Secondary Analysis of AMPLIFY-EXT Examining Predictors of Hospitalization
Presented at ESC Congress: Eliquis (apixaban) Significantly Reduced the Risk
of All-Cause Hospitalization Versus Placebo in Patients with Venous
PRINCETON, N.J. & NEW YORK -- August 30, 2014
Bristol-Myers Squibb Company (NYSE:BMY) and Pfizer Inc. (NYSE:PFE) today
announced results of a pre-specified secondary analysis of the Eliquis Phase 3
AMPLIFY-EXT trial (Apixaban after the initial Management of PuLmonary embolIsm
and deep vein thrombosis with First-line therapY-EXTended Treatment). The
analysis evaluated clinical and demographic predictors of all-cause
hospitalization in patients with VTE, which includes deep vein thrombosis
(DVT) and pulmonary embolism (PE). Results from this analysis demonstrated
that during the 12-month extended treatment of VTE, Eliquis significantly
reduced the risk of hospitalization versus placebo. This effect was
independent of other variables including renal function, the only other
significant predictor of hospitalization in the AMPLIFY-EXT population. These
data were presented during an oral session today in Barcelona, Spain, at the
ESC Congress 2014.
“The results of this AMPLIFY-EXT secondary analysis showed that Eliquis
significantly reduced the risk of hospitalization, irrespective of other
variables,” said Dr. Alexander T. Cohen, study investigator and consultant
physician, Department of Hematology, Guy’s and St. Thomas’ Hospitals, King’s
College, London. “The findings from this secondary analysis provide additional
support for extended anticoagulation with Eliquis in VTE patients.”
AMPLIFY-EXT was a randomized, double-blind, placebo-controlled extended
treatment superiority study with 12 months of treatment plus one month
follow-up in patients with VTE who completed six to 12 months of
anticoagulation therapy. The secondary analysis presented today showed that,
compared with placebo, Eliquis 2.5 mg (p=0.032) and 5 mg (p=0.004) were both
associated with significant reduction in all-cause hospitalization. Of the
2,486 patients included in the AMPLIFY-EXT trial, 138 patients were
hospitalized at least once, including 62 (7.48%) in the placebo group (n=829),
42 (5.00%) in the Eliquis 2.5 mg group (n=840), and 34 (4.18%) in the Eliquis
5 mg group (n=813). ^ Of the first hospitalizations in the placebo group, a
total of 32 (51.6%) were attributed to VTE recurrence versus six (17.7%) in
the Eliquis 5 mg group and 11 (26.2%) in the Eliquis 2.5 mg group.
The following factors were clinically significant and independent predictors
of all-cause hospitalization during the trial:
*Eliquis 2.5 mg versus placebo (HR=0.65, 95% CI=0.43-0.96)
*Eliquis 5 mg versus placebo (HR=0.54, 95% CI=0.36-0.83)
*Severe or moderate renal impairment versus normal renal function (HR=2.26,
Sex, age, baseline body weight and type of VTE did not significantly predict
A total of 14 Bristol-Myers Squibb/Pfizer alliance-sponsored abstracts,
including the AMPLIFY-EXT pre-specified secondary analysis described above,
were accepted for presentation at the ESC Congress 2014.
Eliquis (apixaban) is an oral selective Factor Xa inhibitor. By inhibiting
Factor Xa, a key blood clotting protein, Eliquis decreases thrombin generation
and blood clot formation. Eliquis is approved to reduce the risk of stroke and
systemic embolism in patients with nonvalvular atrial fibrillation in the
United States, European Union, Japan and a number of other countries around
the world. Eliquis is approved for prevention of VTE in adult patients who
have undergone elective hip or knee replacement surgery in the United States,
European Union and a number of other countries around the world. Eliquis is
not approved for this indication in Japan. Eliquis is approved for the
treatment of DVT and PE, and prevention of recurrent DVT and PE following
initial therapy in the United States and European Union.
ELIQUIS Important Safety Information
ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in
patients with nonvalvular atrial fibrillation.
ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which
may lead to pulmonary embolism (PE), in patients who have undergone hip or
knee replacement surgery.
ELIQUIS is indicated for the treatment of DVT and PE, and to reduce the risk
of recurrent DVT and PE following initial therapy.
Important Safety Information
WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF
THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA
(A) Premature discontinuation of any oral anticoagulant, including ELIQUIS,
increases the risk of thrombotic events. If anticoagulation with ELIQUIS is
discontinued for a reason other than pathological bleeding or completion of a
course of therapy, consider coverage with another anticoagulant.
(B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS
who are receiving neuraxial anesthesia or undergoing spinal puncture. These
hematomas may result in long-term or permanent paralysis. Consider these risks
when scheduling patients for spinal procedures. Factors that can increase the
risk of developing epidural or spinal hematomas in these patients include:
*use of indwelling epidural catheters
*concomitant use of other drugs that affect hemostasis, such as
nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other
*a history of traumatic or repeated epidural or spinal punctures
*a history of spinal deformity or spinal surgery
*optimal timing between the administration of ELIQUIS and neuraxial
procedures is not known
Monitor patients frequently for signs and symptoms of neurological impairment.
If neurological compromise is noted, urgent treatment is necessary.
Consider the benefits and risks before neuraxial intervention in patients
anticoagulated or to be anticoagulated.
*Active pathological bleeding
*Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions)
WARNINGS AND PRECAUTIONS
*Increased Risk of Thrombotic Events after Premature Discontinuation:
Premature discontinuation of any oral anticoagulant, including ELIQUIS, in
the absence of adequate alternative anticoagulation increases the risk of
thrombotic events. An increased rate of stroke was observed during the
transition from ELIQUIS to warfarin in clinical trials in atrial
fibrillation patients. If ELIQUIS is discontinued for a reason other than
pathological bleeding or completion of a course of therapy, consider
coverage with another anticoagulant.
*Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause
serious, potentially fatal bleeding.
*Concomitant use of drugs affecting hemostasis increases the risk of
bleeding including aspirin and other anti-platelet agents, other
anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and
*Advise patients of signs and symptoms of blood loss and to report
them immediately or go to an emergency room. Discontinue ELIQUIS in
patients with active pathological hemorrhage.
*There is no established way to reverse the anticoagulant effect of
apixaban, which can be expected to persist for at least 24 hours
after the last dose (i.e., about two half-lives). A specific antidote
for ELIQUIS is not available.
*Spinal/Epidural Anesthesia or Puncture: Patients treated with Eliquis
undergoing spinal/epidural anesthesia or puncture may develop an epidural
or spinal hematoma which can result in long-term or permanent paralysis.
The risk of these events may be increased by the postoperative use of
indwelling epidural catheters or the concomitant use of medicinal products
affecting hemostasis. Indwelling epidural or intrathecal catheters should not
be removed earlier than 24 hours after the last administration of ELIQUIS. The
next dose of ELIQUIS should not be administered earlier than 5 hours after the
removal of the catheter. The risk may also be increased by traumatic or
repeated epidural or spinal puncture. If traumatic puncture occurs, delay the
administration of ELIQUIS for 48 hours.
Monitor patients frequently and if neurological compromise is noted, urgent
diagnosis and treatment is necessary. Physicians should consider the potential
benefit versus the risk of neuraxial intervention in Eliquis patients.
*Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been
studied in patients with prosthetic heart valves and is not recommended in
*Acute PE in Hemodynamically Unstable Patients or Patients who Require
Thrombolysis or Pulmonary Embolectomy: Initiation of ELIQUIS is not
recommended as an alternative to unfractionated heparin for the initial
treatment of patients with PE who present with hemodynamic instability or
who may receive thrombolysis or pulmonary embolectomy.
*The most common and most serious adverse reactions reported with ELIQUIS
were related to bleeding.
