Xarelto® – Good News

Summary

Good news. A major study published in December 2010 in the prestigious 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 deep vein thrombosis (DVT), and (b) is quite effective in preventing recurrent blood clots (DVT and pulmonary embolism=PE) if taken longer-term, with an acceptable risk of bleeding (reference 1). The drug is NOT approved for DVT and PE treatment by the FDA. However, it was approved on July 1st, 2011 for DVT prevention after hip and knee replacement, and for atrial fibrillation (irregular heart beat) on Nov 4th, 2011.

Background

A number of new oral blood thinners, including Xarelto®, are in development, that have several advantages over warfarin (Coumadin®, Jantoven®): (a) no need for monitoring of the blood thinning effect; (b) no interactions with vitamin K , so no dietary restrictions; (c) full blood thinning effect achieved within 2-4 hours of taking the drugs; (d) quick disappearance of the blood thinning effect (within less than 36 hours) if the drug is stopped. This has also recently been discussed in the Clot Connect blog written about Pradaxa.

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 immediately when the diagnosis of acute DVT is made and getting it for up to 12 months. Thisvery 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 injection underneath the skin of low molecular weight heparin, or (b) initial injections of low molecular weight heparin, followed by warfarin. Patients were either treated for 3, 6, or 12 months with these “blood thinners”, depending on how long their physicians thought they needed to be treated with “blood thinners”. 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 blood clot (i.e. 1 out of 33 patients), versus 2.1 % of the Xarelto®-treated patients (i.e. 1 out of 48 patients). As expected when being treated with a blood thinner, a number of patients had significant bleeding (8.1 % in each group, i.e. 1 out of 12 patients); however, this was equally common in both groups. 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 further clots and whether it is safe. This trial studied 1,196 patients who had had a DVT and had already been treated with 6 to 12 months with a “blood thinner”.  Patients were then enrolled into this extension study and either treated with Xarelto® at 20 mg once daily or with no anticoagulant, receiving placebo. Of the patients who did not receive a blood thinner (the placebo group) 7.1 %  developed a new blood clot (i.e. 1 out of every 14 patients), whereas in the Xarelto®-treated patients only 1.3 % developed a new clot (i.e. 1 out of every 77 patients). Bleeding was more common in the Xarelto®-treated patients (0.7 % had a bleed, i.e. 1 out 143 patients), whereas none of the placebo treated patients had a bleed. However, this was statistically not significantly different. The conclusion was that the risk/benefit of staying on longer-term Xarelto compared to stopping “blood thinners” favors continued treatment with Xarelto®.

Conclusion

Xarelto® is approved  for DVT prevention after orthopedic surgery and for artial fibrillation.  For the treatment of DVT and PE 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 additional (recurrent) DVTs and PEs in patients who have had a clot before.  Hopefully, this will lead to FDA application and approval for the use of Xarelto® in DVT in the next year or so. A trial on the use of Xarelto® in pulmonary embolism (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

Support Forum:  Questions or comments about Xarelto? Go to the online Clot Connect Support Forum, category “Anticoagulants (blood thinners)”

For health care professionals

The same information discussed here, written for health care providers, is available here.

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

Last updated: Nov 4th, 2011