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Defining Moments in Non-Valvular Atrial Fibrillation: Pathophysiology and consequences of Ischemic stroke

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Defining Moments in Non-Valvular Atrial Fibrillation: Pathophysiology and consequences of Ischemic stroke

  1. 1. Defining Moments in Non-Valvular Atrial Fibrillation Pathophysiology and Consequences of Ischemic Stroke
  2. 2. Disclaimer MEDICAL LITERATURE AND GUIDELINES MAY HAVE CHANGED SINCE THE POSTING OF THIS CONTENT. THE COMPANY THAT CREATED THIS PRESENTATION DOES NOT MAKE ANY REPRESENTATION OR WARRANTY RELATED TO THE MEDICAL ACCURACY OF THIS CONTENT. NOTHING IN THIS PRESENTATION IS INTENDED TO REPLACE CLINICAL JUDGMENT OR DICTATE INDIVIDUAL PATIENT CARE. THE COMPANY THAT CREATED THIS PRESENTATION IS NOT INTENDING TO OFFER ANY MEDICAL OPINION AND IS NOT ENGAGING IN MEDICAL PRACTICE THROUGH THE DISTRIBUTION OF THIS PRESENTATION.
  3. 3. Approximately 8 Ischemic Strokes Due to Atrial Fibrillation Occur Every Hour in the United States ~ 795,000 strokes annually1 ~ 87% ~ 691,650 ischemic strokes1 ~ 20% ~ 138,330 cardioembolic2 ~ 50% ~ 69,165 cardioembolic ischemic strokes due to AFib annually2,3 1. Go AS et al. Circulation. 2013;127:e6-e245. 2. Sacco RL et al. Stroke. 2006;37:577-617. 3. Freeman WD et al. Neurotherapeutics. 2011;8:488-502. 4. Steger C et al. Eur Heart J. 2004;25:1734-1740.. 5. Gattellari M et al. Cerebrovasc Dis. 2011;32:370-382. Approximately 8 ischemic strokes/hr due to AFib in the US More likely to be bedridden, disabling, and fatal than non-AFib-related ischemic strokes4,5
  4. 4. Overview and Pathophysiology
  5. 5. Atrial Fibrillation Is the Most Common Cause of Cardioembolic Ischemic Stroke Cardiac Diseases Leading to Cardioembolic Events 15% Atrial fibrillation Ventricular thrombus 15% 50% Valvular heart disease 20% Structural heart defects or tumors 1. Freeman WD, Aguilar MI. Neurol Clin. 2008;26:1129-1160.
  6. 6. Ischemic Stroke Risk Factors Are Common in Patients With Atrial Fibrillation 6 70 5 60 N=1084 50 44.2 40 30 20 10 0 5.49 67.3 23.5 28.5 17.3 9.1 40.8 HR for event Percentage of patients Prevalence of risk factors for ischemic 80 Hazard ratio for ischemic stroke without anticoagulation2 stroke1* N=90,490 4 2.96 3 2 1 0.98 0 HR=hazard ratio; TIA=transient ischemic attack; TE=thromboembolic event. *Patients with NVAF not on anticoagulation. 1. Lip GYH, et al. Chest. 2010;137:263-272. 2. Friberg L et al. Eur Heart J. 2012;33:1500-1510. 1.19 1.19 1.07 1.21
  7. 7. Atrial Fibrillation Predisposes to the Formation of Clots in the Left Atrium and Appendage Blood stasis To carotid artery Abnormal blood constituents Left atrium thrombus Anatomical and structural defects Watson T et al. Lancet. 2009;373:155-166.
  8. 8. Smaller Vessels Make the Brain Vulnerable to Cardioembolic Ischemia MCA1 ACA ACA/PCA2 Cardioembolic clot3 LAD artery (proximal)4 Femoral artery5 ACA=anterior cerebral artery; LAD=left anterior descending; MCA=middle cerebral artery; PCA=posterior cerebral artery. 1. Zurada A et al. Clin Anat. 2011;24:34-46. 2. Ashwini CA et al. Neuroanatomy. 2008;7:54-65. 3. Marder VJ et al. Stroke. 2006;37:2086-2093. 4. Dodge JT et al. Circulation. 1992;86:232-246. 5. Sandgren T et al. J Vasc Surg. 1999;29:503-510 MCA PCA
  9. 9. Ischemia From Cardioembolic Thrombi Cause Neurologic Damage to Vast Areas of Brain Territory ACA territory MCA territory PCA territory ACA=anterior cerebral artery; MCA=middle cerebral artery; PCA=posterior cerebral artery. 1. Maas MB, Safdieh JE. Neurology. 2009;13:1-16.