TEMPORARY INTERRUPTION FOR SURGERY AND OTHER INTERVENTIONS
*ELIQUIS should be discontinued at least 48 hours prior to elective surgery
or invasive procedures with a moderate or high risk of unacceptable or
clinically significant bleeding. ELIQUIS should be discontinued at least
24 hours prior to elective surgery or invasive procedures with a low risk
of bleeding or where the bleeding would be noncritical in location and
easily controlled. Bridging anticoagulation during the 24 to 48 hours
after stopping ELIQUIS and prior to the intervention is not generally
required. ELIQUIS should be restarted after the surgical or other
procedures as soon as adequate hemostasis has been established.
*Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of CYP3A4 and P-gp
increase exposure to apixaban and increase the risk of bleeding. For
patients receiving ELIQUIS doses greater than 2.5 mg twice daily, the dose
of ELIQUIS should be decreased by 50% when it is coadministered with drugs
that are strong dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole,
itraconazole, ritonavir, or clarithromycin). For patients receiving
ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with
strong dual inhibitors of CYP3A4 and P-gp.
*Strong Dual Inducers of CYP3A4 and P-gp: Avoid concomitant use of ELIQUIS
with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin,
carbamazepine, phenytoin, St. John’s wort) because such drugs will
decrease exposure to apixaban and increase the risk of stroke and other
*Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet
agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases
the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of
apixaban in high-risk post-acute coronary syndrome patients treated with
aspirin or the combination of aspirin and clopidogrel, was terminated
early due to a higher rate of bleeding with apixaban compared to placebo.
PREGNANCY CATEGORY B
*There are no adequate and well-controlled studies of ELIQUIS in pregnant
women. Treatment is likely to increase the risk of hemorrhage during
pregnancy and delivery. ELIQUIS should be used during pregnancy only if
the potential benefit outweighs the potential risk to the mother and
Please see full Prescribing Information, including BOXED WARNINGS and
Medication Guide, available at www.bms.com.
About DVT and PE
VTE encompasses two serious conditions: DVT, a blood clot in a deep vein,
usually in the lower leg, thigh, or pelvis, which partially or totally blocks
the flow of blood; and PE, a blood clot that blocks one or more vessels in the
lungs. Approximately one million patients in the EU are diagnosed every year
with VTE. In the U.S., the number of adults with VTE is projected to more than
double from 950,000 in 2006 to 1.82 million in 2050. Once a VTE has occurred,
approximately 33% of patients may experience a recurrence within 10 years.
About the Bristol-Myers Squibb/Pfizer Collaboration
In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide
collaboration to develop and commercialize apixaban, an oral anticoagulant
discovered by Bristol-Myers Squibb. This global alliance combines
Bristol-Myers Squibb's long-standing strengths in cardiovascular drug
development and commercialization with Pfizer’s global scale and expertise in
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to
discover, develop and deliver innovative medicines that help patients prevail
over serious diseases. For more information, please
visithttp://www.bms.comor follow us on Twitter
About Pfizer Inc.: Working together for a healthier world™
At Pfizer, we apply science and our global resources to bring therapies to
people that extend and significantly improve their lives. We strive to set the
standard for quality, safety and value in the discovery, development and
manufacture of health care products. Our global portfolio includes medicines
and vaccines as well as many of the world's best-known consumer health care
products. Every day, Pfizer colleagues work across developed and emerging
markets to advance wellness, prevention, treatments and cures that challenge
the most feared diseases of our time. Consistent with our responsibility as
one of the world's premier innovative biopharmaceutical companies, we
collaborate with health care providers, governments and local communities to
support and expand access to reliable, affordable health care around the
world. For more than 150 years, Pfizer has worked to make a difference for all
who rely on us. To learn more, please visit us at www.pfizer.com.
Danielle Halstrom, 609-252-3403
Ranya Dajani, 609-252-5330
Ryan Asay, 609-252-5020
Jennifer Kokell, 212-733-2596
Andrew Widger, +44 1737 330 909
Ryan Crowe, 212-733-8160
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