Patients with atrial fibrillation have an increased risk of stroke due to the formation of blood clots in the heart. Coumadin has been shown to significantly reduce the risk of stroke in these patients. But coumadin is a difficult drug to use correctly - careful monitoring of the INR (a measure of "blood thinness") and frequent adjusting of coumadin dosage is necessary to assure effective treatment and to reduce the risk of coumadin-induced bleeding complications.
Ximelagatran, on the other hand, can be given as a simple twice per day dose, with no monitoring of blood tests or dosage adjustments.
SPORTIF V was a randomized double-blind trial comparing ximelagatran with coumadin in patients with atrial fibrillation. The study was designed as a "non-inferiority" trial, that is, it was designed to show that ximelagatran was no worse than coumandin. Blood was drawn frequently and "dosage adjustments" were ostensibly made in both groups, so that patients and doctors would not know which drug they were really receiving. Coumadin dosages were, in fact, controlled with extreme care in this study to assure optimal therapy.
Overall, 3922 patients were randomized to receive either coumadin or ximelagatran in this trial. At the end of the study, there was no difference in the risk of stroke between coumadin and ximelagatran - that is, ximelagatran was at least as effective as coumadin. While the risk of major bleeding complications was low in both groups and not significantly different between groups, the overall risk of bleeding complications was significantly lower with ximelagatran.
One question remains for ximelagatran - elevations in liver enzymes were seen in 6% of patients taking the new drug. Typically, this elevation in enzymes was seen over the first 6 months of treatment, and then normalized even if the drug was continued. The significance of this transient liver enzyme elevation is thought to be minor, but more study will need to be done.
Overall, it appears that ximelagatran will be a major advance in the treatment of clotting disorders, as it seems to be as effective as coumadin while avoiding the cumbersome steps, to both the patient and the doctor, required to use coumadin safely. AstraZeneca, makers of ximelagatran, is hoping to have FDA approval to market this drug in 2004.
