Stroke Prevention in Atrial Fibrillation
An Expert Commentary With
Freek W.A. Verheugt, MD, FACC, FESC
A Clinical Context Report
Stroke Prevention in Atrial Fibrillation
Expert Commentary
Jointly Sponsored by:
and
Stroke Prevention in Atrial Fibrillation
Expert Commentary
Supported in part by educational grants from
Bristol-Myers Squibb, Pfizer and
Ortho-McNeil, Division of Ortho-McNeilJanssen Pharmaceuticals, Inc., administered
by Ortho-McNeil Janssen Scientific Affairs,
LLC.
Stroke Prevention in Atrial Fibrillation
Clinical Context Series
The goal of this series is to provide up-todate information and multiple perspectives
on the pathogenesis, symptoms, risk
factors, and complications of stroke
prevention in atrial fibrillation, as well as
current and emerging treatments, and best
practices in the management of stroke
prevention in atrial fibrillation.
Stroke Prevention in Atrial Fibrillation
Clinical Context Series
Target Audience
Electrophysiologists, cardiologists,
primary care physicians, nurses, nurse
practitioners, physician assistants,
pharmacists, and other healthcare
professionals involved in the management
of stroke prevention in atrial fibrillation.
Activity Learning Objective
CME Information: Physicians

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for Continuing Medical Education through the
joint sponsorship of the University of
Pennsylvania School of Medicine and MedPage
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of Medicine is accredited by the ACCME to
provide continuing medical education for
physicians.
CME Information

Credit Designation
The University of Pennsylvania School of
Medicine Office of CME designates this
enduring material for a maximum of 0.5 AMA
PRA Category 1 Credits.™ Physicians should
claim only the credit commensurate with the
extent of their participation in the activity.
CME Information: Physicians

Credit for Family Physicians
MedPage Today "News-Based CME" has
been reviewed and is acceptable for up to
2098 Elective credits by the American
Academy of Family Physicians. AAFP
accreditation begins January 1, 2011. Term of
approval is for one year from this date. Each
article is approved for 0.5 Elective credit.
Credit may be claimed for one year from the
date of each article.
CE Information: Nurses

Statement of Accreditation
– Projects In Knowledge, Inc. (PIK) is accredited
as a provider of continuing nursing education
by the American Nurses Credentialing
Center’s Commission on Accreditation.
– Projects In Knowledge is also an approved
provider by the California Board of Registered
Nursing, Provider Number CEP-15227.
– This activity is approved for 0.5 nursing
contact hours.
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Accreditation Council for Pharmacy Education
(ACPE) as a provider of continuing pharmacy
education. This program has been planned and
implemented in accordance with the ACPE
Criteria for Quality and Interpretive Guidelines.
This activity is worth up to 0.5 contact hours
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Number assigned to this knowledge-type activity
is 0052-9999-11-2433-H04-P.
Discussant
Freek W.A. Verheugt, MD, FACC, FESC
Professor of Cardiology
Chairman, Department of Cardiology
Onze Lieve Vrouwe Gasthuis
Amsterdam, The Netherlands
Disclosure Information
Freek W.A. Verheugt, MD, FACC, FESC
has disclosed the following relevant financial
relationship:
Served on the Speakers Bureau for Bayer
HealthCare Pharmaceuticals
Disclosure Information
Michael Mullen, MD, Clinical Instructor of Vascular
Neurology, University of Pennsylvania; Chris Kaiser; and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner,
have disclosed that they have no relevant financial
relationships or conflicts of interest with commercial interests
related directly or indirectly to this educational activity.
The staff of The University of Pennsylvania School of
Medicine Office of CME, MedPage Today, and Projects In
Knowledge have no relevant financial relationships or
conflicts of interest with commercial interests related directly
or indirectly to this educational activity.
Primary Event Rate Per Year: Warfarin vs.
Aspirin
• Patients <75 years – 1.3% vs. 1.9%
• Patients >75 years – 3.6% vs. 4.8%
Data from the SPAF-II (Stroke Prevention in Atrial Fibrillation II) study.
Source: Lancet 1994; 343(8899): 687-691.
Annual Event Risk Per Year
• Warfarin: 3.93%
• Aspirin Plus Clopidogrel: 5.60%
• The relative risk for a vascular event was
1.44 for those on clopidogrel plus aspirin
compared with those on warfarin
Data from the ACTIVE W (Atrial fibrillation Clopidogrel Trial with Irbesartan for
prevention of Vascular Events) trial.
Source: Lancet 2006; 367(9526): 1903-1912.
Three Major Trials of New Afib Drugs
• RE-LY trial
• Twice-daily dabigatran (Pradaxa), an oral direct
thrombin inhibitor
• Found superior to warfarin
• ROCKET-AF
• Once-daily rivaroxaban (Xarelto), an oral direct factor
Xa inhibitor
• Found noninferior to warfarin
• ARISTOTLE
• Twice-daily apixaban (Elquis), an oral direct factor Xa
inhibitor
• Found superior to warfarin
Approval of New Afib Drugs
• Dabigatran
• Approved in Europe, the U.S., and Canada for
thromboembolic prevention in patients with atrial
fibrillation and those undergoing knee or hip
replacement surgery
• Rivaroxaban
• Approved in Europe, the U.S. and Canada for
prevention of deep vein thrombosis in patients
undergoing knee or hip replacement surgery
• Apixaban
• Approved in Europe for thromboembolic prevention
in patients undergoing knee or hip replacement
surgery
Cost of Warfarin Versus Dabigatran
• Warfarin per year: $109 retail ($0.30/day),
$1,700 INR monitoring
• Dabigatran per year: $2,737 retail ($7.50/day)1
• Turakhia, et al. found dabigatran cost-effective
in those over 65 years at risk for stroke with an
estimated cost of $45,372 per QALY. That
analysis was based on the cost of high-dose
dabigatran being $13 per dose2
Sources:
1. BOLT International Market Research.
2. Ann Intern Med 2011; 154(1): 1-11.
Warfarin Patients in Optimal Therapeutic Range
• RE-LY: 66%1
• ROCKET-AF: 54%2
• ARISTOTLE: 62%3
Sources:
1. N Engl J Med 2009; 361: 1139-1151.
2. N Engl J Med 2011; 365: 883-891.
3. N Engl J Med 2011; 365: 981-992.
Shortcomings of Warfarin
• Interacts with some foods
• Interacts with many commonly-used
medications
• Has to be monitored via blood draws to
maintain effective therapeutic range
• Onset of clotting mechanism takes about a day
• Risk of hemorrhage
Summary
At the end of this activity, participants should understand:

Warfarin maintenance has challenges

A newer class of oral anticoagulants, including
dabigatran, rivaroxaban, and apixaban, will
challenge the dominance of warfarin

These novel agents have proven either noninferior
or superior to warfarin in large clinical trials

It’s currently unknown how quickly these new
drugs will be adopted