- Eliquis ® (apixaban) use was associated with lower rates of stroke or systemic embolism and major bleeding than matched patients receiving rivaroxaban or dabigatran
- This oral presentation is one of nine Bristol-Myers Squibb-Pfizer Alliance abstracts being presented at the American College of Cardiology's 67th Annual Scientific Session & Expo
Bristol-Myers
Squibb Company (NYSE: BMY) and Pfizer
Inc. (NYSE: PFE) will present findings today from a real-world data
(RWD) analysis titled, Comparison of Effectiveness, Safety, and the
Net Clinical Outcome between Different Direct Oral Anticoagulants in
162,707 Non-Valvular Atrial Fibrillation Patients Treated in US Clinical
Practice. This is the largest RWD analysis reporting outcomes among
different direct oral anticoagulants (DOACs), including Eliquis
®
(apixaban), rivaroxaban and dabigatran, to date. In this analysis,
apixaban use was associated with significantly lower rates of both
stroke/systemic embolism (S/SE) (hazard ratio [HR]:0.83, 95% confidence
interval [CI]: 0.73 to 0.94, p=0.004) and major bleeding (MB) (HR:0.54,
95% CI: 0.50 to 0.58, p=<0.001) when compared to rivaroxaban; and
significantly lower rates of both S/SE (HR:0.69, 95% CI: 0.56 to 0.84,
p=<0.001) and MB (HR:0.77, 95% CI: 0.68 to 0.88, p=<0.001) when compared
to dabigatran.
This retrospective observational analysis utilizing pre-specified
endpoints included three 1:1 propensity score individually matched DOAC
cohorts: apixaban vs. rivaroxaban (n=125,238), apixaban vs. dabigatran
(n=54,192), and dabigatran vs. rivaroxaban (n=55,076). The analysis also
revealed that in the dabigatran vs. rivaroxaban cohort, dabigatran was
associated with a significantly lower rate of MB (HR:0.67, 95% CI: 0.60
to 0.74, p=<0.001) and a non-significantly higher rate of S/SE (HR:1.18,
95% CI: 0.98 to 1.43, p=0.080). It is important to note that, at this
time, there are no head-to-head clinical trials comparing DOACs.
Anticoagulants, including Eliquis, increase the risk of bleeding
and can cause serious, potentially fatal, bleeding. Please see important
safety information below for Eliquis, including BOXED WARNINGS.
“Most observational, real-world data analyses of direct oral
anticoagulants have used single data sources; in this analysis, we
pooled CMS Medicare data and four U.S. Managed Care claims databases,
including both commercial and Medicare Advantage lives, covering in
total more than 180 million beneficiaries annually1,2 – more
than half of the U.S. population,” said Steven Deitelzweig, M.D., System
Department Chair of Hospital Medicine, Ochsner Medical Center, New
Orleans, and one of the analysis’ primary investigators. “Being able to
see patient claims from different data sets with good representation
across the country may help decision making in clinical practice.”
Study Details: This was a retrospective observational cohort
analysis of non-valvular atrial fibrillation (NVAF) patients utilizing
pre-specified endpoints and analyzed using propensity-score matching
(PSM). It includes NVAF patients (n=162,707) from ARISTOPHANES (Anticoagulants
for Reduction In STroke: Observational Pooled
analysis on Health outcomes ANd Experience of
patientS), an ongoing real-world data analysis initiative that
now includes anonymized patient records from more than 300,000 patients.
The analysis presented at ACC includes patients who initiated apixaban,
rivaroxaban or dabigatran, from Jan. 1, 2013, to Sept. 30, 2015, pooled
from 5 large databases, including CMS fee-for-service Medicare data,
Truven MarketScan® Commercial Claims and Encounter and
Medicare Supplemental and Coordination of Benefits Database, the IMS
PharMetrics Plus™ Database, the Optum Clinformatics™ Data Mart, and the
Humana Research Database. After 1:1 DOAC-DOAC PSM in each database, the
resulting patient records were pooled. Patients were followed for a mean
of six months. Cox models were used to evaluate the rates of S/SE and of
MB across DOACs within one year of therapy initiation. Patients with
NVAF were included regardless of the dose of DOACs used.
Limitations of Real-World Data Analyses and of ARISTOPHANES: Real-world
data have the potential to supplement randomized controlled trial data
by providing additional information about how a medicine performs in
routine medical practice. Real-world data analyses have several
limitations. For example, the source and type of data used may limit the
generalizability of the results and of the endpoints. Observational
real-world studies can only evaluate association and not causality. Due
to these limitations, real-world data analyses cannot be used as
stand-alone evidence to validate the efficacy and/or safety of a
treatment. It is important to note that, at this time, there are no
head-to-head clinical trials comparing direct oral anticoagulants.
In this analysis, although PSM was used to control for multiple
confounders, there is still potential for residual bias. Claims for a
filled prescription do not indicate that the medication was consumed or
taken as prescribed. Also, medications filled over the counter or
provided as samples are not captured in the claims data.
BMS-Pfizer Alliance Real-Word Data (RWD) Program: ARISTOPHANES is
part of the Bristol-Myers Squibb-Pfizer Alliance global RWD analysis
program, ACROPOLIS™ (Apixaban ExperienCe Through Real-WOrld
POpuLatIon Studies), designed to generate
additional evidence from routine clinical practice settings to further
inform healthcare decision makers, including healthcare providers and
payers. The ACROPOLIS program includes retrospective, outcomes-based
analyses from over 16 databases around the world, including medical
records, medical and pharmacy health insurance claims data, and national
health data systems.
