Safety and Efficacy of Prolonged Rivaroxaban to Prevent Recurrent Venous Thromboembolism

Woman with varicose veins on a leg walking using trekking poles

By Martina M. McGrath, MD
March 30, 2017

Venous thromboembolism (VTE) remains an important cause of vascular death.1 Treatment options have greatly expanded in recent years with the introduction of Wektnovel oral anticoagulants including apixaban, rivaroxaban and dabigatran and several large clinical trials have demonstrated similar efficacy and safety to warfarin in the initial treatment of VTE.2

An important question remains—how do we manage these patients after the initial three- to six-month course of anticoagulation? Patients with unprovoked VTE are estimated to have recurrence rates of up to 30% at five years, and prolonged anticoagulation can reduce this risk substantially.2  Patients who are likely to benefit include those with unprovoked proximal DVT or pulmonary embolism, those with recurrent unprovoked VTE, and possibly those with active malignancy and VTE.

A large industry-funded clinical trial published in NEJM has examined the benefit of two dosing regimens of rivaroxaban versus aspirin on the risk of recurrent VTE after initial treatment period.3 Over 3300 patients with provoked (60%) and unprovoked  (40%) VTE, who had completed 6 to 12 months of anticoagulation and had equipoise regarding the need for ongoing anticoagulation, were enrolled. Patients with an absolute indication to continue were excluded. Enrollees were randomized to receive either rivaroxaban 20 mg, 10 mg, or aspirin 100 mg, and were followed for one year post randomization.

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Recurrent VTE occurred in 1.5% and 1.2% of patients treated with 20 mg and 10 mg of rivaroxaban respectively, compared to 4.4% of aspirin-treated patients. Fatal VTE events were similar across all treatment arms. Compared to aspirin, treatment with either dose of rivaroxaban was associated with up to a 70% decrease in the risk of recurrent VTE at 12 months. Major bleeding complications were rare and similar between all groups as were nonmajor bleeding events.  The number needed to treat with rivaroxaban to prevent one recurrent VTE at one year was 33 patients.

As pointed out by the authors, the study was not powered to examine for a difference in efficacy between patients treated with 20 mg vs 10 mg of rivaroxaban.3 Similarly, those with a strong indication for long-term anticoagulation were excluded, and it is unknown if reduced intensity anticoagulation is safe and effective for such patients. However, for patients at risk of recurrent VTE, this study provides high-quality evidence that prolonged rivaroxaban treatment is very effective, and associated with an acceptable bleeding risk.

References:

  1. Centers for Disease C, Prevention. Venous thromboembolism in adult hospitalizations – United States, 2007-2009. MMWR Morbidity and mortality weekly report 2012;61:401-4.
  2. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016;149:315-52.
  3. Weitz JI, Lensing AW, Prins MH, et al. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. The New England journal of medicine 2017.

Headshot of Dr. McGrathDr. Martina McGrath is an Instructor in Medicine at Harvard Medical School, and a member of the Renal Division, Department of Medicine, at Brigham and Women’s Hospital, both in Boston. Dr. McGrath is the Medical Editor for the Trends in Medicine blog.

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