The novel oral anticoagulant rivaroxaban 20 mg once-daily significantly reduced the risk of recurrent symptomatic venous thromboembolism (VTE) compared to placebo in patients who have been treated for a previous deep vein thrombosis (DVT) or pulmonary embolism (PE). The rate of major bleeding was low. The results of the phase-III Einstein-Extension (EXT) clinical study were presented in the official press programme of the 51st Annual Meeting of the American Society of Haematology (ASH) in New Orleans, Louisiana.
Rivaroxaban showed an 82% relative risk reduction (RRR) in the recurrence of symptomatic VTE over patients treated with placebo [1.3% (n=8) vs. 7.1% (n=42), respectively] – an outcome that was highly statistically significant (p<0.0001).
“The results from Einstein-EXT highlight the potential clinical benefit of extending prophylaxis for an additional six or 12 months beyond the currently recommended treatment duration,” said Harry R Büller, Academic Medical Center in Amsterdam, Netherlands. “This study could help transform the way physicians treat patients who have previously suffered a DVT or PE. Currently, up to 10 per cent of patients who are treated adequately, according to the recommended guidelines, still experience a recurrence within 12 months of the initial event.”
In the study, rivaroxaban was well tolerated and the rates of major bleeding, the primary safety endpoint, were low and not statistically significantly different (p=0.11) between the two groups [0.7% (n=4) vs. 0.0% (n=0), for the rivaroxaban and placebo arms, respectively]. A secondary endpoint measuring the composite of major and clinically relevant, but non-major bleeding, showed a statistically significant difference (p<0.001) between the two groups [6.0% (n=36) vs. 1.2% (n=7) in the rivaroxaban and placebo arms, respectively]. Liver safety results included: ALT >3x ULN: 1.9% in the rivaroxaban arm and 0.5% of patients in the placebo arm; ALT >3x ULN + Total Bilirubin >2x ULN: n=0 in both groups. No cases of serious liver injury were reported in either group. There were no differences in the incidence of cardiovascular-related events between the two treatment groups.
“We are delighted that rivaroxaban has now also shown benefit in a chronic setting. Rivaroxaban has previously demonstrated superior efficacy to the current standard treatment in the prevention of VTE after orthopedic surgery in all four RECORD trials. Therefore, this is the fifth study in a row in a total of more than 13,500 patients, in which rivaroxaban has shown consistent benefit in reducing the risk of VTE in patients,” said Kemal Malik, member of the Board of Management of Bayer Schering Pharma AG, Germany, responsible for Global Development.
To be eligible for enrollment in Einstein-EXT, patients must have previously completed 6 or 12 months of treatment with a vitamin K antagonist (VKA) for an acute episode of VTE or had participated in the ongoing phase-III Einstein-DVT or Einstein-PE trials, in which patients were treated with either rivaroxaban or a VKA, for the same duration of time. Patients were then randomized to receive either 20 mg of rivaroxaban dosed once-daily, or a placebo, and were evaluated for an additional six or 12 months.
Einstein is a global clinical development program composed of three clinical studies in approximately 8,000 patients.
Rivaroxaban is a novel oral anticoagulant that was invented in Bayer’s Wuppertal laboratories in Germany, and is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development.