Results from a major international trial indicate that the oral direct thrombin-inhibitor ximelagatran may be a safe and effective alternative to warfarin as a stroke preventive in patients with atrial fibrillation, according to the report in the November 22nd issue of The Lancet.

Ximelagatran was developed as an oral alternative to warfarin that might have an enhanced safety profile in terms of increased risk for bleeding and interactions with food and medications. In the current work, the SPORTIF III Trial (Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation III), 3,407 patients from Europe, Asia, and Australia with atrial fibrillation and 1 or more stroke risk factors were randomized to warfarin or oral ximelagatran (average follow-up, 17 months).

Oral ximelagatran was a little more effective in reducing the frequency of stroke or systemic thromboembolism than warfarin, although the difference was not statistically significant (relative risk reduction 30 percent, absolute risk reduction 0.7 percent for ximelagatran). Rates of disabling or fatal stroke, death, and major bleeding were similar for the 2 groups.

Lead investigator Dr. S Bertil Olsson commented, "We have shown that ximelagatran, administered in a fixed dose without coagulation monitoring, protects high-risk patients with atrial fibrillation against thromboembolism at least as effectively as well-controlled warfarin, and is associated with less bleeding. The preliminary reported SPORTIF V trial presented at the November 2003 American Heart Association meeting has further verified the efficacy and safety in a similar population."

In an accompanying Commentary, Dr. Freek Verheugt concluded, "If safety seems good in a broader population of patients, ximelagatran may find its way into general use in atrial fibrillation. But this process will take a while, and in the meantime the ACTIVE study with clopidogrel, which has a more established safety profile than ximelagatran so far, will be finished. Depending on the outcome, physicians willing to switch from warfarin for patients with atrial fibrillation must decide which agent they will go for."