CLINICAL STUDY
A prospective randomized trial of aspirin-clopidogrel combination therapy and dose-adjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation
Sridhar Kamath, MRCPa,
Andrew D. Blann, PhD, MRCPatha,
Bernard S. P. Chin, MRCPa and
Gregory Y. H. Lip, MD, FACCa,*
a Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom
Manuscript received March 1, 2002;
revised manuscript received April 16, 2002,
accepted May 7, 2002.
* Reprint requests and correspondence: Prof. Gregory Y. H. Lip, Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, United Kingdom.
g.y.h.lip{at}bham.ac.uk
OBJECTIVES: This study was designed to investigate whether or not combination aspirin-clopidogrel therapy would reduce markers of thrombogenesis and platelet activation in atrial fibrillation (AF), in a manner similar to warfarin.
BACKGROUND: Dose-adjusted warfarin is beneficial as thromboprophylaxis in AF, but potentially serious side effects and regular monitoring leave room for alternative therapies.
METHODS: We randomized 70 patients with nonvalvular AF who were not on any antithrombotic therapy to either dose-adjusted warfarin (international normalized ratio 2 to 3) (Group I) or combination therapy with aspirin 75 mg and clopidogrel 75 mg (Group II). Plasma indices of thrombogenesis (fibrin D-dimer, prothrombin fragment 1+2) and platelet activation (beta-thromboglobulin [TG] and soluble P-selectin) were quantified, along with platelet aggregation responses to standard agonists, at baseline (pretreatment) and at six weeks posttreatment.
RESULTS: Pretreatment levels of fibrin D-dimer (p = 0.001), beta-TG (p = 0.01) and soluble P-selectin (p = 0.03) were raised in patients with AF, whereas plasma prothrombin fragment 1+2 levels and platelet aggregation were not significantly different compared with controls. Dose-adjusted warfarin reduced plasma levels of fibrin D-dimer, prothrombin fragment 1+2 and beta-thromboglobulin levels at six weeks (all p < 0.001), enhanced plasma levels of soluble P-selectin (p < 0.001) and had no significant effect on platelet aggregation. Aspirin-clopidogrel combination therapy made no difference to the plasma markers of thrombogenesis or platelet activation (all p = NS), but the platelet aggregation responses to adenosine diphosphate (p < 0.001) and epinephrine (p = 0.02) were decreased.
CONCLUSIONS: Aspirin-clopidogrel combination therapy failed to reduce plasma indices of thrombogenesis and platelet activation in AF, although some aspects of ex vivo platelet aggregation were altered. Anticoagulation with warfarin may be superior to combination aspirin-clopidogrel therapy as thromboprophylaxis in AF.
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Abbreviations and Acronyms
| | ADP | | adenosine diphosphate | | AF | | atrial fibrillation | | beta-TG | | beta-thromboglobulin | | INR | | international normalized ratio |
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