SPORTIF III

Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation III (2003)

Condition

Stroke prevention in non-valvular AF

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Objective

To establish whether ximelagatran is non-inferior to warfarin in the prevention of stroke and systemic embolism in AF

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Trial design

Randomized, open parallel group phase III study; non-inferiority trial; the primary analysis was only by intent to treat
Active treatment: ximelagatran 36 mg twice daily (n=1704)
Control treatment: warfarin (INR 2.0–3.0) (n=1703)

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Endpoints

Primary efficacy endpoint: all strokes (ischemic or hemorrhagic) and systemic embolic events
Secondary efficacy endpoints: all-cause death, cardiovascular death, fatal stroke, thromboembolic event; thromboembolic event, ischemic stroke or systemic embolism; ischemic stroke, myocardial infarction (fatal and nonfatal), hemorrhagic stroke
Primary safety endpoint: composite incidence of major and minor bleeding
Secondary safety endpoints: major bleeding, minor bleeding, adverse events

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Trial participants

3407 patients (mean age 70 years) with non-valvular AF and one or more stroke risk factors

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Results

Efficacy outcome: In the intent-to-treat population, primary events occurred in 40 of 1704 patients (1.6% per year) in the ximelagatran group and in 56 of 1703 patients (2.3% per year) in the warfarin group (absolute risk reduction 0.7%, relative risk reduction 29%). Rates of disabling or fatal stroke, mortality, and major bleeding were similar between groups. All-cause mortality was 3.2% per year in both groups
Safety outcome: The incidence of combined minor and major bleeding was 25.8% per year with ximelagatran compared to 29.8% with warfarin (relative risk reduction 14%). Adverse events occurred in 8% of the ximelagatran patients and in 4% of the warfarin patients. This difference was due to elevations of liver enzyme levels occurring more commonly with ximelagatran

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Summary

Efficacy: In high-risk patients with atrial fibrillation, fixed-dose oral ximelagatran was at least as effective as well-controlled warfarin for prevention of stroke and systemic embolic events
Safety: Ximelagatran was associated with more adverse events than warfarin, especially liver enzyme elevations. The study was prematurely terminated due to efficacy and safety endpoints

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Reference

Olsson SB for the SPORTIV III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003;362:1691-1698

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Corresponding author

Prof. S. Bertil Olsson, Department of Cardiology, University Hospital, Lund SE-221 85, Sweden, e-mail: bertil.olsson@kard.lu.se

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