  10. 10. Acute and Long-term Effects of Ischemic Strokes Due to Atrial Fibrillation • Severity of acute presentation • Hospital course complications • Short- and long-term disability • Short- and long-term mortality
  11. 11. Clinical Outcome Measures for Ischemic Stroke Modified Rankin Scale1 Barthel Index2 • Measures degree of disability or dependence in daily activities • Score of 0-6 • Measure of the ability to perform self-care and activities of daily living • Rates 10 performance items on a point scale – 0: No symptoms – 1: No significant disability despite symptoms – 2: Slight disability – 3: Moderate disability – 4: Moderately severe disability – 5: Severe disability – 6: Dead – Feeding, bathing, dressing, bowel s, stairs, bladder, toilet use, transfers (bed to chair and back), grooming, and mobility • Score 0-100 – A higher score is associated with a greater likelihood of living at home with a degree of independence 1. Strokecenter.org. http://www.strokecenter.org/wp-content/uploads/2011/08/modified_rankin.pdf. Accessed March 1, 2013. 2. Strokecenter.org. http://www.strokecenter.org/wp content/uploads/2011/08/barthel_index.pdf. Accessed March 1, 2013.
  12. 12. Majority of Ischemic Strokes Due to Atrial Fibrillation Present With Hemiplegia and Aphasia Proportion of patients (%) • 15% of patients with AFib-related stroke will present comatose1 Select stroke symptoms at presentation (p < 0.0001)2 80 60 67.9 AFib (n=6842) 59.9 50 No AFib (n=20,118) 40.4 40 14.3 20 11.8 17.3 12.3 0 Hemiplegia • Speech disturbances Visual disturbances Dysphagia 1 in 3 patients with AFib-related ischemic stroke at admission present1,3: • Unable to feed, bathe, or groom themselves • Bowel and bladder incontinent, unable to self-toilet • Immobile, unable to use stairs, unable to sit 1. Steger C et al. Eur Heart J. 2004;25:1734-1740. 2. Gattellari M et al. Cerebrovasc Dis. 2011;32:370-382. 3. Strokecenter.org. http://www.strokecenter.org/wp content/uploads/2011/08/barthel_index.pdf. Accessed March 1, 2013.
  13. 13. Time Is Brain in Acute Ischemic Stroke • Once an ischemic stroke has happened, timely management is critical for ensuring the best possible outcome1-3 Potential Estimated Rate of Loss in Untreated Acute Ischemic Stroke4 Per Second Per Hour Per Stroke (~10 hr) ~32,000 neurons lost 1.9 million neurons lost 120 million neurons lost 1.2 billion neurons lost ~233 million synapses lost 14 billion synapses lost 830 billion synapses lost 8.3 trillion synapses lost ~218 yards of fibers lost 7.5 miles of fibers lost 447 miles of fibers lost 4470 miles of fibers lost Accelerated aging: 8.7 hours 1. 2. 3. 4. Per Minute Accelerated aging: 3.1 weeks Accelerated aging: 3.6 years Accelerated aging: 36 y Jauch EC et al. Stroke. 2013;44:870-947. Fonarow GC et al. Circulation. 2011;123:750-758. Hacke W et al. Lancet. 2004;363:768-774. Saver JL. Stroke. 2006;37:263-266.
  14. 14. Patients With Atrial Fibrillation-Related Ischemic Strokes Are More Likely to Have Complications in the Hospital Complications During Hospital Stay for Acute Ischemic Stroke 50 43.1 Proportion of patients (%) 45 40 35 30.8 AFib (n=6842) 30 No AFib (n=20,118) 25 20 15 10 14.7 14.6 11.6 5.9 8.4 11.4 10.5 7.5 5 0 Mechanical vent/ICU/coma (p<0.0001) Pneumonia (p<0.0001) Gattellari M et al. Cerebrovasc Dis. 2011;32:370-382. Urinary incontinence (p<0.0001) Urinary tract infection (p<0.0001) Any complication (p<0.0001)
  15. 15. Patients With Ischemic Strokes Due to Atrial Fibrillation Are More Likely to Be Disabled at Discharge and Less Likely to Be Discharged to Home • At discharge, patients with AFib-related ischemic stroke are more disabled than patients without AFib1-3* – Less able to perform self-care or activities of daily living – More likely to be dependent Percent of patients (%) Percentage of patients discharged home1,4 70 60 50 40 30 20 10 0 27% fewer 32% fewer 60 44 AFib 66.4 45.1 No AFib Steger et al (n=992)* † Kimura et al (n=15,831) *Patients with AFib were older, more likely to be female, have a history of stroke, CAD, and heart disease. 1 †Patients with AFib were older, more likely to be female, and have a history of stroke. 4 1. Steger C et al. Eur Heart J. 2004;25:1734-1740. 2. Strokecenter.org. http://www.strokecenter.org/wp-content/uploads/2011/08/modified_rankin.pdf. Accessed March 1, 2013. 3. Strokecenter.org. http://www.strokecenter.org/wp content/uploads/2011/08/barthel_index.pdf. Accessed March 1, 2013. 4. Kimura K et al. J Neurol Neurosurg Psychiatry. 2005;76:679-683.
