Transcript Stroke - Anticoagulation Centers of Excellence
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
September 2012 - June 2013
Disclosure of Commercial Support
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
This activity is supported by educational grants from Boehringer Ingelheim Pharmaceuticals, Inc. and Bristol-Myers Squibb and Pfizer Inc. This slide presentation and artwork was independently developed by Boston University School of Medicine’s Powerpoint designer.
Boston University School of Medicine’s Disclosure Policy
Boston University School of Medicine asks all individuals involved in the development and presentation of Continuing Medical Education (CME) activities to disclose all relationships with commercial interests. This information is disclosed to CME activity participants. Boston University School of Medicine has procedures to resolve any apparent conflicts of interest. In addition, faculty members are asked to disclose when any unapproved use of pharmaceuticals and devices is being discussed. 2
Accreditation Information
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Boston University School of Medicine and Anticoagulation Forum. Boston University School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.
Boston University School of Medicine designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Continuing Nursing Education Provider Unit, Boston University School of Medicine is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.
CNE Contact Hours: 1.00
Nurses will receive contact hours for those sessions attended, after completion of an evaluation and claim for credit form.
Continuing Pharmacy Education Credits The University of Rhode Island College of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Attendance and completion of program evaluations at the conclusion of the program are required for a statement of credit. This knowledge-based activity is approved for 1.0 Contact Hours (0.1 CEUs). UAN: 0060-9999-12- 040-L01-P. Expiration date: September 5, 2013.
3
Learning Objectives
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
At the conclusion of this activity participants will be able to: : • Describe benefits of oral anticoagulants for stroke prevention in atrial fibrillation • Identify the population of patients who would be at risk of stroke with atrial fibrillation • Compare current and new oral anticoagulants with regards to safety, efficacy, pharmacology, cost and convenience • Compare the benefits and risks of oral anticoagulant therapy for reducing the risk of stroke in atrial fibrillation patients • Utilize available decision making tools to stratify the risks and benefits of anticoagulation therapy in patients with atrial fibrillation 4
Highlights
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
• Prevalence and incidence of AF • Risk stratification for stroke and bleeding • New oral anticoagulants • Guidelines • Practical considerations for choosing an anticoagulant
Highlights
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
•
Prevalence and incidence of AF
• Risk stratification for stroke and bleeding • New oral anticoagulants • Guidelines • Practical considerations for choosing an anticoagulant
Question #1
An 82 year old man is in your office for an annual Medicare physical. What is the chance he has atrial fibrillation?
1.
2.
3.
4.
1% 5% 10% 25% 7
Prevalence of Diagnosed AF
Stratified by Age and Sex
12.0
10.0
Women Men
10.3
9.1
11.1
8.0
7.3
7.2
6.0
5.0
4.0
3.4
3.0
2.0
0.1
0.2
0.4
0.9
1.0
1.7
1.7
0.0
<55 55-59 60-64 65-69 70-74 # Women # Men 530 1529 310 634 566 934 896 1426 1498 1907
Go AS, JAMA. 2001 May 9;285(18):2370-5. Pub Med PMID: 11343485
5.0
75-79 1572 1886 80-84 1291 1374 > 85 1132 759
x-axis = % y-axis = # of men/women 8
Question #2
A 46 year old male patient is in for an annual physical exam. What is his lifetime risk of developing AF?
1.
2.
1% 5% 3.
4.
10% 25% 9
Incidence of AF
Lifetime Risk for AF at Selected Index Ages by Sex
Index Age, yrs 40 50 60 70 80 26.0% 25.9% 25.8% 24.3% 22.7% Men
(24.0 – 27.0) (23.9 – 27.0) (23.7 – 26.9) (22.1 – 25.5) (20.1 – 24.1)
23.0% Women
(21.0 – 24.0)
23.2% 23.4%
(21.3 – 24.3) (21.4 – 24.4)
23.0% 21.6%
(20.9 – 24.1) (19.3 – 22.7)
1 in
Men & women >40 Years
4
will develop AF Lifetime risk if currently free of AF Lloyd-Jones DM, et al. Circulation. 2004 Aug 31;110(9):1042-6. Pub Med PMID: 15313941.