Analyses of real-world data allow for a broader understanding of patient
outcomes associated with Eliquis outside of the clinical trial
setting, as well as insight into other measures of healthcare delivery,
such as hospitalization and costs.
About Eliquis
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 for multiple indications in the U.S. based on efficacy and
safety data from multiple Phase 3 clinical trials. Eliquis is a
prescription medicine indicated to reduce the risk of stroke and
systemic embolism in patients with nonvalvular atrial fibrillation
(NVAF); 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; for the treatment of DVT and PE; and to reduce
the risk of recurrent DVT and PE, following initial therapy.
ELIQUIS 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 anticoagulants
-
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.
CONTRAINDICATIONS
-
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 antiplatelet agents,
other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs,
and NSAIDs.
-
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 these patients.
-
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.
ADVERSE REACTIONS
-
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.
DRUG INTERACTIONS
-
Combined P-gp and Strong CYP3A4 Inhibitors: Inhibitors of P-
glycoprotein (P-gp) and cytochrome P450 (CYP3A4) increase exposure to
apixaban and increase the risk of bleeding. For patients receiving
ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose of ELIQUIS
by 50% when ELIQUIS is coadministered with drugs that are combined
P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole,
or ritonavir). In patients already taking 2.5 mg twice daily, avoid
coadministration of ELIQUIS with combined P-gp and strong CYP3A4
inhibitors.
Clarithromycin
Although
clarithromycin is a combined P-gp and strong CYP3A4 inhibitor,
pharmacokinetic
data suggest that no dose adjustment is necessary with concomitant
administration with Eliquis.
-
Combined P-gp and Strong CYP3A4 Inducers: Avoid concomitant use
of ELIQUIS with combined P-gp and strong CYP3A4 inducers (e.g.,
rifampin, carbamazepine, phenytoin, St. John’s wort) because such
drugs will decrease exposure to apixaban.
-
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 fetus.
Please see full Prescribing Information, including BOXED WARNINGS and
Medication Guide, available at
www.bms.com
.
About ARISTOTLE
ARISTOTLE (Apixaban for Reduction In STroke
and Other ThromboemboLic Events in Atrial
Fibrillation) was designed to evaluate the efficacy and safety of Eliquis
versus warfarin for the prevention of stroke or systemic embolism. In
ARISTOTLE, 18,201 patients were randomized (9,120 patients to Eliquis
and 9,081 to warfarin). ARISTOTLE was an active-controlled, randomized,
double-blind, multi-national trial in patients with nonvalvular atrial
fibrillation or atrial flutter, and at least one additional risk factor
for stroke. Patients were randomized to treatment with Eliquis 5
mg orally twice daily (or 2.5 mg twice daily in selected patients,
representing 4.7 percent of all patients) or warfarin (target INR range
2.0-3.0), and followed for a median of 1.8 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 this field.
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 about
Bristol-Myers Squibb, visit us at BMS.com
or follow us on LinkedIn,
Twitter,
YouTube
and Facebook.
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, we have worked to make a difference for all who
rely on us. We routinely post information that may be important to
investors on our website at www.pfizer.com. In
addition, to learn more, please visit us on www.pfizer.com
and follow us on Twitter at @Pfizer
and @PfizerNews,
LinkedIn,
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and like us on Facebook at Facebook.com/Pfizer.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based on
current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Forward-looking statements in this press release should be evaluated
together with the many uncertainties that affect Bristol-Myers Squibb's
business, particularly those identified in the cautionary factors
discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the
year ended December 31, 2017, in our Quarterly Reports on Form 10-Q and
our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no
obligation to publicly update any forward-looking statement, whether as
a result of new information, future events or otherwise.
Pfizer Disclosure Notice
The information contained in this release is as of March 11, 2018.
Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or future
events or developments.
This release contains forward-looking information about Eliquis
(apixaban), including its potential benefits, that involves substantial
risks and uncertainties that could cause actual results to differ
materially from those expressed or implied by such statements. Risks and
uncertainties include, among other things, the uncertainties inherent in
research and development, including, without limitation, the ability to
meet anticipated clinical trial commencement and completion dates as
well as the possibility of unfavorable clinical trial results, including
unfavorable new clinical data and additional analyses of existing
clinical data; decisions by regulatory authorities regarding labeling
and other matters that could affect the availability or commercial
potential of Eliquis; and competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2017 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information and Factors That May Affect Future Results”, as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at
www.sec.gov
and
www.pfizer.com
.
1 Li, X et al. Effectiveness and safety of apixaban versus
warfarin in non-valvular atrial fibrillation patients in “real-world”
clinical practice. Thrombosis and Haemostasis. 2017; 6, 1,007-1,216. https://doi.org/10.1160/TH17-01-0068.
2 Amin, A et al. Risk of stroke/systemic embolism, major
bleeding and associated costs in non-valvular atrial fibrillation
patients who initiated apixaban, dabigatran, or rivaroxaban compared
with warfarin in the United States Medicare population. Current Medical
Research and Opinion. DOI: 10.1080/03007995.2017.1345729
Bristol-Myers Squibb Media: Rob Perry, 407-492-4616 rob.perry@bms.com or Investors: Timothy Power, 609-252-7509 timothy.power@bms.com orPfizer Inc. Media: Neha Wadhwa, 212-733-2835 neha.wadhwa@pfizer.com or Investors: Ryan Crowe, 212-733-8160 ryan.crowe@pfizer.com