The Phase III EINSTEIN-DVT clinical trial of the oral anticoagulant Rivaroxaban ( Xarelto ) demonstrated non-inferiority compared to the standard of care for the prevention of recurrent venous thromboembolism ( VTE ) in patients with acute symptomatic deep vein thrombosis ( DVT ), with a comparable safety profile.

In the study, oral Rivaroxaban demonstrated non-inferiority for the primary efficacy outcome, defined as the cumulative incidence of symptomatic recurrent deep vein thrombosis and non-fatal or fatal pulmonary embolism, in patients with acute symptomatic deep vein thrombosis compared with the current standard of care of Enoxaparin ( Lovenox ) followed by a vitamin K antagonist ( VKA ) ( 2.1% vs 3%, respectively; p <0.0001 for non-inferiority ).

Rivaroxaban also demonstrated similar results compared to the standard of care for the principal safety outcome measuring a composite of major and non-major clinically relevant bleeding events ( 8.1% in both treatment groups; p=0.77 ).
Monthly liver function tests did not reveal a signal for impaired liver safety. Rivaroxaban was well tolerated in the study, and discontinuation rates related to adverse events were low and similar in both treatment groups.

Net clinical benefit, a pre-specified secondary outcome defined as the composite of the primary efficacy outcome plus major bleeding, demonstrated an improvement for Rivaroxaban compared to standard therapy ( 2.9% vs 4.2%, respectively; HR of 0.67 ). Other presented secondary outcomes, including all-cause mortality ( 2.2% vs 2.9%, respectively; HR of 0.67 ) and cardiovascular events ( 0.7% vs 0.8%, respectively; HR of 0.79 ) were not statistically significantly different.

EINSTEIN is a global clinical development program composed of three clinical studies in nearly 9,000 patients: EINSTEIN-DVT, EINSTEIN-PE and EINSTEIN-Extension. Two of these studies enrolled patients with acute, symptomatic deep vein thrombosis ( EINSTEIN-DVT ) or pulmonary embolism ( EINSTEIN-PE ). In these two trials, patients received oral Rivaroxaban 15 mg twice-daily for the first three weeks, followed by oral Rivaroxaban 20 mg once-daily, compared with initial Enoxaparin treatment followed by a vitamin K antagonist.

Source: European Society of Cardiology Congress, 2010

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