10
Highlights
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
• Prevalence and incidence of AF •
Risk stratification for stroke and bleeding
• New oral anticoagulants • Guidelines • Practical considerations for choosing an anticoagulant
Question #3
68 year old female with atrial fibrillation and no other co morbidities. How would you classify her stroke risk?
1.
2.
3.
Low Moderate High 12
Scoring Systems in Atrial Fibrillation
• Given that anticoagulant therapy has both risks (principally bleeding) and benefits (a reduced risk of thrombosis) many authors have attempted to produce scoring systems which estimate the risks of these outcomes • No one scoring system is universally accepted or highly predictive (in individual patients) 13
Scoring Systems in Stroke Risk
• A variety of systems have been published – Outlined on next slide • All use selected clinical characteristics to predict the risk of stroke • Most widely used is the CHADS 2 score • All scores provide a rough estimate of risk of thrombosis in a population at similar risk as patient being reviewed 14
Atrial Fibrillation Risk Stratification
12 Schemes applied to 1000 patients from SPAF III study
High Moderate Low
Stroke Risk in Atrial Fibrillation Working Group. Stroke. 2008 Jun;39(6):1901-10. Pub Med PMID: 18420954. 15
CHADS
2
: Risk of Stroke
National Registry of Atrial Fibrillation Participants (NRAF)
CHADS 2 Score 0 # Patients (n = 1733) 120 # Strokes (n = 94) 2 NRAF Crude Stroke Rate per 100 Patient-yrs 1.2
NRAF Adjusted Stroke Rate
(95% CI)†
1.9
(1.2-3.0)
3 4 1 2 463 523 337 220 17 23 25 19 2.8
3.6
6.4
8.0
2.8 4.0 5.9
8.5
(2.0-3.8) (3.1-5.1) (4.6-7.3) (6.3-11.1)
5 65 6 7.7
12.5
(8.2-17.5)
6 5 2 44.0
18.2
(10.5-27.4)
Scoring:
1 point: Congestive heart failure, HTN, < 75 years, and DM 2 points: Stroke history or transient ischemic attack † Expected stroke rate per 100 pt-yrs from the exponential survival model, assuming aspirin not taken Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. JAMA. 2001 Jun 13;285(22):2864-70. Pub Med PMID: 11401607.
16
CHA
2
DS
2
-VASc
2009 Birmingham Schema Expressed as a Point-Based Scoring System
Risk Factor C ongestive heart failure/LV dysfunction H ypertension A ge ≥ 75 y D iabetes mellitus S troke/TIA/TE V ascular disease
(prior myocardial infarction, peripheral artery disease, or aortic plaque)
A ge 65-74 y S ex c ategory
(i.e. female gender)
LV = left ventricular; TE = thromboembolism
Score 1 1 2 1 2 1 1 1
Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Chest. 2010 Feb;137(2):263-72. Pub Med PMID: 19762550. 17
CHA
2
DS
2
-VASc
Stroke or Other TE at One Year
CHA 2 DS 2 VASc Score 0 1 6 7 2 3 4 5 # 103 162 184 203 208 95 57 25 #TE Events 0 1 2 2 3 8 4 3 TE Rate During 1 yr (95% CI) 0%
(0-0)
0.6%
(0.0-3.4)
1.6%
(0.3-4.7)
3.9%
(1.7-7.6)
1.9%
(0.5-4.9)
3.2%
(0.7-9.0)
3.6%
(0.4-12.3)
8.0%
(1.0-26.0)
