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Rivaroxaban takes off as alternative to warfarin

By Ed Susman on December 9, 2010 for The Medical Post

Doctors may soon have a second alternative to warfarin in preventing strokes and emboli in patients with atrial fibrillation—the oral direct factor Xa inhibitor rivaroxaban.

In one of the featured presentations at the AHA meeting, doctors said their study showed rivaroxaban (Xarelto)—which, unlike warfarin, does not require regular monitoring or food restrictions—was at least non-inferior to warfarin treatment.

“Rivaroxaban is a proven alternative to warfarin for moderate- to high-risk patients with atrial fibrillation,” said Dr. Robert Califf, a professor of medicine at Duke University in Durham, N.C., in presenting results of ROCKET AF (Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation).

Two alternatives:

The highly anticipated ROCKET AF results appear to give clinicians at least two alternatives to warfarin for anticoagulation in patients with AF. Recent studies with the oral direct thrombin inhibitor dabigatran (Pradax) have also shown it to be a possible alternative to warfarin. Bayer’s rivaroxaban and Boehringer Ingelheim’s dabigatran are both approved in Canada for prevention of venous thromboembolic events in patients who have undergone elective total hip or knee replacement. In addition, dabigatran recently received a new indication for prevention of stroke and systemic embolism in AF.
“Do we need two drugs besides warfarin for anticoagulation?” asked Dr. Ray Gibbons, a professor of medicine at the Mayo Clinic in Rochester, Minn., who was not involved in the study. “Yes, if for no other reason than that competition may reduce health-care costs.”

Warfarin, although effective, is often not prescribed, or patients fail to adhere to therapy. The treatment is inconvenient, requires regular monitoring and has numerous side-effects. Doctors have been hoping to find an alternative for decades.

In the ROCKET AF trial, researchers in 45 countries enrolled more than 14,000 patients, including 750 in Canada. The 7,131 patients randomly assigned to rivaroxaban received a dose of 20 mg daily and the 7,133 assigned to warfarin were attempting to maintain a target INR of 2.5. Patients on warfarin had a rate of stroke or non-central nervous system embolism of 2.16 per 100 patient-years, compared with 1.71 per 100 patient-years for those on rivaroxaban, achieving statistical significance for non-inferiority.

The co-primary endpoint—to determine if rivaroxaban was actually superior to warfarin—missed achieving statistical significance according to an intention-to-treat analysis. If the study included only those patients who were adherent to treatment, then it appeared rivaroxaban did achieve superiority, Dr. Califf reported.

In terms of safety, 55 patients in the rivaroxaban arm experienced intracranial bleeding compared with 84 in the warfarin arm, a significant difference.

However, the apparent safety advantage of rivaroxaban was questioned by Dr. Elaine Hylek, the paper’s discussant and an associate professor of medicine at Boston University. “There were fewer intracranial bleeds on rivaroxaban and fewer deaths from bleeding,” she said. “However, there were more hemorrhages requiring transfusion and drops in hematocrit, rendering the overall safety profile less clear.”

Among the warfarin patients the median time spent within therapeutic range was just 57.8%.

Dr. Hylek suggested the intention-to-treat analysis, rather than the per-protocol analysis, reflected the real-world situation better and indicates the effectiveness of the two treatments is similar.

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Rivaroxaban takes off as alternative to warfarin

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