Blood Pressure Control Key Factor in Stroke
Risk
Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE:
PFE) today announced the results of a pre-specified subanalysis of
the Phase 3 ARISTOTLE trial that assessed the effect of blood
pressure control on outcomes as well as the treatment effect of
Eliquis (apixaban) compared to warfarin according to blood pressure
control.1 The results showed that poor blood pressure control was
associated with a substantially higher risk of stroke or systemic
embolism, independent of Eliquis or warfarin treatment. However,
this subanalysis found consistent results for Eliquis versus
warfarin in reducing the risk of stroke, regardless of blood
pressure control.1 These data will be presented Saturday, March 29,
at the American College of Cardiology’s (ACC) 63rd Annual
Scientific Session in Washington, D.C.
“High blood pressure is a risk factor for stroke in patients
with atrial fibrillation. In this analysis, poorly controlled blood
pressure at any time during the trial increased the risk of stroke
by approximately 50 percent. The results for apixaban compared to
warfarin in reducing the risk of stroke were consistent regardless
of blood pressure,” said study lead author Meena Rao, MD, MPH, Duke
Clinical Research Institute at Duke University Medical Center.
“These data highlight the critical importance of blood pressure
control in addition to anticoagulation in helping to lower the risk
of stroke in patients with atrial fibrillation.”
In ARISTOTLE, a total of 15,916 (87.5 percent) patients had a
history of hypertension requiring treatment. During the trial, 50
percent of patients had poorly controlled hypertension (defined as
systolic blood pressure > 140 mm Hg and/or diastolic blood
pressure > 90 mm Hg) at some point. Poorly controlled
hypertension during the course of the trial was associated with a
significant 53 percent increase in the risk of stroke or systemic
embolism. Eliquis was consistent in reducing the risk of stroke or
systemic embolism versus warfarin in patients with and without poor
blood pressure control during the trial (p for interaction =
0.97).1
In this subanalysis, the effect of Eliquis in reducing the risk
of stroke and systemic embolism versus warfarin was consistent with
the main results of the ARISTOTLE trial. Further, the effect of
Eliquis in reducing the risk of stroke and systemic embolism versus
warfarin was also consistent with the results of the ARISTOTLE
trial in previously published subanalyses of other comorbidities,
including congestive heart failure, advanced age, renal impairment
and prior stroke.
A total of 11 Bristol-Myers Squibb/Pfizer alliance-sponsored
abstracts, including this ARISTOTLE subanalysis, were accepted for
presentation at the American College of Cardiology’s 63rd Annual
Scientific Session.
INDICATION
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.
IMPORTANT SAFETY
INFORMATION
WARNINGS: (A) DISCONTINUING ELIQUIS IN PATIENTS WITH
NONVALVULAR ATRIAL FIBRILLATION WITHOUT ADEQUATE CONTINUOUS
ANTICOAGULATION INCREASES RISK OF STROKE, (B) SPINAL/EPIDURAL
HEMATOMA
(A) Discontinuing ELIQUIS places patients at an increased
risk of thrombotic events. An increased rate of stroke was observed
following discontinuation of ELIQUIS in clinical trials in patients
with nonvalvular atrial fibrillation. If anticoagulation with
ELIQUIS must be discontinued for a reason other than pathological
bleeding, coverage with another anticoagulant should be strongly
considered.
(B) When neuraxial anesthesia (epidural/spinal anesthesia) or
spinal puncture is employed, patients anticoagulated or scheduled
to be anticoagulated with low molecular weight heparins,
heparinoids, or Factor Xa inhibitors for prevention of
thromboembolic complications are at risk of developing an epidural
or spinal hematoma which can result in long-term or permanent
paralysis.
The risk of these events may be increased by the use of
indwelling epidural catheters for administration of analgesia or by
the concomitant use of drugs affecting hemostasis such as
nonsteroidal anti-inflammatory drugs (NSAIDs), platelet aggregation
inhibitors, or other anticoagulants. The risk also appears to be
increased by traumatic or repeated epidural or spinal
puncture.