TE Rate During 1 yr, Adjusted for Aspirin RX 0% 0.7% 1.9% 4.7% 2.3% 3.9% 4.5% 10.1% 8 9 9 1 1 1 11.1% 100%
(0.3-48.3) (2.5-100)
14.2% 100% Total 1,084 25
P Value for trend 0.003
Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Chest. 2010 Feb;137(2):263-72. Pub Med PMID: 19762550. 18
CHA
2
DS
2
-VASc and CHADS
2
Score 0
Refines stroke risk stratification in AF patients: nationwide cohort
–1
1 Year Follow-up 12 Years Follow-up Person Yrs Events Stroke rate (95%CI) Person Yrs Events Stroke rate (95%CI) CHADS 2 score 0 –1
40,272 1,405 3.49 (3.31
–3.68) 187,200 4,599 2.46 (2.39
–2.53) CHA 2 DS 2 -VASc = 0 6,919 58 0.84 (0.65
–1.08) 39,500 299 0.76 (0.68
–0.85) CHA 2 DS 2 -VASc = 1 8,880 159 1.79 (1.53
–2.09) 45,926 662 1.44 (1.34
–1.56) CHA 2 DS 2 -VASc = 2 11,863 435 3.67 (3.34
–4.03) 51,595 1,489 2.89 (2.74
–3.04) CHA 2 DS 2 -VASc = 3 11,473 660 5.75 (5.33
–6.21) 45,799 1,933 4.22 (4.04
–4.41) CHA 2 DS 2 -VASc = 4 1,137 93 8.18 (6.68
–10.02) 4,380 216 4.93 (4.32
–5.64)
CHADS 2 score = 0 17,327 275 1.59 (1.41
–1.79) 92,531 1182 1.28 (1.21
–1.35) CHA 2 DS 2 -VASc = 0 6,919 58 0.84 (0.65
–1.08) 39,500 299 0.76 (0.68
–0.85) CHA 2 DS 2 -VASc = 1 6,811 119 1.75 (1.46
–2.09) 35,079 504 1.44 (1.32
–1.57) CHA 2 DS 2 -VASc = 2 3,347 90 2.69 (2.19
–3.31) 16,710 353 2.11 (1.90
–2.34) CHA 2 DS 2 -VASc = 3 250 8 3.20 (1.60
–6.40) 1,242 26 2.09 (1.43
–3.07) CHADS 2 Score = 1
22,945 1,130 4.92 (4.65
–5.22) 94,669 3417 3.61 (3.49
–3.73) CHA 2 DS 2 -VASc = 1 2,069 40 1.93 (1.42
–2.64) 10,847 158 1.46 (1.25
–1.70) CHA 2 DS 2 -VASc = 2 8,516 345 4.05 (3.65
–4.50) 34,885 1136 3.26 (3.07
–3.45) CHA 2 DS 2 -VASc = 3 11,223 652 5.81 (5.38
–6.27) 44,557 1907 4.28 (4.09
–4.48) CHA 2 DS 2 -VASc = 4 1,137 93 8.18 (6.68
–10.02) 4,380 216 4.93 (4.32
–5.64) Olesen JB, Torp-Pedersen C, Hansen ML, Lip GY. Thromb Haemost. 2012 Jun;107(6):1172-9. Pub Med PMID: 22473219.
19
Question #4
78 year old male with atrial fibrillation and hypertension (CHADS2 score = 2 [4% stroke rate per year]). What is his annual major bleeding rate?
1.
1% 2.
3.
2% 3% 4.
5.
5% 10% 20
Bleeding Risk Scores
• Variety of scoring systems developed to predict risk of bleeding in patients initiating anticoagulants, as with stroke risk • Less predictive than stroke risk scores, in general • Each score incorporates clinical characteristics and provides estimate of risk of bleeding in a population similar to patients being considered • Unclear whether to include risk scores in decision making for individual patients 21
Bleeding Risk Scores Widely Used in AF
•
HAEMORRHAGES
1 •
HASBLED
2 •
ATRIA Score
3 1.
Gage BF, et al. Am Heart J. 2006 Mar;151(3):713-9. PMID: 16504638. Pub Med PMID:16504638.
2.
Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. Chest. 2010 Nov;138(5):1093-100. PMID:20299623.
3.
Fang MC, et al. J Am Coll Cardiol. 2011 Jul 19;58(4):395-401. Pub Med PMID:21757117.
