or prothromobotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1mg), conventional warfarin, and aspirin (300mg) therapy on thrombogenesis and platelet activation in AF.
We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and b -thromboglobulin (b -TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomisation to either 1 mg warfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) b -TG and D-dimer levels in patients with AF were elevated compared with those of control subjects (P=.001). In phase 1, there were no significant changes in median levels of fibrin D-dimer or b -TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median b -TG at 6 weeks (P=.025) and a sequential reduction in median D-dimer levels at 2 (P=.001) and 6 (P=.001) weeks compared with baseline levels.
Patients with AF have increased intravascular thrombogenesis and platelet activation compared with patients in sinus rhythm. Introduction of ultra-low-dose warfarin (1 mg) or aspirin 300 mg does not significantly alter these markers, although conventional warfarin therapy reduces b -TG and fibrin D-dimer levels. This is consistent with the beneficial effect of full-dose warfarin in preventing stroke and thromboembolism in AF and suggest that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.