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.
Outcome Poor INR Control Moderate INR Control Good INR Control Poor vs Moderate Poor vs Good Good 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
Considerations for routine coagulation monitoring with rivaroxaban: A case report and review of the literature