22
Bleeding Risk Scores in AF
ATRIA Anemia 1 3 HAS-BLED H ypertension 4 1 HEMORR 2 HAGES H epatic 10 or Renal disease 2 Severe renal disease 2 Age ≥75 yrs Any prior hemorrhage Hypertension 3 3 2 1 1 A bnormal Renal 5 Liver function 6 or S B L troke leeding abile INR 8 1 1 1 1 1 E thanol abuse M alignancy O lder Age (>75 yrs) R educed platelet number or function 11 E lderly (>65 yrs) 1 R ebleeding 12
Hemoglobin <13 g/dl men; <12 g/dl women Estimated glomerular filtration rate <30 ml/min or dialysis-dependent
D rugs 9 Alcohol or
1.
2.
3.
4.
5.
6.
8.
9.
in association with aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase >3 x upper limit normal, etc.) Unstable/high INRs or poor time in therapeutic range (eg <60%) Concomitant use of drugs, such as antiplatelet agents, non-steroidal anti-inflammatory drugs, or alcohol abuse etc. 10. Cirrhosis, two-fold or greater elevation of AST or APT, or albumin <3.6 g/dl 11. Platelets <75,000, use of antiplatelet therapy (eg daily aspirin) or NSAID therapy; or blood dyscrasia 12. Prior hospitalization for bleeding 13. Most recent hematocrit <30 or hemoglobin <10 g/dl 14. CYP2C9*2 and/or CYP2C9*3 15. Alzheimer's dementia, Parkinson's disease, schizophrenia, or any condition predisposing to repeated falls
1 1
Diagnosed hypertension Systolic blood pressure >160 mmHg Presence of chronic dialysis or renal transplantation or serum creatinine ≥200 mmol/L Chronic hepatic disease (eg cirrhosis) or biochemical evidence of significant hepatic derangement (eg bilirubin 2 x upper limit of normal,
H A G E S ypertension nemia troke 13 4 enetic factors 14 xcessive fall risk 15
Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. J Am Coll Cardiol 2012;60:000 –000. 2012 Jul 24. [Epub ahead of print] Online Appendix. PMID: 22858389.
1 1 1 1 1
23
1 1 1 2 1 1 1
AMADEUS Cohort
Stratified by the HEMORR 2 HAGES, HAS-BLED, and ATRIA Schemes
All Patients Clinically Relevant Bleeding Major Bleeding Scheme HEMORR 2 HAGES Low (≤1) Risk Intermediate Risk (2 –3) High Risk (>3) TOTAL HAS-BLED Low Risk (<3) High Risk ( ≥3) TOTAL ATRIA Low Risk (<4) Intermediate Risk (4) High Risk (>4) TOTAL 1,738 (76.6) 517 (22.8) 13 (0.5) 2,268 1,739 (75.9) 553 (24.1) 2,292 2,038 (90) 102 (4.4) 128 (5.6) 2,268 182 (10.5) 63 (12.2) 3 (23.1) 248 (10.9) 159 (9.1) 92 (16.6) 251 (11.0) 220 (10.8) 13 (12.7) 18 (14.1) 248 (10.9) 25 (1.4) 13 (2.5) 1 (7.7) 39 (1.7) 22 (1.3) 17 (3.1) 39 (1.7) 31 (1.5) 3 (2.9) 5 (3.9) 39 (1.7)
Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. J Am Coll Cardiol 2012;60:000 –000. 2012 Jul 24. [Epub ahead of print] Online Appendix. PMID: 22858389.
24
Risks of Bleeding with Warfarin or Dabigatran in AF
Oldgren J, et al. Ann Intern Med. 2011 Nov 15;155(10):660-7, W204. Pub Med PMID: 22084332.
25
Adjusted HR for Death After Stroke, MI, or Major Hemorrhage
In Patients Who Received Antiplatelet Therapy in the ACTIVE Trials
Event Pts With Event, n Subsequent Deaths
,
n
(Adjusted Rate)
HR for Death (95% CI)† Relative Weights‡ Ischemic stroke Hemorrhage stroke Subdural hemorrhage Major extracranial bleeding event Myocardial infarction
† Compared to no event ‡ ratio of hazard ratios
785 59 42 435 260 362 (36.4) 48 (81.4) 15 (32.4) 162 (31.6) 120 (38.9) 5.74
(5.10 – 6.47)
1.00
(reference)
17.67
(13.15 – 23.75)
3.44
(2.06 – 5.74)
3.08
0.60
3.82
(3.24 – 4.51)
5.44
(4.51 – 6.56)
0.67
0.95
Connolly SJ, et al. Ann Intern Med. 2011 Nov 1;155(9):579-86. Pub Med PMID: 22041946.
