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Two clinical trials compared rivaroxaban vs enoxaparin prophylactic treatment to prevent venous thromboembolism (VTE) after total hip or knee arthroplasty.

Better VTE Prophylaxis

September 1, 2008

Better VTE Prophylaxis

Abstract & Commentary

By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.

Synopsis: Rivaroxaban is more effective for venous thrombosis prophylaxis than low-molecular-weight heparin.

Source: Eriksson BI, et al. Rivaroxaban versus enoxaparin for thrombophrophylaxis after hip arthroplasty. NEJM. 2008;358:2765-2775.

Two clinical trials compared rivaroxaban vs enoxaparin prophylactic treatment to prevent venous thromboembolism (VTE) after total hip or knee arthroplasty. The doses were 10 mg daily for rivaroxaban given orally, and 40 mg daily for enoxaparin, which is a low-molecular-weight heparin and is administered subcutaneously. In a multicenter phase 3 trial with 4541 patients undergoing hip arthroplasty, deep-vein thrombosis occurred about 3 times more frequently with enoxaparin compared with rivaoxaban.1 There were 4 major cases of VTE in the rivaroxaban group and 33 in the enoxaparin group. Bleeding problems occurred at a similar rate in both groups, about 3%. In the second trial, 2531 patients underwent knee arthroplasty, with a similar treatment regimen comparing the two drugs.2 Rivaroxaban was again superior to enoxaparin, a 9.6% incidence of VTE compared with 18.9%. And again, bleeding rates, about 0.5%, were similar.

Commentary

The clinical and economic importance of venous thromboembolism (VTE) is easy to overlook. But, it is the third leading cause of cardiovascular death in the U.S., after myocardial infarction and stroke, with about 2 million cases of deep vein thrombosis recorded annually. Despite the demonstrated efficacy of VTE prophylaxis, it is highly underutilized. This has prompted the incorporation of VTE prophylaxis as a measurement of institutional performance and reimbursement. Because of the high prevalence of VTE after arthroplasty procedures, orthopedics has been leading the way in developing pharmacologic options for prophylaxis.

It is standard orthopedic procedure to provide prophylactic anticoagulant therapy for 5 weeks after total hip or knee arthroplasty. The available options with their drawbacks are low-molecular-weight heparin (requires subcutaneous administration) and vitamin K antagonists such as warfarin (requires frequent monitoring and has numerous food and drug interactions). Rivaroxaban is given orally and directly inhibits activated factor X (factor Xa). Low-molecular weight heparin also inhibits factor Xa, but inhibits factor IIa as well.

There is a concern that cardiovascular events might be precipitated after discontinuing anticoagulation treatment because an acute reactivation of coagulation. In the hip arthroplasty trial, 8 events occurred in the rivaroxaban group and 1 in the enoxaparin group, but the results were reversed in the knee arthroplasty trial, with no event in the rivaroxaban group and 7 in the enoxaparin group. This issue remains unresolved.

Although VTE does not occur after gynecologic procedures at the same rates observed with hip or knee arthroplasty, it is not uncommon to encounter situations where thrombosis prophylaxis is indicated. These two clinical trials unequivocally demonstrate the superiority of rivaoxaban, not only in terms of efficacy but in the ease of its oral administration.

What about aspirin? The American Academy of Orthopaedic Surgeons lists aspirin as an appropriate choice for standard risk patients, but not for patients at elevated risk. In a meta-analysis of randomized trials involving hip replacement (published by my brother), aspirin was not effective in preventing VTE. 3 Although, sufficiently powered clinical trials comparing aspirin to the other treatment options have not been conducted, it seems reasonable to conclude that aspirin is not the treatment of choice for prophylaxis, being surpassed in efficacy by low-molecular-weight heparin and now rivaoxaban. An international consensus advised against aspirin monotherapy for the prevention of VTE.4

Pharmacologic prophylaxis should be considered for all hospitalized acutely ill patients, and for patients undergoing major surgical procedures, especially those at higher risk for VTE. Extended post-discharge prophylaxis is indicated for reduced mobility and for high risk patients (such as older patients with cancer or a history of VTE). The greater impact of rivaoxaban is impressive; at the present time, because of the greater efficacy and the ease of oral administration, this may be the drug of choice. There are other potential uses for this drug that remain to be studied. One such use would be its prophylactic use in a postmenopausal woman who desires estrogen therapy and tests positively for an inherited clotting disorder.

References

  1. Eriksson BI, et al. Rivaroxaban versus enoxaparin for thrombophrophylaxis after hip arthroplasty. NEJM. 2008;358:2765-2775.
  2. Lassen MR, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. NEJM. 2008;358:2776-2786.
  3. Imperiale TF, Speroff T. A meta-analysis of methods to prevent venous thromboembolism following total hip replacement. JAMA. 1994;271:1780-1785.
  4. Cardiovascular Disease Educational and Research Trust, Cyprus Cardiovascular Disease Educational and Research Trust, European Venous Forum, International Surgical Thrombosis Forum, International Union of Angiology, Phlebologie UID. Prevention and treatment of venous thromboembolism. International consensus statement (guidelines according to scientific evidence). Int J Angiol.2006;25:101-161.