  16. 16. Atrial Fibrillation-Related Ischemic Stroke Is Associated With Higher Short- and Long-Term Mortality Adjusted mortality in patients post-ischemic stroke1 Annual mortality rate post-ischemic stroke2 60 30 25 AFib (n=6842) 20.9 20 15 No AFib (n=20,118) 14.7 14.1 50 23.1 Annualized rate (%/yr) Proportion of patients (%) 26.7 10.9 10 AFib (n=869) 40 No AFib (n=2661) 30 20 5 10 0 0 30 day 90 day 1 year 1. Gattellari M et al. Cerebrovasc Dis. 2011;32:370-382. 2. Marini C et al. Stroke. 2005;36:1115-1119. 1 2 3 4 5 Years 6 7 8
  17. 17. Patients With Atrial Fibrillation-Related Ischemic Stroke Are More Likely to Remain Disabled Disability post-ischemic stroke 90 79.5 Mean Barthel Index score 80 79 70 80.3 64.3 58.6 60 49.7 50 46.1 40 29.6 30 AFib (n=30) 20 No AFib (n=120) 10 0 Acute 3 months 6 months 12 months Lin H-J et al. Stroke. 1996;27:1760-1764.
  18. 18. Patient Emotional and Psychological Phases Through Their Stroke* Evolution Acute Care Inpatient Rehabilitation Discharge Home • Focus on “getting better” & returning to pre-stroke life • Intensive therapy • Marked improvement • Present focused • Increased risk of injury • Loss of control/independence • Drastic decrease in treatment intensity • Reach a plateau in functional recovery • Increased “self” focus • Comparison between pre- & post-stroke life • Begin to realize long-term impact on functional status Stroke Survivors • Limited memory of this phase Phase 1 – Stroke Crisis Phase 2 – Expectations for Recovery Phase 3 – Crisis of Discharge *Not specific to AFib-related ischemic stroke. Used with permission. Lutz BJ, Young ME, Cox KJ, et al. The Crisis of Stroke: Experiences of Patients and Their Family Caregivers, Topics in Stroke Rehabilitation, 2011;18(6):189. www.strokejournal.com.
  19. 19. Transitioning Out of the Hospital After a Stroke* May Have Significant Emotional and Psychological Impact on Caregivers Phase 1 – Stroke Crisis • Crisis mode • No preparation • Focus on patient survival • Uncertain prognosis/future • Family support • Decision about rehabilitation Phase 2 – Expectations for Recovery Focus on recovery Expecting return to pre-stroke life • Begin to plan for & to try to anticipate post-discharge needs • Become overwhelmed with discharge preparation • Multiple competing demands Phase 3 – Crisis of Discharge • Realize the enormity of the caregiver role & need for help • 24/7 responsibility • Assume new roles/ responsibilities • Feel alone/abandoned/ isolated/overwhelmed • Become exhausted • Concern about survivor’s mental & physical health • Increased risk for injury & poor health • Increased concerns about financial impact • Loss/change in future plans Family Caregivers Increasing focus on & responsibility for patient’s needs Decreasing focus on self/own self-care *Not specific to AFib-related ischemic stroke. Used with permission. Lutz BJ, Young ME, Cox KJ, et al. The Crisis of Stroke: Experiences of Patients and Their Family Caregivers, Topics in Stroke Rehabilitation, 2011;18(6):189. www.strokejournal.com
  20. 20. Stroke Not Only Impacts Physical Symptoms, but Emotional as Well Meta-analysis of depression frequency post-stroke Phase/study Acute Population Hospital Rehabilitation Subtotal Proportional Frequency (95% CI) 33% (29% to 37%) 36% (0% to 73%) 30% (16% to 44%) 32% (19% to 44%) Medium-term Population Hospital Rehabilitation Subtotal 33% (0% to 72%) 32% (23% to 41%) 36% (20% to 39%) 34% (20% to 39%) Long-term Population Hospital Rehabilitation Subtotal 34% (24% to 43%) 34% (24% to 45%) 34% (26% to 42%) 34% (29% to 39%) Overall 33% (29% to 36%) 0 20 40 60 Percent 80 100 • As many as 1 in 3 stroke patients will report symptoms of depression, regardless of stroke etiology Used with permission from Hackett ML et al. Stroke. 2005;36:1330-1340.