26
Highlights
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
• Prevalence and incidence of AF • Risk stratification for stroke and bleeding •
New oral anticoagulants
• Guidelines • Practical considerations for choosing an anticoagulant
Pharmacokinetics of NOACs
Direct factor inhibition Bioavailability (F rel ) Peak action (t max ) Protein binding Renal clearance Elimination half life with creatinine clearance > 80 ml/min Elimination half life with creatinine clearance 50 –79 ml/min Elimination half life with creatinine clearance 30 –49 ml/min Elimination half life with creatinine clearance < 30 ml/min Apixaban Xa 80% 1 –3 hr 84% 25% 15.1 hr 14.6 hr 17.6 hr 17.3 hr Dabigatran IIa 6% 1 –3 hr 35% 80% 13.8 hr 16.6 hr 18.7 hr 27.5 hr Rivaroxaban Xa 80% 1 –3 hr 92 –95% 33% 8.3 hr 8.7 hr 9.0 hr 9.5 hr
Kaatz S, et al. Am J Hematol. 2012 May;87 Suppl 1:S141-5. Pub Med PMID: 22473649.
28
Measuring the Effect of NOACs
Coagulation Assays PT -dilute PT -modified PT aPTT TT -dTT/HEMOCLOT Chromogenic Assays -Anti-Xa -Anti-Iia
n/a = not available
Apixaban Not useful Data n/a Qualitative Not useful No effect No effect Rivaroxaban Qualitative Data n/a Data n/a Not useful No effect No effect Dabigatran Not useful Data n/a Data n/a Qualitative Qualitative Quantitative Quantitative No effect Quantitative No Effect No effect Quantitative
Garcia DA, et al. In review.
29
Reversal of NOACs
Types of Studies Evaluating Reversal of New Oral Anticoagulants
Oral activated charcoal Hemodialysis Hemoperfusion with activated charcoal Fresh frozen plasma Activated factor VIIa 3-factor PCC 4-factor PCC Apixaban No data No data No data No data No data No data No data Dabigatran Rivaroxaban In vitro Human volunteers In vitro Mouse model Rat model No data Human volunteers and rat model No data No data No data No data Rat and baboon model No data Human volunteers
Kaatz S, et al. Am J Hematol. 2012 May;87 Suppl 1:S141-5. Pub Med PMID: 22473649.
30
Reversal of NOACs
Suggestions for Reversal of New Oral Anticoagulants
Oral activated charcoal Hemodialysis Hemoperfusion with activated charcoal Fresh frozen plasma Activated factor VIIa 3-factor PCC 4-factor PCC Apixaban Yes No Possible No Unclear Unclear Possible Dabigatran Yes Yes Yes No Unclear Unclear Possible Rivaroxaban Yes No Possible No Unclear Unclear Possible
Kaatz S, et al. Am J Hematol. 2012 May;87 Suppl 1:S141-5. Pub Med PMID: 22473649.
31
Meta-analysis of Efficacy and Safety of New Oral Anticoagulants
Dabigatran, Rivaroxaban, Apixaban vs. Warfarin in AF patients
All cause stroke/SEE Ischemic and unspecified stroke Hemorrhagic stroke
Meta-analysis of Efficacy and Safety of New Oral Anticoagulants
Dabigatran, Rivaroxaban, Apixaban vs. Warfarin in AF patients
Major bleeding Intracranial bleeding GI Bleeding
Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ. Am J Cardiol. 2012 Aug 1;110(3):453-60. Pub Med PMID: 22537354.
33
Highlights
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
• Prevalence and incidence of AF • Risk stratification for stroke and bleeding • New oral anticoagulants •
Guidelines
• Practical considerations for choosing an anticoagulant
Question #5
78 year old female with atrial fibrillation, hypertension and CHF. CHADS 2 = 3 CHA 2 DS 2 -VASc = 5 HAS-BLED = 2 What would you use for stroke prevention?
1.
No anti-thrombotics 2.