Monitor patients for signs and symptoms of neurologic
impairment. If neurologic compromise is noted, urgent treatment is
necessary. Consider the potential benefit versus risk before
neuraxial intervention in patients anticoagulated or to be
anticoagulated for thromboprophylaxis
CONTRAINDICATIONS
- Active pathological bleeding
- Severe hypersensitivity reaction to
ELIQUIS (apixaban) (e.g., anaphylactic reactions)
WARNINGS AND PRECAUTIONS
- Increased Risk of Stroke with
Discontinuation of ELIQUIS in Patients with Nonvalvular Atrial
Fibrillation: Discontinuing 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 patients
with nonvalvular atrial fibrillation. If ELIQUIS must be
discontinued for a reason other than pathological bleeding,
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 NSAIDs. Patients should be made aware of signs or
symptoms of blood loss and instructed to immediately report 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.
Hemodialysis does not appear to have a substantial impact on
apixaban exposure. Protamine sulfate and vitamin K would not be
expected to affect the anticoagulant activity of apixaban. There is
no experience with antifibrinolytic agents (tranexamic acid,
aminocaproic acid) in individuals receiving apixaban. There is
neither scientific rationale for reversal nor experience with
systemic hemostatics (desmopressin and aprotinin) in individuals
receiving apixaban. Use of procoagulant reversal agents such as
prothrombin complex concentrate, activated prothrombin complex
concentrate, or recombinant factor VIIa may be considered but has
not been evaluated in clinical studies. Activated charcoal reduces
absorption of apixaban thereby lowering apixaban plasma
concentrations.
- 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.
ADVERSE REACTIONS
The most common and most serious adverse reactions reported with
ELIQUIS (apixaban) 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
- 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
5 mg twice daily, the dose of ELIQUIS should be decreased when it
is coadministered with drugs that are strong dual inhibitors of
CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir, or
clarithromycin). In patients already taking 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.
- 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
The ARISTOTLE study 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 Atrial Fibrillation
Atrial fibrillation is the most common cardiac arrhythmia
(irregular heartbeat). It is estimated that approximately 5.8
million Americans and six million individuals in Europe have atrial
fibrillation. The lifetime risk of developing atrial fibrillation
is estimated to be approximately 25 percent for individuals 40
years of age or older. One of the most serious medical concerns for
individuals with atrial fibrillation is the increased risk of
stroke, which is five times higher in people with atrial
fibrillation than those without atrial fibrillation. In fact, 15
percent of all strokes are attributable to atrial fibrillation in
the U.S. Additionally, strokes due to atrial fibrillation are more
burdensome than strokes due to other causes. Atrial
fibrillation-related strokes are more severe than other strokes,
with an associated 30-day mortality of 24 percent and a 50 percent
likelihood of death within one year in patients who are not treated
with an antithrombotic.
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 to reduce the risk of stroke and systemic embolism in
patients with nonvalvular atrial fibrillation and for prophylaxis
of DVT, which may lead to PE, in patients who have undergone hip or
knee replacement surgery.
About the Bristol-Myers Squibb/Pfizer Collaboration
In 2007, Pfizer and Bristol-Myers Squibb entered into a
worldwide collaboration to develop and commercialize Eliquis, 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, please visit http://www.bms.com or follow us on
Twitter at http://twitter.com/bmsnews.
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.
1 Rao M, et al. Poorly Controlled Blood Pressure is
Independently Associated with a 50% Higher Risk of Stroke or
Systemic Embolism in Patients with Atrial Fibrillation. Poster
presented at: American College of Cardiology 2014 Scientific
Session; March 29, 2014; Washington, DC.
Photos/Multimedia Gallery Available:
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Bristol-Myers SquibbShelly Mittendorf
(Media)609-480-2951shelly.mittendorf@bms.comorRanya Dajani
(Investors)609-252-5330ranya.dajani@bms.comorRyan Asay
(Investors)609-252-5020ryan.asay@bms.comorPfizer Inc.Jennifer Kokell
(Media)917-741-4254jennifer.kokell@pfizer.comorRyan Crowe
(Investors)212-733-8160ryan.crowe@pfizer.com
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