  21. 21. Long-term Burden on Caregivers of Stroke Patients Can Be Significant • Study of 115 caregivers of stroke patients at least 3 years post-stroke. Caregivers were assessed for burden of caregiving (using Sense of Competence Questionnaire) and potential explanatory factors Items associated with high level of caregiver burden “I feel that my social life has suffered because of my involvement with my partner” “I worry all the time about my partner” “The responsibility for my partner weighs heavily on me over and above the responsibilities for my family, my job, etc” “It is unclear to me how much care my partner needs” “I feel that my partner seems to expect me to take care of him/her as if I were the only one he/she could depend on” Scholte op Reimer WJM et al. Stroke. 1998;29:1605-1611.
  22. 22. Management of Patients With Atrial Fibrillation
  23. 23. Atrial Fibrillation Management Is Multifactorial, Involving Rate/ Rhythm Control and Thromboprophylaxis Paroxysmal AFib Persistent AFib • No rate or rhythm • Anticoagulation as control unless needed indicated for significant • Rate control as needed symptoms if minimal or no • Anticoagulation as symptoms indicated • If disabling symptoms, • Consider ablation if consider pharmacologic antiarrhythmics fail therapy first, then direct current cardioversion if needed • Consider ablation if antiarrhythmics fail Fuster V et al. Circulation. 2011;123:e269-e367. Permanent AFib • Anticoagulation and rate control as needed
  24. 24. Ischemic Stroke Risk Is Similar Regardless of Rate/Rhythm Control or Pattern of Atrial Fibrillation Observed Rate of Ischemic Stroke by Rate or Rhythm Control1 Observed Rate of Ischemic Stroke by Risk Group and Type of AFib2 8 14 7.1 Annualized stroke rate, (%/yr) 7 Percent of patients, (%) (p= 0.79) 6 5.5 5 4 3 2 1 0 (p= NS) 12 Paroxysmal (n= 460) Sustained (n= 1552) 10 8 (p= NS) 6 4 (p= NS) 2 0 Rate Rhythm Low-Risk* Moderate-Risk† High-Risk‡ *No moderate or high-risk features. †Hypertension (systolic BP > 160 mm Hg or diastolic BP > 90 mm Hg) and age ≤ 75 years; diabetes (definition not indicated), and no high-risk features. ‡Age > 75 years and hypertension or female, prior stroke or TIA. 1. Wyse DG et al. N Engl J Med. 2002;347:1825-1833. 2. Adapted with permission from Hart RG et al. J Am Coll Cardiol. 2000;35:183-187.
  25. 25. CHADS2 and CHA2DS2-VASc Are Risk Stratification Schemes That Can Help Assess the Risk of Ischemic Stroke in Non-valvular Atrial Fibrillation Stroke risk stratification CHADS2 score1 Criteria CHA2DS2-VASc Score2 1 C CHF/LV dysfunction 1 1 H Hypertension 1 1 A Age ≥75 years 2 1 D Diabetes mellitus 1 2 S Stroke/TIA/TE 2 N/A V Vascular disease* 1 N/A A Age 65-74 years 1 N/A Sc Sex category (female gender) 1 Assessment of risk based on score2 0: Low risk 1: Intermediate risk ≥ 2: High risk *Includes prior myocardial infarction, peripheral artery disease, or aortic plaque. 2 1. Gage BF et al. JAMA. 2001;285:2864-2870. 2. Lip GYH et al. Chest. 2010;137:263-272.
