BACKGROUND: Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoagulable or prothrombotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional warfarin, and aspirin. (300 mg) therapy on thrombogenesis and platelet activation in AF. METHODS AND RESULTS: We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomization to either 1 mgwarfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) with samples taken 2 and 6 weeks later. Pretreatment results were compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-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 beta-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median beta-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. CONCLUSIONS: 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 beta-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 suggests that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.
RCT Entities:
BACKGROUND: Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoagulable or prothrombotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional warfarin, and aspirin. (300 mg) therapy on thrombogenesis and platelet activation in AF. METHODS AND RESULTS: We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomization to either 1 mg warfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) with samples taken 2 and 6 weeks later. Pretreatment results were compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-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 beta-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median beta-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. CONCLUSIONS: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 beta-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 suggests that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.
Authors: Gregory Y H Lip; Lars H Rasmussen; S Bertil Olsson; Eva Jensen; Bengt Hamrén; Ulf G Eriksson; Karin Wåhlander Journal: Br J Clin Pharmacol Date: 2015-09-22 Impact factor: 4.335
Authors: Andreas Goette; Jonathan M Kalman; Luis Aguinaga; Joseph Akar; Jose Angel Cabrera; Shih Ann Chen; Sumeet S Chugh; Domenico Corradi; Andre D'Avila; Dobromir Dobrev; Guilherme Fenelon; Mario Gonzalez; Stephane N Hatem; Robert Helm; Gerhard Hindricks; Siew Yen Ho; Brian Hoit; Jose Jalife; Young-Hoon Kim; Gregory Y H Lip; Chang-Sheng Ma; Gregory M Marcus; Katherine Murray; Akihiko Nogami; Prashanthan Sanders; William Uribe; David R Van Wagoner; Stanley Nattel Journal: Heart Rhythm Date: 2016-06-10 Impact factor: 6.343