Stroke Prevention in Atrial Fibrillation
An Expert Commentary With
Clyde W. Yancy, MD
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 an educational grant from
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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CME Information: Physicians
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Discussant
Clyde W. Yancy, MD, MSc
Magerstadt Professor of Medicine
Northwestern University
Feinberg School of Medicine
Chief of Cardiology
Northwestern Memorial Hospital
Chicago, Illinois
Disclosure Information
Clyde W. Yancy, MD, MSc,
has disclosed that he has no relevant
financial relationships or conflicts of
interest to report.
Disclosure Information
Michael Mullen, MD, Clinical Instructor of Vascular
Neurology, University of Pennsylvania; Peggy Peck; 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.
Atrial Fibrillation — Profiling Afib
• Atrial fibrillation (Afib) affects about 1% of
the population or about 2.3 million people
in the United States
• Prevalence increases with age — affecting
roughly 10% of population age 80 or older
• Afib is associated with a four- to five-fold
increase in risk of stroke
Cardiac Comorbidities Associated With Afib
•
•
•
•
•
•
•
•
Hypertension
Coronary artery disease
Valvular heart disease
Congestive heart failure
Cardiomyopathy
Pericarditis
Congenital heart disease
Cardiac surgery
Source: Clin J Am Nephrol 2010; 5: 173-181
Noncardiac Comorbidities Associated With Afib
• Pulmonary embolism
• Chronic obstructive pulmonary disease (COPD)
• Obstructive sleep apnea
• Hyperthyroidism
• Obesity
Source: Clin J Am Nephrol 2010; 5: 173-181
Atrial Fibrillation and Congestive Heart Failure
• Congestive heart failure affects 15-20 million
people worldwide
• CHF is the most important risk factor for afib
in developed nations
• Roughly 66% of CHF patients are >65
• Framingham data: CHF increased the risk of
AF 4.5-fold in men and 5.9-fold in women
Source: Europace 2004; 5: S5-S19
Warfarin for Prevention of Stroke in Patients
With Atrial Fibrillation
• Meta-analysis of 16 trials: 9,874 patients;
mean follow-up 1.7 years
• Results: Adjusted-dose warfarin associated
with a 62% reduction in the relative risk of
stroke; Absolute risk reduction 2.7% per year
for primary prevention and 8.4% per year for
secondary stroke prevention
Source: Ann Intern Med 1999; 131: 492-501
Recommended Therapeutic Range for Oral
Anticoagulant Therapy*
Indication
INR
Prevention of systemic embolism
2.0-3.0
Tissue heart valves
2.0-3.0
AMI (to prevent systemic embolism)†
2.0-3.0
Valvular heart disease
2.0-3.0
Atrial fibrillation
2.0-3.0
*Adapted from Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, Deykin D,
Brandt JT. “Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal
therapeutic range.” Chest 1998; 114(5 Suppl): 445S-469S.
†If oral anticoagulant therapy is elected to prevent recurrent myocardial infarction, an INR of
2.5-3.5 is recommended, consistent with recommendations of the Food and Drug
Administration.
AMI indicates acute myocardial infarction; INR, international normalized ratio.
Source: Baylor University Medical Center Proceedings
Home Monitoring: An Option for the
Well-Motivated Patient
• The Home INR Study (THINRS) to compare
methods among 2,922 warfarin-treated patients
at VA centers
• Weekly finger-stick INR associated with
nonsignificant decrease in bleeding, stroke, or
death compared with clinic monitoring (P=0.10)
Source: Jacobson AK, et al "A Prospective Randomized Controlled Trial of the
Impact of Home INR Testing on Clinical Outcomes: The Home INR Study
(THINRS)" AHA 2008; Abstract 5217.
Home Monitoring: An Option for the
Well-Motivated Patient (cont’d)
• Home monitoring reduced time outside of
therapeutic range by 7%
• “Overall, the findings support home testing as
an acceptable alternative to high-quality clinic
care or even preferable if patients have
difficulty getting to the clinic because of
disability or distance.”
