Fixed-Dose Rivaroxaban Slashes Risk of Recurrent VTE

NEW ORLEANS — Rivaroxaban, an oral anticoagulant that does not require monitoring, produced a dramatic long-term decline in recurrent venous thromboembolism in results from the EINSTEIN-Extension Study.

Patients treated with rivaroxaban had an 82% reduction in the risk of a recurrence, compared with their counterparts treated with placebo—without an increase in the risks of major bleeding or hepatotoxicity, according to a late-breaker presentation at the annual meeting of the American Society of Hematology.

Rivaroxaban has been approved in several countries, according to a statement from Bayer HealthCare, a partner in the drug's development. Despite a Food and Drug Administration advisory panel vote favoring approval in the United States, an application is on hold pending additional data.

Rivaroxaban is a direct factor Xa inhibitor, with pharmacokinetics and other characteristics that give it several advantages over vitamin K antagonists such as warfarin (Coumadin), said Dr. Harry R. Büller, a vascular medicine specialist at the Academic Medical Center in Amsterdam. Namely, this drug does not require regular laboratory monitoring, dose adjustments, or dietary restrictions.

He and his coinvestigators enrolled patients from 28 countries who had completed 6–12 months of anticoagulant therapy for a confirmed symptomatic VTE and did not have any clear indication for either continuing or discontinuing this therapy.

The patients were randomly assigned to double-blind treatment for an additional 6–12 months with a placebo or rivaroxaban at a fixed dose of 20 mg once daily. Intent-to-treat analyses were based on 602 patients assigned to rivaroxaban and 594 patients assigned to placebo. They were 58 years old on average, and 58% were male.

The mean duration of anticoagulant therapy before trial entry was about 8 months, and the mean duration of treatment on the trial was about 6 months.

Compared with their counterparts in the placebo group, patients in the rivaroxaban group were less likely to experience symptomatic recurrent VTE—the composite of recurrent deep venous thrombosis, nonfatal pulmonary embolism (PE), fatal PE, or unexplained death where PE could not be excluded (1.3% vs. 7.1%).

The difference between groups corresponded to an 82% relative reduction in risk with rivaroxaban (hazard ratio, 0.18), Dr. Büller reported. The number needed to treat to prevent one VTE event was 15.

The incidence of major bleeding was essentially the same in the two groups (0.7% with rivaroxaban and 0% with placebo). No events were fatal or located in a critical site, he noted. However, patients in the rivaroxaban group were more likely to experience clinically relevant nonmajor bleeding (for example, prolonged nosebleeds, large skin hematomas, and macroscopic hematuria): 5.4% vs. 1.2%.

In 7–8 months, the results of EINSTEIN-DVT, a head-to-head comparison between rivaroxaban and warfarin, will be available, he said.

Disclosures: Dr. Büller reported that he has received research funding from and been a consultant and advisory board member for Bayer HealthCare.

NEW ORLEANS — Rivaroxaban, an oral anticoagulant that does not require monitoring, produced a dramatic long-term decline in recurrent venous thromboembolism in results from the EINSTEIN-Extension Study.

Patients treated with rivaroxaban had an 82% reduction in the risk of a recurrence, compared with their counterparts treated with placebo—without an increase in the risks of major bleeding or hepatotoxicity, according to a late-breaker presentation at the annual meeting of the American Society of Hematology.

Rivaroxaban has been approved in several countries, according to a statement from Bayer HealthCare, a partner in the drug's development. Despite a Food and Drug Administration advisory panel vote favoring approval in the United States, an application is on hold pending additional data.

Rivaroxaban is a direct factor Xa inhibitor, with pharmacokinetics and other characteristics that give it several advantages over vitamin K antagonists such as warfarin (Coumadin), said Dr. Harry R. Büller, a vascular medicine specialist at the Academic Medical Center in Amsterdam. Namely, this drug does not require regular laboratory monitoring, dose adjustments, or dietary restrictions.

He and his coinvestigators enrolled patients from 28 countries who had completed 6–12 months of anticoagulant therapy for a confirmed symptomatic VTE and did not have any clear indication for either continuing or discontinuing this therapy.

