January 1, 2005Open Access
Preventing Stroke in Atrial Fibrillation: The SPORTIF Programme
Key Result
Ximelagatran was comparable to well-controlled warfarin for preventing stroke and systemic embolic events in moderate- to high-risk atrial fibrillation patients (1.6% vs 2.3% per year; p=0.10).
Study Design
Type
RCT (n=7,000)
Structured PICO
Does ximelagatran reduce stroke and systemic embolic events in moderate- to high-risk atrial fibrillation patients compared to warfarin?
P
Population
More than 7,000 moderate- to high-risk patients with atrial fibrillation evaluated for stroke prevention over 21 months.
I
Intervention
Ximelagatran 36 mg oral twice daily
C
Comparator
Well-controlled warfarin (international normalized ratio 2.0-3.0)
O
Outcome
Stroke and systemic embolic eventshard clinical
Ximelagatran, a fixed-dose oral direct thrombin inhibitor without coagulation monitoring, is comparable to dose-adjusted warfarin for stroke prevention in moderate- to high-risk AF patients.
Main Result
Absolute Event Rate: 1.6% vs 2.3%
p-value: p=0.10
Abstract
Atrial fibrillation (AF) is the most common cardiac risk factor for stroke. Oral anticoagulants such as the vitamin K antagonist warfarin have been proven effective in reducing the risk of stroke in AF. Warfarin, however, has many disadvantages including the need for coagulation monitoring, a narrow therapeutic index, inter-/intra-patient variability and food-drug interactions. As a result, warfarin is underused in clinical practice and a viable alternative is needed. Ximelagatran, the first oral direct thrombin inhibitor, is given as a fixed dose, does not have a narrow therapeutic index, has low potential for drug interactions, has no significant food interactions and does not require coagulation monitoring. Ximelagatran has been evaluated in the Stroke Prevention using an ORal direct Thrombin Inhibitor in atrial Fibrillation (SPORTIF) trial programme, the largest clinical trials of antithrombotic therapy for stroke prevention in AF to date. The phase III trials, SPORTIF III and V, compared ximelagatran (36 mg twice daily) with well-controlled warfarin (international normalized ratio 2.0-3.0) in a combined population of more than 7,000 moderate- to high-risk AF patients. Data from SPORTIF III show an absolute reduction in stroke and systemic embolic events with ximelagatran compared with warfarin at 21 months (1.6 vs. 2.3% per year, respectively; p = 0.10). Preliminary data from SPORTIF V appear to further support non-inferiority between the two agents. On-treatment analysis of the rate of major bleeding events shows an absolute, nonsignificant reduction in the event rate per year with ximelagatran versus warfarin in both studies. The results of SPORTIF III and V demonstrate that a fixed oral dose of ximelagatran, without coagulation monitoring, is comparable to dose-adjusted warfarin in preventing stroke and other thromboembolic complications among moderate- to high-risk AF patients and has a lower rate of both major and minor bleeding. With its positive benefit-risk ratio, ximelagatran may increase the population of eligible patients for anticoagulation with AF and maximize the potential of anticoagulation in the prevention of stroke.