Aspirin 3.
4.
5.
Aspirin + clopidogrel VKA antagonist Dabigatran or Rivaroxaban 35
European Society of Cardiology Guidelines
CHA 2 DS 2 -VASc and Stroke Rate
Risk Factors For Stroke and Thrombo-embolism in Non-valvular AF Risk Factor Score C
ongestive heart failure/LV dysfunction*
H
ypertension*
A
ge >75**
D
iabetes Mellitus*
S
troke / TIA / Thrombo-embolism**
V
ascular Disease*
A
ge 65-74*
S
ex category (i.e. female sex)* Maximum Score Note: maximum score is 9 since age may contribute 0,1, or 2 points
* ‘Clinically relevant non-major’ risk factor ** “Major” risk factor
1 1 2 1 2 1 1 1 9 Camm AJ. Europace. 2010 Oct;12(10):1360-420. Pub Med PMID: 20876603.
36
European Society of Cardiology Guidelines
Approach to Thromboprophylaxis in Patients with AF
Risk Category
One ‘major’ risk factor
or
> 2 ‘clinically relevant non major’ risk factors One ‘clinically relevant non major’ risk factor’
CHA 2 DS 2 -VASc Score
> 2 1 No risk factors 0
Recommended Antithrombotic Therapy
OAC
1
• Either OAC or aspirin 75-325 mg daily • Preferred: OAC rather than aspirin • Either aspirin 75-325 mg daily or no antithrombotic therapy • Preferred: no antithrombotic therapy rather than aspirin
Risk of Bleeding
Low risk Measurable risk, or 1 clinically relevant non-major risk factor
HAS-BLED Score
0 –2 ≥3 1. Camm AJ. Europace. 2010 Oct;12(10):1360-420. Pub Med PMID: 20876603.
2. Connolly SJ, et al. N Engl J Med 2009;361:1139 –1151. PMID: 19717844.
Dabigatran Dosage 2
150 mg b.i.d.
110 mg b.i.d. 37
2011 ACCF/AHA/HRS Guidelines
Antithrombotic Therapy for Patients with Atrial Fibrillation
Risk Category 1 No risk factors Recommended Therapy Aspirin, 81 to 325 mg daily One moderate risk factor Any high risk factor or > 1 moderate-risk factor Aspirin, 81 to 325 mg daily, or warfarin (INR 2.0 to 3.0, target 2.5) Warfarin (INR 2.0 to 3.0, target 2.5)* Less Validated / Weaker Risk Factors Female gender Age 65 to 74 years 1 Coronary artery disease Thyrotoxicosis Moderate Risk Factors Age >75 years Hypertension Heart failure LV ejection fraction <35% Diabetes mellitus High Risk Factors Previous stroke, TIA or embolism Mitral stenosis Prosthetic heart valve*
* If mechanical valve, target international normalized ratio (INR) > 2.5
2011 Focused Update Recommendation Class I 2
Dabigatran is useful as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal to permanent AF and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance <15 mL/min) or advanced liver disease (impaired baseline clotting function).
(Level of Evidence: B)
1. Fuster V. Circulation. 2011 Mar 15;123(10): Pub Med PMID: 21382897.
2. Wann LS, et al. J Am Coll Cardiol. 2011 Mar 15;57(11):1330-7. Pub Med PMID: 21324629.
Comments
New Recommendation 38
ACCP Guidelines
For patients with Nonrheumatic AF, including those with Paroxysmal AF
Level of Risk Low Risk (CHADS 2 = 0) ACCP Recommendation No Therapy Intermediate Risk (CHADS 2 = 1) High Risk (CHADS 2 = 2) Oral anticoagulation Oral anticoagulation (dabigatran 150 mg b.i.d. vs. VKA**) Alternative* Aspirin Not Recommended Oral anticoagulation or combination therapy with aspirin and clopidogrel Aspirin Aspirin with clopidogrel Aspirin with clopidogrel Aspirin
*For patients with AF unsuitable for, or who refuse, oral anticoagulant (for reasons other than concerns about major bleeding) **VKA = adjusted-dose vitamin K antagonist You JJ, et al. Chest. 2012 Feb;141(2 Suppl):e531S-75S. Pub Med PMID: 22315271.
