Rivaroxaban demonstrated similar efficacy as standard therapy but was associated with a significantly reduced rate of major bleeding among patients with symptomatic venous thromboembolism.
Conventional treatment for VTE consists of heparin combined with vitamin K antagonists, but direct oral anticoagulants have been considered for acute and extended treatment of symptomatic VTE because they could eliminate the need for parenteral treatment or laboratory monitoring of anticoagulant effects.
Researchers conducted a pooled analysis of the EINSTEIN-PE and EINSTEIN-DVT studies to compare the efficacy and safety of rivaroxaban (Xarelto, Janssen Pharmaceuticals) with standard therapy.
The analyses included 8,282 patients. Of them, 4,151 received rivaroxaban 15 mg twice daily for 21 days, followed by 20 mg once daily. The other 4,131 received standard therapy, which included enoxaparin 1 mg/kg twice daily, plus either warfarin or acenocoumarol.
Treatment lasted 3, 6 or 12 months. Investigators monitored patients for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75.
Results showed the primary efficacy outcome occurred in 86 (2.1%) rivaroxaban-treated patients vs. 95 (2.3%) patients who underwent standard therapy (HR=0.89; 95% CI, 0.66-1.19).
In addition, researchers observed major bleeding in 40 (1%) patients in the rivaroxaban group compared with 72 (1.7%) patients in the standard therapy group (HR=0.54; 95% CI, 0.37-0.79).
“Bleeding is the most common complication of anticoagulant treatment. In this analysis, it occurred as often in patients receiving rivaroxaban as in patients receiving standard therapy,” the researchers wrote. “However, major bleeding — the most worrying complication — was statistically significantly less frequent in patients treated with rivaroxaban. This reduction was seen mainly in fatal and nonfatal critical-site bleeding, such as intracranial and retroperitoneal bleeding.”
Among important subgroups — including fragile patients, those with cancer, patients with a history of recurrent VTE and those exhibiting large clots — rivaroxaban was comparable in efficacy and safety to standard therapy, the researchers wrote.
: Bayer HealthCare and Janssen Pharmaceuticals supported the study, were involved in the design of the trial, and collected and analyzed the data. The researchers report honoraria, consulting fees and research grants from, as well as advisory board and employment relationships with, AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Johnson & Johnson, Pfizer, Sanofi-Aventis and other pharmaceutical companies.