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Proven Efficacy Profile in DVT, PE, and Risk Reduction

XARELTO® was evaluated as a single, oral agent in three phase 3 clinical trials including more than 9400 patients. XARELTO® showed proven efficacy for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and as extended treatment to reduce risk of recurrence of DVT and PE. Efficacy was also shown in a pooled subgroup analysis of DVT and PE patients.1

Patient Population Studied in the EINSTEIN–DVT and EINSTEIN–PE Clinical Trials

ROCKET AF studied Xarelto in patients with prior stroke or multiple comorbidities

At least as effective as standard of care (enoxaparin + warfarin) in DVT

XARELTO® efficacy is noninferior to standard of care in treating DVT XARELTO® efficacy is noninferior to standard of care in treating DVT
  • Patients were randomized on either XARELTO® alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) or enoxaparin 1 mg/kg twice daily for at least 5 days with a vitamin K antagonist (VKA) and then continued with VKA only after target INR (2.0-3.0) was reached.

  • The efficacy of XARELTO® was generally consistent across major subgroups (age, weight, gender, CrCl, intended treatment duration)2,6

  • Patients with DVT were treated for 3, 6, or 12 months at physicians' discretion2

    • The mean duration of treatment was approximately 6 months1

The mean duration of treatment was 194 days for patients treated with XARELTO® and 188 days for patients treated with enoxaparin/warfarin.1

At least as effective as standard of care (enoxaparin + warfarin) in PE

XARELTO® efficacy is noninferior to standard of care in treating PE XARELTO® efficacy is noninferior to standard of care in treating PE
  • Patients were randomized on either XARELTO® alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) or enoxaparin 1 mg/kg twice daily for at least 5 days with a vitamin K antagonist (VKA) and then continued with VKA only after target INR (2.0-3.0) was reached

  • The efficacy of XARELTO® was generally consistent across major subgroups (age, weight, gender, CrCl, intended treatment duration)3,7

  • Patients with PE were treated for 3, 6, or 12 months at physicians' discretion3

    • The mean duration of treatment was approximately 7 months||

||The mean duration of treatment was 216 days for patients treated with XARELTO® and 214 days for patients treated with enoxaparin/warfarin.1

Pooled subgroup analysis of the EINSTEIN–DVT and –PE randomized trials

XARELTO® shown to be noninferior in regard to recurrent VTE (primary efficacy outcome), in a pooled subanalysis of all patients and patients with cancer, a previous DVT/PE, and those designated as fragile XARELTO® shown to be noninferior in regard to recurrent VTE (primary efficacy outcome), in a pooled subanalysis of all patients and patients with cancer, a previous DVT/PE, and those designated as fragile

A pooled analysis of the efficacy data of both trials was conducted, including key prespecified subgroups, such as fragile patients, those with cancer, and those with previous VTE. Both studies used identical designs, treatment regimens, outcome definitions, and adjudication processes to facilitate pooled analyses.1,4

Fragility was defined as one or more of these criteria: age >75 years, CrCl <50 mL/min, or body weight ≤50 kg.1

Extended treatment proven to reduce risk of recurrence

Does the risk persist?

Rate of Recurrent  DVT and PE in Provoked and Unprovoked patients Rate of Recurrent  DVT and PE in Provoked and Unprovoked patients
Nearly 1 in 3 patients with unprovoked VTE have a recurrence within 5 years of stopping anticoagulation therapy.8

VTE risk continues after treatment concludes.**

Continuing XARELTO® therapy for extended risk reduction‡‡

Chart shows a proven risk reduction for longer-term treatment for reducing the risk of recurrence of DVT and PE with Xarelto Chart shows a proven risk reduction for longer-term treatment for reducing the risk of recurrence of DVT and PE with Xarelto

EINSTEIN–EXT, a randomized, double-blind, event-driven, superiority trial, was part of the largest DVT and PE phase 3 clinical trial program ever conducted (N=9477).§§

  • All patients had already undergone 6 to 14 months|||| of anticoagulation therapy and were at clinical equipoise with respect to the need for continued anticoagulation2

  • Patients were randomized on either XARELTO® 20 mg once daily or placebo

  • Patients on placebo had a significantly greater rate of recurrent VTE than patients on XARELTO® (42 events vs 8 events, HR [95% CI]: 0.18 [0.09-0.39], P<0.0001)

  • Average duration of treatment was 190 days for both arms

**VTE treatment guidelines suggest ongoing treatment could begin any time after 3 months of initial treatment.8,9

‡‡Longer than 6 months.

§§Composed of the EINSTEIN–DVT (N=3449), EINSTEIN–PE (N=4832), and EINSTEIN–EXT (N=1196) trials.

||||Although the EINSTEIN–EXT trial was designed to evaluate patients who had previously completed 6 to 12 months of treatment with either rivaroxaban or warfarin before trial enrollment, some of the patients could have received up to 14 months of anticoagulation treatment before enrollment.2

CrCl = creatinine clearance.

 

Indications

 

IMPORTANT SAFETY INFORMATION

 

Indication and Important saftey Information

 

  • Reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). There are limited data on the relative effectiveness of XARELTO® (rivaroxaban) and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well controlled.
  • Treatment of deep vein thrombosis (DVT).
  • Treatment of pulmonary embolism (PE).
  • Reduction in the risk of recurrence of DVT and of PE following initial 6 months treatment for DVT and/or PE.
  • Prophylaxis of DVT, which may lead to PE in patients undergoing knee replacement surgery.
  • Prophylaxis of DVT, which may lead to PE in patients undergoing hip replacement surgery.

References:

  1. Prins MH, Lensing AWA, Bauersachs R, et al, on behalf of the EINSTEIN Investigators. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013;11(1):21.
  2. The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499-2510.
  3. The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-1297.
  4. Prins MH, Lensing AWA, Brighton TA, et al. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomized controlled trials. Lancet Haematol. 2014;1(1):e37-e46.
  5. Data on file. Janssen Pharmaceuticals, Inc.
  6. Online supplement to: The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499-2510. http://www.nejm.org/doi/suppl/10.1056/NEJMoa1007903/suppl_file/nejmoa1007903_appendix.pdf. Accessed May 5, 2016.
  7. Online supplement to: The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-1297. http://www.nejm.org/doi/suppl/10.1056/NEJMoa1113572/suppl_file/nejmoa1113572_appendix.pdf. Accessed May 5, 2016.
  8. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e419S-e494S.
  9. Snow V, Qaseem A, Barry P, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146(3):204-210.