The patients were randomly assigned to double-blind treatment for an additional 6–12 months with a placebo or rivaroxaban at a fixed dose of 20 mg once daily. Intent-to-treat analyses were based on 602 patients assigned to rivaroxaban and 594 patients assigned to placebo. They were 58 years old on average, and 58% were male.

The mean duration of anticoagulant therapy before trial entry was about 8 months, and the mean duration of treatment on the trial was about 6 months.

Compared with their counterparts in the placebo group, patients in the rivaroxaban group were less likely to experience symptomatic recurrent VTE—the composite of recurrent deep venous thrombosis, nonfatal pulmonary embolism (PE), fatal PE, or unexplained death where PE could not be excluded (1.3% vs. 7.1%).

The difference between groups corresponded to an 82% relative reduction in risk with rivaroxaban (hazard ratio, 0.18), Dr. Büller reported. The number needed to treat to prevent one VTE event was 15.

The incidence of major bleeding was essentially the same in the two groups (0.7% with rivaroxaban and 0% with placebo). No events were fatal or located in a critical site, he noted. However, patients in the rivaroxaban group were more likely to experience clinically relevant nonmajor bleeding (for example, prolonged nosebleeds, large skin hematomas, and macroscopic hematuria): 5.4% vs. 1.2%.

In 7–8 months, the results of EINSTEIN-DVT, a head-to-head comparison between rivaroxaban and warfarin, will be available, he said.

Disclosures: Dr. Büller reported that he has received research funding from and been a consultant and advisory board member for Bayer HealthCare.

NEW ORLEANS — Rivaroxaban, an oral anticoagulant that does not require monitoring, produced a dramatic long-term decline in recurrent venous thromboembolism in results from the EINSTEIN-Extension Study.

Patients treated with rivaroxaban had an 82% reduction in the risk of a recurrence, compared with their counterparts treated with placebo—without an increase in the risks of major bleeding or hepatotoxicity, according to a late-breaker presentation at the annual meeting of the American Society of Hematology.

Rivaroxaban has been approved in several countries, according to a statement from Bayer HealthCare, a partner in the drug's development. Despite a Food and Drug Administration advisory panel vote favoring approval in the United States, an application is on hold pending additional data.

Rivaroxaban is a direct factor Xa inhibitor, with pharmacokinetics and other characteristics that give it several advantages over vitamin K antagonists such as warfarin (Coumadin), said Dr. Harry R. Büller, a vascular medicine specialist at the Academic Medical Center in Amsterdam. Namely, this drug does not require regular laboratory monitoring, dose adjustments, or dietary restrictions.

He and his coinvestigators enrolled patients from 28 countries who had completed 6–12 months of anticoagulant therapy for a confirmed symptomatic VTE and did not have any clear indication for either continuing or discontinuing this therapy.

The patients were randomly assigned to double-blind treatment for an additional 6–12 months with a placebo or rivaroxaban at a fixed dose of 20 mg once daily. Intent-to-treat analyses were based on 602 patients assigned to rivaroxaban and 594 patients assigned to placebo. They were 58 years old on average, and 58% were male.

The mean duration of anticoagulant therapy before trial entry was about 8 months, and the mean duration of treatment on the trial was about 6 months.

Compared with their counterparts in the placebo group, patients in the rivaroxaban group were less likely to experience symptomatic recurrent VTE—the composite of recurrent deep venous thrombosis, nonfatal pulmonary embolism (PE), fatal PE, or unexplained death where PE could not be excluded (1.3% vs. 7.1%).

The difference between groups corresponded to an 82% relative reduction in risk with rivaroxaban (hazard ratio, 0.18), Dr. Büller reported. The number needed to treat to prevent one VTE event was 15.

The incidence of major bleeding was essentially the same in the two groups (0.7% with rivaroxaban and 0% with placebo). No events were fatal or located in a critical site, he noted. However, patients in the rivaroxaban group were more likely to experience clinically relevant nonmajor bleeding (for example, prolonged nosebleeds, large skin hematomas, and macroscopic hematuria): 5.4% vs. 1.2%.

In 7–8 months, the results of EINSTEIN-DVT, a head-to-head comparison between rivaroxaban and warfarin, will be available, he said.

Disclosures: Dr. Büller reported that he has received research funding from and been a consultant and advisory board member for Bayer HealthCare.