Background: Warfarin effectively reduces the risk of stroke in patients with atrial fibrillation, but requires regular monitoring to maintain the target international normalized ratio (INR). Ximelagatran, a novel direct thrombin inhibitor, does not require coagulation monitoring and can be administered at a fixed oral dose.

Methods: Outcomes in warfarin patients (n = 3587) from the SPORTIF III and V trials according to time spent in the therapeutic target INR range of 2–3 (≥ 76% of the time = good INR control [n = 1190]; 60–75% of the time = moderate INR control [n = 1207]; and < 60% of the time = poor INR control [n = 1190]) were compared with ximelagatran patients (n = 3664). The primary endpoint was stroke/systemic embolic event (SEE).

Results: Mean follow-up was 16.6 (± 6.3) months. Outcomes in warfarin patients according to INR control are shown in the table. Ximelagatran patients had numerically lower stroke/SEE rates than the warfarin patients with poor INR control (1.43%/yr vs 2.10%/yr; P = 0.08), as well as lower mortality (2.36%/yr vs 4.20%/yr; P < 0.01) and major bleeding (1.89%/yr vs 3.85%/yr; P < 0.01). The incidence of stroke/SEE and major bleeding did not differ statistically among the moderate INR control, good INR control, and ximelagatran groups. However, major + minor bleeding was more common in the moderate INR control group than the ximelagatran group (41.8% vs 32.5%; P < 0.01).

Conclusions: In warfarin-treated atrial fibrillation patients, the risks of stroke/SEE, mortality, and major bleeding are related to INR control, with a significant reduction in these events with good vs poor INR control. Compared with the one-third of patients who experienced poor INR control, patients randomized to ximelagatran administered at a fixed oral dose without the need for coagulation monitoring had a lower mortality rate and less major bleeding.

OutcomePoor INR ControlModerate INR ControlGood INR ControlPoor vs ModeratePoor vs GoodGood vs Moderate
Stroke/SEE, %/yr 2.10 1.34 1.07 P = 0.09 P = 0.02 P < 0.01 
Total mortality, %/yr 4.20 1.84 1.69 P < 0.01 P < 0.01 P < 0.01 
Major bleeding, %/yr 3.85 1.96 1.58 P < 0.01 P < 0.01 P < 0.01 
OutcomePoor INR ControlModerate INR ControlGood INR ControlPoor vs ModeratePoor vs GoodGood vs Moderate
Stroke/SEE, %/yr 2.10 1.34 1.07 P = 0.09 P = 0.02 P < 0.01 
Total mortality, %/yr 4.20 1.84 1.69 P < 0.01 P < 0.01 P < 0.01 
Major bleeding, %/yr 3.85 1.96 1.58 P < 0.01 P < 0.01 P < 0.01 
View Large

Topics:
atrial fibrillation, international normalized ratio, sportif trial, warfarin, ximelagatran, hemorrhage, cerebrovascular accident, ischemic stroke, direct thrombin inhibitor, embolism

Author notes

Corresponding author

2005, The American Society of Hematology
2005
Sign in via your Institution