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Xarelto vs aspirin

Xarelto superior to aspirin for long-term prevention of VTE

EINSTEIN CHOICE met its primary endpoint, finding both Xarelto doses (10mg and 20mg) to be superior to aspirin in preventing recurrent VTE

Phase 3 results from EINSTEIN CHOICE clinical trial has revealed patients with venous thromboembolism (VTE) taking Xarelto(rivaroxaban), who received either 10mg or 20mg once daily over an extended time period, had significantly fewer recurrent blood clots and similar rates of major bleeding compared to those taking aspirin 100mg once daily. Specifically, Xarelto10mg reduced the risk of recurrent VTE by 74 percent and Xarelto20mg by 66 percent.

These findings were presented during a Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials session at the American College of Cardiology's 66th Annual Scientific Session (ACC.17) and published simultaneously in The New England Journal of Medicine. EINSTEIN CHOICE is part of the industry-leading EXPLORER clinical research programme for Xarelto, a collaborative effort between Janssen Pharmaceuticals and its development partner, Bayer.

People with VTE are at risk of having another occurrence, guidelines currently recommend anticoagulant therapy with a non-vitamin K antagonist oral anticoagulant (NOAC), like XARELTO®, for three months or longer.

Once anticoagulant therapy is stopped, up to 10 percent of people will experience a recurrence during the first year and up to 20 percent within three years. In people who decide to stop anticoagulant therapy, guidelines currently suggest using aspirin for long-term prevention of recurrent VTE rather than no aspirin at all. The EINSTEIN CHOICE study was designed to compare the efficacy and safety of Xarelto to aspirin for continued VTE management.

"How best to extend anticoagulant use beyond the initial treatment window has been a constant source of debate, with physicians carefully balancing patients' risk of another VTE with the risk of anticoagulant-related bleeding," said study investigator, Dr Philip S Wells, Professor, Chair and Chief, Department of Medicine, University of Ottawa, and Senior Scientist, The Ottawa Hospital, Ontario, Canada. "With EINSTEIN CHOICE, for the first time we have clinical evidence confirming rivaroxaban is superior to aspirin in reducing recurrent VTE, with no significant impact on safety. These important results have the potential to trigger a paradigm shift in how physicians manage their patients and protect them from VTE recurrence over the long term."

EINSTEIN CHOICE met its primary endpoint, finding both Xarelto doses (10mg and 20mg) to be superior to aspirin in preventing recurrent VTE. Researchers observed the following:

The rate of recurrent VTE was 1.2 percent in the Xarelto10 mg group (HR=0.26; 95% CI, 0.14 to 0.47; p<0.001) and 1.5 percent in the Xarelto 20mg group (HR=0.34; 95% CI, 0.20 to 0.59; p<0.001) compared to 4.4 percent in the aspirin group. Fatal VTE occurred in 0 percent, 0.2 percent and 0.2 percent, respectively.

Rates of major bleeding were comparable and low across all treatment groups at 0.4 percent for Xarelto 10mg (HR=1.64; 95% CI, 0.39 to 6.84; p=0.50), 0.5 percent for Xarelto20mg (HR=2.01; 95% CI, 0.50 to 8.04; p=0.32) and 0.3 percent for aspirin. Rates of clinically relevant non-major bleeding also were similar between the groups at 2.0 percent, 2.7 percent and 1.8 percent, respectively.

Other efficacy outcomes were evaluated in the study. Researchers found 1.9 percent of the Xarelto 10mg group (HR=0.33; 95% CI, 0.20 to 0.54; p<0.001) and 2.0 percent of the Xarelto 20mg group (HR=0.35; 95% CI, 0.22 to 0.57; p<0.001) experienced either a recurrent VTE (primary efficacy endpoint), heart attack, ischaemic stroke, systemic embolism or venous thrombosis in another location compared to 5.6 percent of the aspirin group. Recurrent VTE or all-cause mortality occurred in 1.3 percent of the Xarelto 10mg group (HR=0.27; 95% CI, 0.15 to 0.47; p<0.001) and 2.1 percent of the Xarelto 20mg group (HR=0.42; 95% CI, 0.26 to 0.68; p<0.001) compared to 4.9 percent of the aspirin group. When looking at pre-specified subgroups, researchers found results for the primary efficacy endpoint (recurrent VTE) and composite outcome of major and clinically relevant non-major bleeding to be consistent with the overall findings.

"In addition to confirming findings from previous studies examining the long-term use of Xareltoin VTE, EINSTEIN CHOICE provides valuable clinical insights on the superiority of Xareltoto aspirin as well as the potential extended use of a lower dose of Xareltofor continued venous protection," said Dr Paul Burton, Vice President, Medical Affairs, Janssen. "We look forward to discussing these important data with the FDA."

EINSTEIN CHOICE was led by principal investigator, Dr Jeffrey Weitz, Professor of Medicine, Michael G. DeGroote School of Medicine, McMaster University, and Director of McMaster's Thrombosis & Atherosclerosis Research Institute. This Phase 3, global, randomised, double-blind, superiority study compared the efficacy and safety of two doses of Xarelto(a prophylactic dose of 10mg once daily and a treatment dose of 20mg once daily) with aspirin 100mg once daily for the continued management of VTE in people with confirmed DVT or PE who were initially treated with anticoagulant therapy for six to 12 months.

 Approximately 3,365 patients from 31 countries were included in the study analysis. Importantly, people who required extended anticoagulation at therapeutic doses were not included, as the objective of the study was to investigate those patients for whom the treating physician was uncertain about the need for continuing anticoagulant therapy.

Patients were randomised in a 1:1:1 ratio, with one group receiving Xarelto 10mg, another group receiving Xarelto 20mg, and a third receiving aspirin 100mg, all given once daily for up to 12 months. Sixty percent of patients completed the full 12 months of treatment. The primary efficacy endpoint was fatal or non-fatal recurrent VTE (a composite of recurrent VTE, VTE-related death and unexplained death for which PE could not be excluded).

"With slightly more than one million Americans discharged from the hospital each year with either a primary or secondary diagnosis of ACS, it is important for the scientific community to continue investigating different treatment approaches for vascular protection aimed at preventing secondary cardiovascular events in these patients," said Dr Burton. "Results from this preliminary study find Xarelto and aspirin to have similar safety post-ACS, and we intend to use this research to inform future plans for examining Xarelto in this population."