Is There Clinical Benefit to >3 Month Rivaroxaban Tx for Unprovoked VTE?

Two studies presented at CHEST 2016 revealed that rivaroxaban lowered the risk of venous thromboembolism without increasing risk of major bleeding.

Patients who receive continuous rivaroxaban treatment for longer than 3 months had lower risk of venous thromboembolism (VTE) recurrence without an increased risk of major bleeding, compared to patients who received only 3 months of treatment, according to 2 studies1,2 presented at the CHEST 2016 Annual Meeting in Los Angeles.

The first study, led by Scott Kaatz, DO, MSc, chief quality officer of Hurley Medical Center in Flint, Michigan, researchers examined 4814 patients who began taking rivaroxaban within 7 days after an “unprovoked” VTE.1 Unprovoked VTE was defined as not having recent surgery, cancer, pregnancy, or estrogen therapy. The researchers formed 2 cohorts: the continued rivaroxaban group (n=3763) and the discontinued rivaroxaban group (n=1051).

The patients in the continued treatment group had significantly lower rates of VTE recurrences at 3 months (0.57% vs 1.19%), 6 months (1.07% vs 2.10%), and 12 months (1.45% vs 2.60%; all log-rank test P <.05). In addition, there were no statistically significant differences between the continued and discontinued cohorts in cumulative event rates for major bleeding at each time point (3 months: 0.51% vs 0.72%, 6 months: 0.79% vs 0.72%, and 12 months: 1.06% vs 1.13%; all P >.05).

In the second study, led by W. Frank Peacock, MD, of Baylor College of Medicine in Houston, Texas, researchers conducted a post-marketing surveillance study to evaluate major bleeding in patients with VTE treated with rivaroxban to determine potential risk factors for bleeding.2 They identified more than 9000 patients with VTE (n=9638) who were on rivararoxaban (43.7% with pulmonary embolism [PE] with or without deep vein thrombosis [DVT] and 56.3% with DVT without PE). A total of 130 VTE patients had major bleeding—56.9% with DVT and 43.1% with PE.

The overall cohort had an incidence rate of major bleeding of 2.47 (95% confidence interval [CI], 2.08-2.93) per 100 person-years, with a higher incidence in the DVT cohort vs the PE cohort (2.74 and 2.18 per 100-years, respectively).

Sex, dementia, anemia, and a history of bleeding were determined to be covariates significantly associated with major bleeding in multivariate analyses. Female sex had an adjusted hazard ratio (HR) of 1.70 (95% CI, 1.11-2.29), dementia had an adjusted HR of 2.01 (95% CI, 1.30-3.12), anemia had an adjusted HR of 2.57 (95% CI, 1.77-3.73), and a history of bleeding had an adjusted HR of 2.73 (95% CI, 1.41-5.26). The overall cohort had a fatal bleed rate of 0.06 (95% CI, 0.02-0.18) per 100 person-years.

“We have been closely examining the use of rivaroxaban in daily clinical practice for more than 3 years in people with non-valvular atrial fibrillation and are please to expand our work to those with VTE,” W. Frank Peacock, MD, said in a press release.3

The researchers concluded that pinpointing the risk factors for major bleeding—being female, older, and having more comorbidities—may be useful to clinicians who treat these patients.

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Disclosures: Drs Berger, Seheult, Lailberte, Crivera, Lejeune, Xiao, Schein, Lefebvre, and Kaatz have received fees from or are employees of Janssen Scientific Affairs.  Drs Peacock, Patel, and Yuan have also received various fees from Janssen. Other authors reported financial relationships with Bayer and Health Research Tx. 


  1. Berger JS, Seheult R, Laliberte F, et al. Risk of recurrences in patients with unprovoked venous thromboemolism who continued vs discontinued rivaroxaban therapy after 3-month therapy. Presented at CHEST 2016. October 22-26, 2016; Los Angeles, CA.
  2. Peacock WF, Tamayo S, Patel M, Sicignano N, Hopf KP, Yuan Z. Major bleeding in patients taking rivaroxaban for venous thromboembolism treatment. Presented at CHEST 2016. October 22-26, 2016; Los Angeles, CA.
  3. Two new real-world studies confirm positive efficacy and safety profile of Xarelto (rivaroxaban) in treating and preventing blood clots [press release]. Titusville, NJ: Johnson & Johnson Media Center; October 23, 2016. Accessed October 27, 2016.