Ximelagatran

[Guest guest]

Citation: American Heart Association Scientific Sessions 2003.

The New England Journal of Medicine, Oct. 29,

New blood thinner offers first potential alternative in 50 years.

This year saw the introduction of a new, easier to manage blood

thinner pill - and the first potential alternative in 50 years to

warfarin, the standard treatment given to millions of people to

prevent blood clots.

In the Stroke Prevention Using the Oral Direct Thrombin Inhibitor

Ximelagatran In Patients with Nonvalvular Atrial Fibrillation

(SPORTIF V) trial, anticoagulation with warfarin, which reduces the

risk of ischemic stroke and other systemic and embolic events in

patients with atrial fibrillation (AF), was compared with the oral

direct thrombin inhibitor ximelagatran. Patients with AF and at

least one stroke risk factor (3,922 individuals) were randomized to

receive adjusted-dose warfarin or fixed-dose oral ximelagatran. The

primary endpoint was all strokes (ischemic and hemorrhagic) and

systemic embolic events. Primary event rates were 1.2 percent/year

in the warfarin group and 1.6 percent/year in the ximelagatran group,

not a significant difference. When all-cause mortality was included

with the primary events, the rate difference between groups by ITT

was even less, at 0.10 percent/year. Rates of disabling or fatal

stroke, hemorrhagic stroke and major bleeding did not differ

significantly between groups, but combined minor and major bleeding

was lower with ximelagatran (47 percent/year versus 37 percent/year).

In this large, double-blind trial involving high-risk patients with

AF, fixed-dose, oral ximelagatran was at least as effective as well-

controlled warfarin for preventing stroke and systemic embolic

events. It also resulted in less bleeding, confirming the results of

the SPORTIF III open-label trial.

A second study found that ximelagatran may be more effective than

warfarin in preventing blood clots after knee replacement surgery. In

that study, 2,301 patients in five countries received low or high

dose ximelagatran or warfarin for up to 12 days after surgery. Of

these 2301 patients, 1,851 were included n the analysis of drug

efficacy. Twenty percent of patients in the high-dose ximelagatran

group developed clots or died, compared with 25 percent in the lower-

dose group and 28 percent in the warfarin group.

Ximelagatran was developed as an alternative to warfarin in an effort

to find a drug that was easier for patients and doctors to manage.

While widely prescribed after strokes, heart attacks and knee

surgery, warfarin requires close laboratory monitoring for dose

adjustment, and interacts with certain foods and drugs. Studies show

ximelagatran does not require adjustments or close monitoring, and

has no food or drug interactions.