Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Rivaroxaban or Aspirin for Extended VTE Treatment?

N Engl J Med; ePub 2017 Mar 18; Weitz, et al

Among patients with venous thromboembolism (VTE) who required extended treatment, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose or a prophylactic dose when compared with aspirin, a recent study found. This randomized, double-blind, phase 3 study assigned 3,396 patients with VTE to receive either once-daily rivaroxaban (doses of 20 mg or 10 mg) or 100 mg of aspirin (median treatment duration, 351 days). Primary efficacy outcome was symptomatic recurrent fatal or nonfatal VTE. Researchers found:

  • Primary efficacy outcome occurred in 17 of 1,107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1,127 patients (1.2%) receiving 10 mg rivaroxaban vs 50 of 1,131 patients (4.4%) receiving aspirin.
  • There was no significant increase in bleeding rates in the rivaroxaban arms.
  • Incidence of adverse events was similar in all 3 groups.


Weitz JI, Lensing AWA, Prins MH, et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. [Published online ahead of print March 18, 2017]. N Engl J Med. doi:10.1056/NEJMoa1700518.


Patients without a reversible risk factor for VTE who have a single episode of DVT or PE have a recurrence rate of approximately 35% over the subsequent 5 years, with that rate of recurrence being greatest in the first 1 to 2 years after the initial VTE. For this reason, current guidelines suggest consideration of long-term anticoagulation to decrease the risk of recurrence after a first unprovoked episode of VTE.1 Previously, dabigatran, one of the non-vitamin K oral anticoagulants (NOACs), was shown to be effective in the extended treatment of venous thromboembolism, decreasing recurrence by 92% with a lower risk of major bleeding than warfarin, but still with a higher risk of bleeding than placebo.2 Many clinicians are not comfortable with the idea of long-term anticoagulation for this decreasing recurrence of VTE due to the bleeding risk associated with anticoagulation, and clinicians often either stop treatment after 3 months, or risk stratify (D-dimer testing 1 month after anticoagulation is stopped, ultra-sound looking for resolution of the DVT, with males having about twice the recurrence rate of females) in order to determine which patients are at higher risk and have a better risk/benefit profile for long-term anticoagulation. Since studies have shown aspirin to decrease the risk of VTE recurrence by about 30%, aspirin is sometimes used to decrease the risk of recurrence when anticoagulation is not used.3 This study shows that rivaroxaban at a dose of either 10 mg or 20 mg has no greater bleeding risk than aspirin, but far greater efficacy, with the 10 mg dose reducing the 1 year risk of recurrence by 74% compared to aspirin. This level of safety, along with the high efficacy, radically shifts the risk/benefit ratio in greater favor of benefit for long-term prophylaxis of VTE. —Neil Skolnik, MD

  1. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149:315-52.
  2. Schulman S, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013; 368:709-718. doi:10.1056/NEJMoa1113697.
  3. Brighton TA, Eikelboom JW, Mann K, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367:1979-87.