39
Canadian Cardiovascular Society Guidelines
Assess Thromboembolic Risk (CHADS 2 ) CHADS 2 = 0 CHADS 2 = 1 CHADS 2 = 2 Increasing stroke risk No anti thrombotic OAC* OAC No additional risk factors for stroke Either female sex or vascular disease Age > 65 yrs or combination female sex and vascular disease *ASA is a reasonable alternative for some as indicated by risk/benefit
When OAC therapy is indicated, most patients receive: • Dabigatran, rivaroxaban, or apixaban (after Health Canada approval) • • In preference to warfarin
Conditional Recommendation, High-Quality Evidence
Skanes AC, et al. Can J Cardiol. 2012 Mar-Apr;28(2):125-36. Pub Med PMID: 22433576.
40
Highlights
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
• Prevalence and incidence of AF • Risk stratification for stroke and bleeding • New oral anticoagulants • Guidelines •
Practical considerations for choosing an anticoagulant
Optimal Candidates for New Drugs
Patients who: • Find
INR testing burdensome
• Despite adherence to provider recommendations, have
low ‘time-in-range’
• Can
afford
(or arrange to get) the new drugs • Have
normal renal function
42
Optimal Candidates for Warfarin
Patients who: • Have (borderline)
renal insufficiency
• Are
taking stable dose of warfarin
and do not find INR testing burdensome • Have
access to self-testing
machine • Are concerned about the
lack of
an evidence-based
reversal
strategy 43
TTR per Country in RELY
90 80 70 60 50 44 47 48 49 49 53 53 54 55 55 56 56 56 57 58 58 60 60 62 62 64 64 64 64 64 65 65 66 66 66 67 68 68 70 70 70 71 71 72 72 72 74 74 77 40 30 20 10 0
Wallentin L, et al. Lancet. 2010 Sep 18;376(9745):975-83. PMID: 20801496.
USA: Improvement Needed
44
Stroke and Systemic Embolism
By Center TTR in RELY Wallentin L, et al. Lancet. 2010 Sep 18;376(9745):975-83. Pub Med PMID: 20801496.
• TTR=optimum therapeutic range • cTTR=center's mean TTR 45
Major Bleeding
By Center TTR in RELY Wallentin L, et al. Lancet. 2010 Sep 18;376(9745):975-83. PMID: 20801496.
• TTR=optimum therapeutic range • cTTR=center's mean TTR 46
Stroke and Systemic Embolization by Center Proportion of INR in Therapeutic Range in ROCKET AF
Center TTR‡ Rivaroxaban Total 45/1735 (2.59) Event Rate (100 Pt Yrs) § 1.77
Total Warfarin 62/1689 (3.67) Event Rate (100 Pt Yrs) § 2.53
0.00-50.6% 50.7%-58.5% 58.6-65.7% 53/1746 (3.04) 54/1734 (3.11) 1.94
1.90
63/1807 (3.49) 62/1758 (3.53) 2.18
2.14
65.7-100.0% 37/1676 (2.21) 1.33
55/1826 (3.01)
N=7061 rivaroxaban N=7082 warfarin P value for interaction=0.736
Time in therapeutic range-2-3 inclusive ‡Center TTR calculated using total INR values in target range from all warfarin subjects within center, divided by total INR values from all warfarin subjects within center §Number of events per 100 patient-years of follow-up II Hazard ratio from Cox proportional hazard model with treatment as a covariate
1.80
Rivaroxaban vs. Warfarin Hazard Ratio (95% CI)II 0.70 (0.48, 1.03) 0.89 (0.62, 1.29) 0.89 (0.62, 1.28) 0.74 (0.49, 1.12)
Patel MR, et al. N Engl J Med. 2011 Sep 8;365(10):883-91. Pub Med PMID: 21830957.
47
Summary
PREVENTING
Atrial Fibrillation Related
STROKES
with Anticoagulants
• Prevalence and incidence of AF • Risk stratification for stroke and bleeding • New oral anticoagulants • Guidelines • Practical considerations for choosing an anticoagulant 48