深部静脈血栓症に対する魅力的な代替療法

EINSTEIN-DVT：経口rivaroxabanは有症状の深部静脈血栓症に対する通常の治療と比較し有効性は同等であるが管理しやすい

EINSTEIN-DVT: Oral rivaroxaban similar efficacy to usual care for treatment of symptomatic deep vein thrombosis but easier to manage

有症状の急性深部静脈血栓（DVT）に対する治療として経口Xa阻害薬である経口抗凝固薬rivaroxabanの標準的な治療（エノキサパリン後にワルファリンまたはacenocoumarol投与）に対する非劣性が認められたとのphase III EINSTEIN-DVTスタディの結果が、2010年European Society of Cardiology学会のホットラインセッションで発表された。この多国籍無作為化オープンラベル非劣性EINSTEIN-DVTスタディでは、肺塞栓の症状はないが有症状の急性DVT患者3,400人以上を組み入れた。患者は経口rivaroxaban（15mg 1日2回を3週間の後20mg 1日1回）または体重で補正したエノキサパリン皮下投与の後にワルファリンまたはacenocoumarol（治療域を維持するため用量調節）をベースライン時の主治医の評価に基づき3、6、または12ヵ月間投与された。症候性の静脈血栓塞栓再発（DVT再発、非致死性または致死性肺塞栓の合計）はrivaroxaban投与群で2.1%に発現したのに対し、標準療法を受けた患者群では3.0%であった（P<0.0001で非劣性）。EINSTEIN-DVTスタディにより、主要な安全性に関する予後である重大なまたは臨床的に明らかな重大ではない出血の発現率がrivaroxabanにおいて標準治療と比較し同等であることも示された（それぞれ8.1%対8.1%）。

Results of the Phase III EINSTEIN-DVT study show that the oral anticoagulant rivaroxaban achieved the primary efficacy and safety outcomes in the treatment of patients with acute, symptomatic deep vein thrombosis (DVT). The Phase study was presented during a Hotline session at the European Society of Cardiology Congress 2010.

The study showed that rivaroxaban demonstrated non-inferior efficacy in the treatment of DVT compared with initial enoxaparin treatment followed by a vitamin K antagonist (VKA), the current standard therapy for the treatment of DVT. Recurrent symptomatic venous thromboembolism (i.e., the composite of recurrent DVT, non-fatal or fatal pulmonary embolism) occurred in 2.1% of the rivaroxaban recipients and 3.0% of the subjects receiving standard therapy (p<0.0001 for non-inferiority).

The EINSTEIN-DVT study also demonstrated similar rates of major and clinically relevant non-major bleeding, the principal safety outcome, for rivaroxaban compared with the current standard therapy (8.1% vs. 8.1%, respectively). No liver signal attributable to rivaroxaban was observed in the study.

"The results of the EINSTEIN-DVT trial indicate that rivaroxaban is an effective and safe treatment for acute symptomatic DVT," said principal investigator, Professor Harry R. Buller, Academic Medical Center, Amsterdam, the Netherlands. "The single-drug approach with rivaroxaban will provide clinicians and patients with an attractive, simple, alternative regimen for the initial and long-term treatment of deep vein thrombosis."

The multinational EINSTEIN-DVT study was designed to investigate a new single-drug approach with rivaroxaban in comparison to standard therapy in a randomized, open-label, non-inferiority study. The trial involved more than 3,400 patients with acute symptomatic DVT, but without any symptoms of pulmonary embolism, across 253 sites in 32 countries worldwide. Patients received either oral rivaroxaban (15 mg twice-daily for the first three weeks, followed by 20 mg once daily) or body weight-adjusted subcutaneous enoxaparin followed by warfarin or acenocoumarol (dose adjusted to maintain a therapeutic normalized ratio) for three, six or 12 months, based on the attending physician's assessment at baseline.

The primary efficacy outcome was the cumulative incidence of symptomatic recurrent venous thromboembolism (non-fatal or fatal). The principal safety outcome was the composite of major and clinically relevant non-major bleeding.

The EINSTEIN-DVT trial was also considered an important study, mainly because the oral factor Xa inhibitor rivaroxaban removes many of the drawbacks associated with standard therapy (subcutaneous injections, warfarin) for the treatment of deep vein thrombosis.

The EINSTEIN DVT study was sponsored by Bayer Schering Pharma.