Outcomes for Ximelagatran Compared with Warfarin According to INR Control: Results from SPORTIF III and V Atrial Fibrillation Trials.

Abstract

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 ModerateStroke/SEE, %/yr2.101.341.07P = 0.09P = 0.02P < 0.01Total mortality, %/yr4.201.841.69P < 0.01P < 0.01P < 0.01Major bleeding, %/yr3.851.961.58P < 0.01P < 0.01P < 0.01