Xarelto® – Good News

Summary

Good news. A major study published in December 2010 in the  New England Journal of Medicine (NEJM) shows that the new oral “blood thinner” Xarelto® (=Rivaroxaban) is (a) as safe and effective as warfarin in patients with acute DVT, and (b) is quite effective in preventing recurrent venous thromboembolism if taken longer-term, with an acceptable risk of bleeding (reference 1). 

Background

A number of new anticoagulants, including Xarelto®, are in development, that have several advantages over warfarin (Coumadin®, Jantoven®): (a) no need for monitoring of the anticoagulant effect; (b) no interactions with vitamin K , so no dietary restrictions; (c) full anticoagulant effect achieved within 2-4 hours of taking the drugs; (d) quick disappearance of the anticoagulant effect (within less than 36 hours) once the drug is stopped.

Study Part #1

The purpose of this first part of the study, called  EINSTEIN DVT, was to investigate, whether patients who present with actue DVT can be effectively and safely treated with Xarelto®, receiving the drug as soon as the diagnosis of acute DVT is made and getting it for up to 12 months.  This large trial enrolled 3,449 patients with newly diagnosed acute DVT.  Patients received either (a) Xarelto® from the get-go, without the need for initial s.c. injection of low molecular weight heparin (LMWH), or (b) initial injections of LMWH, followed by warfarin.  Patients were either treated for 3, 6, or 12 months with these anticoagulants, depending on how long their physicians thought they needed to be on anticoagulants.  The patients treated with Xarelto® received 15 mg twice a day for the first 3 weeks, then 20 mg once daily thereafter.  The patients on warfarin were treated to the usual target INR (International Normalized Ratio) of 2.0-3.0.  Xarelto® and warfarin were equally effective: 3 % of the patients on warfarin developed a new venous thromboembolism (VTE), versus 2.1 % of the Xarelto®-treated patients.  Meaningful bleeding (= major or clinically relevant non-major bleeding)  occurred in 8.1 % in each group.  Thus, the conclusion, that for the treatment of patients with acute DVT, Xarelto® is equally effective and safe as warfarin.

Study Part #2

The purpose of this second part of the study, called EINSTEIN DVT Extension, was to investigate whether long-term Xarelto® is effective in preventing recurrent VTE and investigate its safety.  This trial enrolled 1,196 patients who had had a DVT and had already been treated with 6 to 12 months with an anticoagulant.  Patients were then enrolled into this extension study and either treated with Xarelto® at 20 mg once daily or with placebo.  Of the patients in the placebo group, 7.1 %  developed a new VTE , whereas in the Xarelto®-treated patients only 1.3 %  developed recurrent VTE.  Significant bleeding was more common in the Xarelto®-treated patients (0.7 %)), whereas none of the placebo treated patients had a bleed.  However, this difference was statistically not significantly different.  The conclusion was Xarelto® given longer-term has a good benefit-to-risk profile.

Overall Conclusion

Xarelto® is approved in the United States for VTE  prevention after orthopedic surgery and for atrial fibrillation.   For the treatment of VTE it is not yet approved in any country.  However, the results of the 2 studies discussed here are very promising, as they show that Xarelto® is (a) as safe and effective as warfarin for the treatment of acute DVT, and (b) fairly effective and safe in the long-term prevention of recurrent VTE.  Hopefully, this will lead to FDA application for the use of Xarelto® in DVT in the next year or so.  A trial on the use of Xarelto® in PE is still ongoing (ref 2).

References

1. EINSTEIN investigators. Oral Rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-2510
2. www.clinicaltrials.gov

For patients

The same information discussed here, written for patients and non-health care providers, is available here.

Disclosures: I have consulted for OthoMcNeil and Bayer, the companies developing Xarelto® .

Last updated: Nov 4th, 2011