  26. 26. HAS-BLED Is a Risk Stratification Scheme That Can Help Assess the Risk of Bleeding in Atrial Fibrillation HAS-BLED Scoring System1 Score Annualized rate of major bleeding in anticoagulated* patients with AFib2 18 Criteria 15.5 1 H Hypertension 1 or 2 A Abnormal renal and liver function (1 pt each) 1 S Stroke 1 B Bleeding 1 L Labile INRs Annualized rate (%/yr) 16 14 12 10 8 E Elderly 1 or 2 D Drugs or alcohol (1 pt each) 3.4 4 2 1 5.7 6 1.9 2.4 2 3 0.7 0 1 4 HAS-BLED score *48,599 patients with AFib on anticoagulation, does not include patients on anticoagulation + aspirin 1. Pisters R et al. CHEST. 2010;138:1093-1100. 2. Friberg L et al. Eur Heart J. 2012;33:1500-1510. 5 6
  27. 27. Anticoagulation Is Recommended to Reduce the Risk of Ischemic Stroke and Systemic Thromboembolism • ACCF/AHA/HRS Guidelines for Antithrombotic Therapy for Patients With AFib1* • For primary prevention of thromboembolism in patients with NVAF • Antithrombotic therapy with either aspirin or an anticoagulant is reasonable in patients with one moderate risk factor • Antithrombotic therapy is recommended for patients with more than 1 moderate risk factor • Anticoagulation is associated with an increased risk of bleeding, including hemorrhagic stroke. This risk must be weighed against the benefit of stroke risk reduction2,3 • Anticoagulation therapy has been shown to reduce the risk of ischemic stroke up to 2/3 (67%) vs control/placebo4 ACCF=American College of Cardiology Foundation; AHA=American Heart Association; HRS=Heart Rhythm Society *The American Heart Association is a voluntary national health agency to help reduce disability and death from cardiovascular disease and stroke. The full guidelines can be located online at: http://circ.ahajournals.org/content/123/10/e269. High-risk factors: prior thromboembolism (stroke, TIA, or systemic embolism) and mitral stenosis, prosthetic heart valve.1 Moderate-risk factors: age ≥75 years, hypertension, heart failure, LVEF ≤ 35%, and diabetes mellitus.1 Less validated risk factors: female gender, age 65-74 years, coronary artery disease, thyrotoxicosis.1 1. 2. 3. 4. Fuster V et al. Circulation. 2011;123:e269-e367. Hart RJ. Neurology. 2000;55:907-908. Fang MC et al. Stroke. 2012;43:1-5. Hart RJ et al. Ann Intern Med. 2007;146:857-867.
  28. 28. In Anticoagulation Risk-Benefit Assessment, the Risk of Events Must Be Weighed Against Their Relative Frequency and Severity Annual Event Rate1,2 Mortality at 30 Days2,3 Ischemic Stroke* CHADS2 score† 0: 0.6% 1: 3.4% 2: 4.7% 3: 8.0% 4: 12.6% 5: 14.1% 6: 14.6% 27.7% Intracranial Bleed 0.47% 48.6% Major Extracranial Bleed‡ 0.64% 5.1% Event *In patients not on anticoagulation. †Adjusted for aspirin use. ‡Major extracranial bleeding was defined as fatal, requiring transfusion of ≥2 units of packed red blood cells, or hemorrhage into a critical anatomic site. 1. Friberg L et al. Eur Heart J. 2012;33:1500-1510. 2. Fang MC et al. Am J Med. 2007;120:700-705. 3. Fang MC et al. Stroke. 2012;43:1793-1799.
  29. 29. Approximately 50% of Patients With Atrial Fibrillation Do Not Receive Anticoagulation Oral Anticoagulation Is Prescribed for Only 41% to 65% of Eligible Patients With AFib1-7 Patients Treated With Oral Anticoagulation, (%) 100 65 55 54 50 0 64 52 51 41 ATRIA1 N= 11,082 NABOR2 N= 945 Hylek3 N= 405 Medicare4 N= 17,272 Walker5 N= 116,969 ATRIA= Anticoagulation and Risk Factors in Atrial Fibrillation. NABOR= National Anticoagulation Benchmark and Outcomes Report. Williams6 Euro N= 50,071 Heart Study7 N= 2706 1. Go AS et al. Ann Intern Med. 1999;131:927-934. 2. Waldo AL et al. J Am Coll Cardiol. 2005;46:1729-1736. 3. Hylek EM et al. Stroke. 2006;37:1075-1080. 4. Birman-Deych E et al. Stroke. 2006;37:1070-1074. 5. Walker AM, Bennett D. Heart Rhythm. 2008;5:1365-1372. 6. Williams CJ et al. American College of Cardiology 58th Annual Scientific Session; March 29-31, 2009; Orlando, FL. 7. Nieuwlaat R et al. Eur Heart J. 2006;27:3018-3026.
  30. 30. Conclusions • AFib is a common cause of ischemic stroke that has devastating consequences for patients and families • AFib-related ischemic strokes can result in worse patient outcomes than those caused by other underlying etiologies • The risk of ischemic stroke remains regardless of the pattern of AFib or rate/rhythm intervention • Anticoagulating is critical to reducing the risk of AFibrelated ischemic strokes and yet it is underutilized • Use of anticoagulation should be weighed against the increased risk of bleeding AFIB574903PROF

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