Rivaroxaban Cut VTE Plus Death After Hip, Knee Surgery

BERLIN — Rivaroxaban, an investigational oral anticoagulant, significantly cut the combined rate of symptomatic venous thromboembolism and death, compared with enoxaparin, in orthopedic surgery patients in an analysis of four trials involving more than 12,000 patients.

Rivaroxaban produced this and other efficacy benefits vs. enoxaparin without causing a significant increase in most bleeding measures, Dr. Sylvia Haas said at the annual congress of the European Hematology Association.

The RECORD (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials 1-4 included two studies that enrolled patients following hip surgery, and two that enrolled knee surgery patients (N. Engl. J. Med. 2008;358:2765-75; 2776-86; Lancet 2008;372:31-9; 2009;373:1673-80).

Based on the evidence in these four studies with 6,000 orthopedic surgery patients treated with rivaroxaban, the Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration voted 15-2 in favor of approving the drug for this indication. Ortho-McNeil, which is developing the drug with Bayer, later announced that the FDA sent the company additional questions about the application, but did not ask for any new studies. In countries where it has been approved, rivaroxaban has been marketed as Xarelto.

Dr. Haas, a hematologist and professor of medicine at the Technical University of Munich, said she is a consultant to Bayer Schering Pharma, and is a consultant to, or serves on data and safety monitoring boards for, other drug companies.

A direct inhibitor of coagulation factor Xa, rivaroxaban has high oral bioavailability, rapid onset of action, a 5- to 9-hour half-life, and—importantly—a predictable anticoagulant effect that, unlike warfarin, requires no monitoring.

The primary outcome of the combined analysis was the incidence of symptomatic venous thromboembolism (VTE) and all-cause death during active treatment. This occurred in 0.6% of 6,183 patients on rivaroxaban and 1.3% of 6,200 patients on enoxaparin, a 58% relative risk reduction with rivaroxaban.

Rivaroxaban was significantly better than enoxaparin on a composite of death, MI, stroke, symptomatic VTE, and major bleeds. The composite occurred 96 times in the rivaroxaban patients and 139 times among those on enoxaparin, a 31% relative risk reduction with rivaroxaban.

Although patients on rivaroxaban had more major bleeds, surgical-site bleeds, and clinically relevant nonmajor bleeds, most of these categories showed no significant difference between the rivaroxaban and enoxaparin subgroups. The only exception was the combination of major bleeds and clinically relevant nonmajor bleeds, which occurred in 2.55% of patients on enoxaparin and 3.19% of those not on the drug. (See box.)

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BERLIN — Rivaroxaban, an investigational oral anticoagulant, significantly cut the combined rate of symptomatic venous thromboembolism and death, compared with enoxaparin, in orthopedic surgery patients in an analysis of four trials involving more than 12,000 patients.

Rivaroxaban produced this and other efficacy benefits vs. enoxaparin without causing a significant increase in most bleeding measures, Dr. Sylvia Haas said at the annual congress of the European Hematology Association.

The RECORD (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials 1-4 included two studies that enrolled patients following hip surgery, and two that enrolled knee surgery patients (N. Engl. J. Med. 2008;358:2765-75; 2776-86; Lancet 2008;372:31-9; 2009;373:1673-80).

Based on the evidence in these four studies with 6,000 orthopedic surgery patients treated with rivaroxaban, the Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration voted 15-2 in favor of approving the drug for this indication. Ortho-McNeil, which is developing the drug with Bayer, later announced that the FDA sent the company additional questions about the application, but did not ask for any new studies. In countries where it has been approved, rivaroxaban has been marketed as Xarelto.

Dr. Haas, a hematologist and professor of medicine at the Technical University of Munich, said she is a consultant to Bayer Schering Pharma, and is a consultant to, or serves on data and safety monitoring boards for, other drug companies.

A direct inhibitor of coagulation factor Xa, rivaroxaban has high oral bioavailability, rapid onset of action, a 5- to 9-hour half-life, and—importantly—a predictable anticoagulant effect that, unlike warfarin, requires no monitoring.

The primary outcome of the combined analysis was the incidence of symptomatic venous thromboembolism (VTE) and all-cause death during active treatment. This occurred in 0.6% of 6,183 patients on rivaroxaban and 1.3% of 6,200 patients on enoxaparin, a 58% relative risk reduction with rivaroxaban.

Rivaroxaban was significantly better than enoxaparin on a composite of death, MI, stroke, symptomatic VTE, and major bleeds. The composite occurred 96 times in the rivaroxaban patients and 139 times among those on enoxaparin, a 31% relative risk reduction with rivaroxaban.

Although patients on rivaroxaban had more major bleeds, surgical-site bleeds, and clinically relevant nonmajor bleeds, most of these categories showed no significant difference between the rivaroxaban and enoxaparin subgroups. The only exception was the combination of major bleeds and clinically relevant nonmajor bleeds, which occurred in 2.55% of patients on enoxaparin and 3.19% of those not on the drug. (See box.)

ELSEVIER GLOBAL MEDICAL NEWS

BERLIN — Rivaroxaban, an investigational oral anticoagulant, significantly cut the combined rate of symptomatic venous thromboembolism and death, compared with enoxaparin, in orthopedic surgery patients in an analysis of four trials involving more than 12,000 patients.

Rivaroxaban produced this and other efficacy benefits vs. enoxaparin without causing a significant increase in most bleeding measures, Dr. Sylvia Haas said at the annual congress of the European Hematology Association.

The RECORD (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials 1-4 included two studies that enrolled patients following hip surgery, and two that enrolled knee surgery patients (N. Engl. J. Med. 2008;358:2765-75; 2776-86; Lancet 2008;372:31-9; 2009;373:1673-80).

Based on the evidence in these four studies with 6,000 orthopedic surgery patients treated with rivaroxaban, the Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration voted 15-2 in favor of approving the drug for this indication. Ortho-McNeil, which is developing the drug with Bayer, later announced that the FDA sent the company additional questions about the application, but did not ask for any new studies. In countries where it has been approved, rivaroxaban has been marketed as Xarelto.

Dr. Haas, a hematologist and professor of medicine at the Technical University of Munich, said she is a consultant to Bayer Schering Pharma, and is a consultant to, or serves on data and safety monitoring boards for, other drug companies.

A direct inhibitor of coagulation factor Xa, rivaroxaban has high oral bioavailability, rapid onset of action, a 5- to 9-hour half-life, and—importantly—a predictable anticoagulant effect that, unlike warfarin, requires no monitoring.

The primary outcome of the combined analysis was the incidence of symptomatic venous thromboembolism (VTE) and all-cause death during active treatment. This occurred in 0.6% of 6,183 patients on rivaroxaban and 1.3% of 6,200 patients on enoxaparin, a 58% relative risk reduction with rivaroxaban.

Rivaroxaban was significantly better than enoxaparin on a composite of death, MI, stroke, symptomatic VTE, and major bleeds. The composite occurred 96 times in the rivaroxaban patients and 139 times among those on enoxaparin, a 31% relative risk reduction with rivaroxaban.

Although patients on rivaroxaban had more major bleeds, surgical-site bleeds, and clinically relevant nonmajor bleeds, most of these categories showed no significant difference between the rivaroxaban and enoxaparin subgroups. The only exception was the combination of major bleeds and clinically relevant nonmajor bleeds, which occurred in 2.55% of patients on enoxaparin and 3.19% of those not on the drug. (See box.)

ELSEVIER GLOBAL MEDICAL NEWS