stroke prevention using the oral direct thrombin inhibitor ximelagatran in patients with nonvalvular...

Stroke Prevention Using the Oral Direct Thrombin Stroke Prevention Using the Oral Direct Thrombin Inhibitor Ximelagatran in Patients With Nonvalvular Inhibitor Ximelagatran in Patients With Nonvalvular

Atrial Fibrillation Atrial Fibrillation

Stroke Prevention Using the Oral Direct Thrombin Stroke Prevention Using the Oral Direct Thrombin Inhibitor Ximelagatran in Patients With Nonvalvular Inhibitor Ximelagatran in Patients With Nonvalvular

Atrial Fibrillation Atrial Fibrillation

SPORTIF V TrialSPORTIF V Trial

Presented atPresented atAmerican Heart AssociationAmerican Heart Association

Scientific Sessions 2003Scientific Sessions 2003

Presented By Jonathan L Halperin, M.D.Presented By Jonathan L Halperin, M.D.

www. Clinical trial results.org

Ximelagatran (36 mg bid) A novel, oral direct thrombin

inhibitor ximelagatran(n = 1,960)

Ximelagatran (36 mg bid) A novel, oral direct thrombin

inhibitor ximelagatran(n = 1,960)

Warfarin Target INR 2.0-3.0

(n = 1,962)

Warfarin Target INR 2.0-3.0

(n = 1,962)

Endpoints (mean follow-up 20 months): Primary – All strokes (ischemic or hemorrhagic) and systemic embolic

events, based on an intention-to-treat analysis for non-inferiority Secondary – Composite of death, stroke, systemic embolism, and MI; and

safety variables, specifically bleeding and liver enzyme elevations

Endpoints (mean follow-up 20 months): Primary – All strokes (ischemic or hemorrhagic) and systemic embolic

events, based on an intention-to-treat analysis for non-inferiority Secondary – Composite of death, stroke, systemic embolism, and MI; and

safety variables, specifically bleeding and liver enzyme elevations

SPORTIF V TrialSPORTIF V TrialSPORTIF V TrialSPORTIF V Trial

AHA 2003 Late Breaking TrialsAHA 2003 Late Breaking Trials

Randomized Double-blind to:Randomized Double-blind to:

3,922 patients with nonvalvular AF and risk factors for stroke (previous stroke, hypertension, or

CHF)

3,922 patients with nonvalvular AF and risk factors for stroke (previous stroke, hypertension, or

CHF)


1.6%

1.2%

0%

1%

2%

1.6%

1.2%

0%

1%

2%

SPORTIF V Trial: Strokes (ischemic or SPORTIF V Trial: Strokes (ischemic or hemorrhagic) and Systemic Embolic Events hemorrhagic) and Systemic Embolic Events

SPORTIF V Trial: Strokes (ischemic or SPORTIF V Trial: Strokes (ischemic or hemorrhagic) and Systemic Embolic Events hemorrhagic) and Systemic Embolic Events

WarfarinWarfarinXimelagatran Ximelagatran

Intent-to-Treat Absolute 0.45% annual in ximelagatran arm

(95% CI -0.13-1.03, p=0.13)Met non-inferiority hypothesis


Eve

nt

Rat

e (%

per

yea

r)E

ven

t R

ate

(% p

er y

ear)

In As-Treated Analysis: Absolute 0.55% annual

in ximelagatran arm 95% CI -0.06-1.16

p=0.089


0.6%

2.4%

0.6%

3.1%

0%

2%

4%

6% Ximelagatran

Warfarin

0.6%

2.4%

0.6%

3.1%

0%

2%

4%

6% Ximelagatran

Warfarin

SPORTIF V Trial: Bleeding EventsSPORTIF V Trial: Bleeding EventsSPORTIF V Trial: Bleeding EventsSPORTIF V Trial: Bleeding Events


p=NS

p=NS

ICH Major Bleed

Eve

nt

Rat

e (%

per

yea

r)E

ven

t R

ate

(% p

er y

ear)


6.0%

0.8%

0%

2%

4%

6%

8%

10%

6.0%

0.8%

0%

2%

4%

6%

8%

10%

SPORTIF V Trial: Liver Enzyme ElevationSPORTIF V Trial: Liver Enzyme ElevationSPORTIF V Trial: Liver Enzyme ElevationSPORTIF V Trial: Liver Enzyme Elevation


ALT >3x ULNp<0.001



5.8%6.3%

0%

2%

4%

6%

8%

10%

5.8%6.3%

0%

2%

4%

6%

8%

10%

SPORTIF V Trial: Combined Major Adverse EventsSPORTIF V Trial: Combined Major Adverse EventsOn-Treatment AnalysisOn-Treatment Analysis

SPORTIF V Trial: Combined Major Adverse EventsSPORTIF V Trial: Combined Major Adverse EventsOn-Treatment AnalysisOn-Treatment Analysis


Primary Events +Major Bleeding + Death

p=0.527


Eve

nt

Rat

e (%

per

yea

r)E

ven

t R

ate

(% p

er y

ear)

stroke prevention using the oral direct thrombin inhibitor ximelagatran in patients with nonvalvular...

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