Stroke Prevention in Atrial Fibrillation An Expert Commentary With Clyde W. Yancy, MD A Clinical Context Report

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Stroke Prevention in Atrial Fibrillation An
Expert Commentary With Clyde W. Yancy, MDA
Clinical Context Report
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Stroke Prevention in Atrial FibrillationExpert
Commentary

• Jointly Sponsored by
• ?
• and

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Stroke Prevention in Atrial FibrillationExpert
Commentary

• Supported in part by an educational grant from
  Ortho-McNeil, Division of Ortho-McNeil-Janssen
  Pharmaceuticals, Inc., administered by
  Ortho-McNeil Janssen Scientific Affairs, LLC.

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Stroke Prevention in Atrial FibrillationClinical
Context Series
The goal of this series is to provide up-to-date
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.
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Stroke Prevention in Atrial FibrillationClinical
Context SeriesTarget 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.
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Activity Learning Objective

• Upon successful completion of this educational
  program, participants should be able to?

• Review the relevance and significance of the
  activity in the broader context of clinical care?

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CME Information Physicians

• Statement of Accreditation
• This activity has been planned and implemented
  in accordance with the Essential Areas and
  Policies of the Accreditation Council for
  Continuing Medical Education through the joint
  sponsorship of the University of Pennsylvania
  School of Medicine and MedPage Today. The
  University of Pennsylvania School of Medicine is
  accredited by the ACCME to provide continuing
  medical education for physicians.

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CME Information

• Credit Designation
• The University of Pennsylvania School of
  Medicine Office of CME designates this enduring
  material for a maximum of 1.0 AMA PRA Category 1
  Credits. Physicians should claim only the
  credit commensurate with the extent of their
  participation in the activity.

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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 1 Elective credit. Credit
  may be claimed for one year from the date of each
  article.

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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 Centers
  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 0.75 nursing
  contact hours.

DISCLAIMER Accreditation refers to educational
content only and does not imply ANCC, CBRN, or
PIK endorsement of any commercial product or
service.
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CE Information Pharmacists

• Projects In Knowledge is accredited by the
  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 0.75 contact hours (0.075
  CEUs). The ACPE Universal Activity Number
  assigned to this knowledge-type activity is
  0052-9999-11-1515-H04-P.

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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

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Disclosure Information

• Clyde W. Yancy, MD, MSc,
• has disclosed that he has no relevant financial
  relationships or conflicts of interest to report.
  

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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.

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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

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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
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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
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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 gt65
• 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
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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
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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
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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 (P0.10)

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.
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Home Monitoring An Option for the
Well-Motivated Patient (contd)

• 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.
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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, P0.10).

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.
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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.
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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

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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.
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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

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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.
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Summary
At the end of this activity, participants should
understand

• Atrial fibrillation affects about 1 of the
  popu-lation 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

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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

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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

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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