Interpretation of Benefit-Risk of Enoxaparin as Comparator in the RECORD Program: Rivaroxaban Oral Tablets (10 milligrams) for Use in Prophylaxis in Deep Vein Thrombosis and Pulmonary Embolism in Patients Undergoing Hip or Knee Replacement Surgery

Abstract

The Regulation of Coagulation in Major Orthopedic surgery reducing the Risk of DVT and PE (RECORD) clinical program of rivaroxaban consists of 4 phase III clinical trials comparing rivaroxaban with enoxaparin for the prevention of venous thromboembolism (VTE) in patients undergoing either total hip or total knee replacement surgery. Despite the comprehensive and extensive nature of this program, it had some logistic issues that included the dosing of the enoxaparin which was not only inconsistent with the recommendations but the dosages used were not optimal. The duration of treatment while consistent with rivaroxaban did vary with enoxaparin and was somewhat short. The bleeding definitions and safety evaluations were not consistent in accordance with the current recommendations. Moreover, the RECORD program has no power to show differences in major bleeding. The cardiovascular rebound phenomenon should have been adequately addressed and may require additional clinical validation to establish the safety of rivaroxaban. Although the US Food and Drug Administration (FDA) advisory committee has recommended approval of rivaroxaban, the reported analysis strongly suggests additional clinical validation on the claimed benefit/risk ratio of this monotherapeutic anticoagulant.

Thromboprophylaxis with dabigatran etexilate in patients over seventy-five years of age with moderate renal impairment undergoing or knee replacement

“…Furthermore, a recent international clinical guideline committee noted that renal function should be considered and that lower than standard doses of anticoagulant therapy should be prescribed [7]. This view is supported by a recent comment by van Thiel et al that additional studies with lower drug doses be undertaken if there is concern over bleeding with new antithrombotic agents [28].…”

New oral anticoagulants: a practical guide for clinicians

“…Despite some inconsistencies between trials, no differences in any category of bleeding were found between ribaroxaban and enoxaparin in any of the trials. However, concerns have been raised about the risk/benefit ratio of rivaroxaban versus enoxaparin based on the manner in which bleeding complications were defined and reported in these trials and were among the concerns leading the FDA to postpone approval pending further information from the manufacturer [17]. The single apixaban trial used the accepted definitions of major and clinically relevant non-major bleeding.…”

Use of Rivaroxaban for Prophylaxis of Superficial Venous Thrombosis in Klippel-Trenaunay-Weber Syndrome

“…10 Thirdly, prophylactic rivaroxaban (10 mg daily) has been shown to be effective and safe as a DVT prophylactic regimen in the those undergoing major orthopedic surgery. 11 Finally, prophylactic dose anticoagulation has been shown to be effective in the treatment of SVT. 9 In conclusion, KTWS is a rare condition that can be complicated by a variety of thrombotic manifestations.…”