Leverkusen, December 8, 2008 -
Results from a pre-specified pooled analysis of the RECORD clinical
trial program confirmed that the novel oral anticoagulant Xarelto®
(rivaroxaban), taken as one tablet, once-daily, was superior to
enoxaparin-based treatment regimens for the prevention of venous
thromboembolism (VTE) after total knee or hip replacement surgery with
low rates of major bleeding that were not statistically different from
the comparator. Pooled results from the four RECORD trials, involving
more than 12,500 patients, were presented at the 50th Annual Meeting of
the American Society of Hematology (ASH) in San Francisco (USA). RECORD
is the largest clinical trial program ever conducted of an oral
anticoagulant in the prevention of VTE after such surgeries.
in the leg and shortness of breath are symptoms that can herald venous
thromboembolism, which, in turn, can result in long-term complications
or death," said Dr. A.G.G. Turpie, Professor of Medicine, McMaster
University, Canada, and Principal Investigator for the RECORD program.
"As a physician, one of my goals is to reduce patients' risk of
complications, and these data show that Xarelto has the ability to
reduce the composite of symptomatic VTE and all cause mortality by half
when compared to enoxaparin."
RECORD studies evaluated Xarelto (10 mg given as one tablet,
once-daily) in the prevention of VTE following elective total knee
replacement surgery (TKR) or total hip replacement surgery (THR)
against enoxaparin at various doses and treatment durations. The pooled
analysis had a primary composite efficacy endpoint of symptomatic VTE
[symptomatic deep vein thrombosis (DVT) and symptomatic non-fatal
pulmonary embolism (PE)] and all-cause mortality, which was analyzed at
three different time points:
all three time points, patients treated with rivaroxaban demonstrated a
statistically significant reduction of more than 50% in the composite
primary efficacy endpoint compared to patients treated with enoxaparin.
Specifically, there was a 51% relative risk reduction (RRR) in those
treated with rivaroxaban vs. those treated with enoxaparin (0.8% vs.
1.6%, respectively, p<0.001) in the total study duration pool; a 58%
RRR in the total treatment duration pool (0.6% vs. 1.3%, respectively,
p<0.001) and a 52% RRR for those treated with rivaroxaban vs. those
treated with enoxaparin (0.5% vs. 1.0%, respectively, p<0.001) in
the head-to-head treatment pool.
findings confirm the results of the four individual RECORD studies,
which demonstrated the superior efficacy of Xarelto for preventing
total VTE [composite of DVT, non-fatal PE, all-cause mortality], both
in head-to-head comparisons with enoxaparin (RECORD1, 3 and 4) as well
as when comparing extended-duration (5 weeks) Xarelto with
short-duration (2 weeks) enoxaparin in RECORD2. In all four trials,
Xarelto and enoxaparin had similar safety profiles.
four pre-specified treatment-emergent bleeding safety endpoints in the
pooled analysis were assessed at two time points: the total treatment
duration pool and in the head-to-head treatment pool of 12±2 days post
demonstrated low bleeding rates, which were not statistically
significantly different in comparison to enoxaparin for three of the
four pre-specified safety endpoints (major bleeding, major bleeding
including surgical site bleeding and any bleeding) at both time points:
for the composite endpoint of major and clinically relevant non-major
bleeding were also low but statistically significantly different for
the total treatment duration time period [12±2
days following TKR and 35±4 days following THR, including extended (5
weeks) Xarelto treatment in RECORD2 compared to short-term (2 weeks)
enoxaparin, followed by placebo for 3 weeks] with 3.2% for Xarelto vs.
2.5% for enoxaparin (p=0.039). However, the rates were not
statistically significantly different in the head-to-head treatment
pool of 12±2 days, which included the majority of reported bleeding
cases in these criteria, 2.8% for Xarelto vs. 2.5% for enoxaparin
combination of the efficacy and the safety profile of Xarelto may help
change clinical practice to more accurately reflect established
anticoagulation guidelines which are in place to protect patient
lives," said Dr. Turpie. "All the results reported from the RECORD
program strengthen my belief that direct Factor Xa inhibition with
Xarelto has the potential to revolutionize the way we prevent the
formation of dangerous blood clots."
Multiple Presentations Highlight Efficacy
a separate plenary session and ASH media briefing, Dr. Turpie presented
results from the RECORD4 trial, which demonstrated that Xarelto is the
only oral anticoagulant to show clinical benefit in the head-to-head
comparison against the U.S.-approved regimen of enoxaparin. Xarelto (10
mg once-daily) provided a statistically significant 31% RRR in total
VTE events compared to enoxaparin (30 mg twice-daily) [6.9% vs. 10.1%,
respectively (p =0.012)]. Rates of major bleeding, the main safety
endpoint, were low in both treatment groups.
approved for use in the European Union for the prevention of VTE in
adult patients who have undergone elective total hip or knee
replacement surgery. Additional filings
are under review with regulatory agencies in more than 10 other
countries worldwide, including the United States.
The extensive clinical trial program supporting Xarelto makes
it the most studied oral, direct Factor Xa inhibitor in the world
today. More than 60,000 patients are expected to be enrolled into the Xarelto clinical
development program, which will evaluate the product in the prevention
and treatment of a broad range of acute and chronic blood-clotting
disorders including VTE treatment, stroke prevention in patients with
atrial fibrillation and VTE prevention in hospitalized, medically ill
invented in Bayer's Wuppertal laboratories in Germany, and is being
jointly developed by Bayer HealthCare and Johnson & Johnson
Pharmaceutical Research & Development, L.L.C.
Bayer Group is a global enterprise with core competencies in the fields
of health care, nutrition and high-tech materials. Bayer HealthCare, a
subsidiary of Bayer AG, is one of the world's leading, innovative
companies in the healthcare and medical products industry and is based
in Leverkusen, Germany. The company combines the global activities of
the Animal Health, Consumer Care, Diabetes Care and Pharmaceuticals
divisions. The pharmaceuticals business operates under the name Bayer
Schering Pharma. Bayer HealthCare's aim is to discover and manufacture
products that will improve human and animal health worldwide. Find more
information at www.bayerhealthcare.com.
Schering Pharma is a worldwide leading specialty pharmaceutical
company. Its research and business activities are focused on the
following areas: Diagnostic Imaging, General Medicine, Specialty
Medicine and Women's Healthcare. With innovative products, Bayer
Schering Pharma aims for leading positions in specialized markets
worldwide. Using new ideas, Bayer Schering Pharma aims to make a
contribution to medical progress and strives to improve the quality of
life. Find more information at www.bayerscheringpharma.de.
Copies of the abstracts may be viewed online at www.hematology.org/meetings/abstracts.cfm
To learn more about thrombosis please visit www.thrombosisadviser.com and to learn more about Xarelto please visit www.xarelto.com
Alexander Siedler, Tel.: +49 30-468-12727
Last Updated on Thursday, 05 February 2009 06:39
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