Source: Jacobson AK, et al "A prospective randomized controlled trial of the
impact of home INR testing on clinical outcomes: The Home INR Study (THINRS)"
AHA 2008; Abstract 5217.
But Home Monitoring …
• “Over three years of follow-up in the trial,
home monitoring did not reduce the primary
endpoint of annual rate of first-time major
bleeding events, stroke, and death
significantly compared with clinic-based
monitoring (hazard ratio 0.868, 95%
confidence interval 0.733 to 1.026, P=0.10).”
Source: Jacobson AK, et al "A prospective randomized controlled trial of the
impact of home INR testing on clinical outcomes: The Home INR Study (THINRS)"
AHA 2008; Abstract 5217.
The Real Key: The Anticoagulation Clinic
• The researchers studied 104,541 patients
who were treated at 100 Veterans Health
Administration Clinics and found that a
longer interval between testing was a marker
for poor control whether the out-of-range
INR result was high or low
Source: Rose A, et al "Prompt repeat testing after out-of-range INR values a quality
indicator for anticoagulation care" Circ Cardiovasc Qual Outcomes 2011; published
online April 19, 2011.
RE-LY Study Overview
• In a large, randomized trial, two doses of the
direct thrombin inhibitor dabigatran were
compared with warfarin in patients who had
atrial fibrillation and were at risk for stroke
• At 2 years, the 110-mg dose of dabigatran
was found to be noninferior, and the 150-mg
dose superior, to warfarin with respect to the
primary outcome of stroke or systemic
embolism
Cumulative Hazard Rates for the Primary Outcome of Stroke
or Systemic Embolism, According to Treatment Group
Connolly SJ, et al. N Engl J Med 2009; 361: 1139-1151.
RE-LY Study Conclusion
• In patients with atrial fibrillation, dabigatran
given at a dose of 110 mg was associated with
rates of stroke and systemic embolism that
were similar to those associated with warfarin,
as well as lower rates of major hemorrhage
• Dabigatran administered at a dose of 150 mg,
as compared with warfarin, was associated
with lower rates of stroke and systemic
embolism but similar rates of major
hemorrhage
Turning off Warfarin
• “In patients receiving warfarin who have
asymptomatic excessive prolongations in their
INR results, 1 mg of oral vitamin K reliably
reduces the INR to the therapeutic range within
24 h. This therapy is more convenient, less
expensive, and might be safer than parenteral
vitamin K. Thus, it should be considered in all
non-bleeding patients receiving warfarin, who
present with INR results of 4.5 to 9.5.”
Source: Thromb Haemost 1998; 79(6): 1116-1118.
Summary
At the end of this activity, participants should understand:

Atrial fibrillation affects about 1% of the population and its prevalence increases with age

Afib is associated with a number of cardiac
comorbidities including hypertension, valvular
heart disease, coronary artery disease, and
congestive heart failure

Noncardiac comorbidities include sleep apnea,
obesity, and COPD
Summary

Warfarin has been the leading oral
anticoagulant treatment for afib

In a meta-analysis of more of 16 studies, use
of warfarin was associated with a significant
reduction in the risk of stroke

Warfarin use is also associated with an
increased risk of extracranial bleeding

The recommended INR therapeutic range for
afib patients treated with warfarin is 2.0-3.0
Summary

In a randomized trial, use of home
monitoring decreased the time outside
therapeutic range

Anticoagulation clinics are key to the
success of warfarin therapy, and recent
studies suggest that shorter intervals
between INR testing at clinics can improve
control
Summary

An alternative to warfarin is dabigatran
(Pradaxa), a direct thrombin inhibitor, which
is approved for prevention of stroke in
patients with afib

Dabigatran requires neither INR testing nor
special diets and is approved at doses of
150 mg and 75 mg bid

Unlike warfarin, which has an antidote
(vitamin K), dabigatran does not have an
antidote