Stroke prevention in atrial fibrillation: defining the degree of - - PowerPoint PPT Presentation

• K. Butcher, MD, PhD, FRCP(C)

University of Alberta WMC Health Sciences Centre

Stroke prevention in atrial fibrillation: defining the degree of under treatment (Or Why AF is a Neurological Disease) ACC Rockies Banff, AB March 18, 2013

Disclosures and Acknowledgements

Speaker’s /Adivosry Board Honoraria Boeringher Ingelheim Bayer BMS/Pfizer Octapharma

Grant-in-Aid Salary Award Grant-in-Aid Grant-in-Aid Salary Award Grant-in-Aid Salary Award Salary Award

Outline

• AF is under-diagnosed
• Anticoagulation is under-utilized
• NOACs are under-utilized

Acute Stroke Diagnosis

ICH (15%) Ischemic Infarct (85%)

Lacunar Infarcts (LACI) Cortical Infarcts (PACI)

Investigating Stroke/TIA Mechanism

Lipohyalinosis Artery-artery Embolism Cardioembolism

Stroke Mechanism Frequency

Ischemic stroke 85- 88% Hemorrhagic stroke 12- 15%

Other 5% Cryptogenic 30% Cardiogenic embolism 20% Small vessel disease “lacunes” 25% Atherosclerotic cerebrovascular disease 20%

Albers GW, et al. Chest 2004; 126 (3 Suppl): 438S–512S McGrath et al. Stroke 2012; 43: 2048-2054. .

49 year old Male: Cryptogenic Stroke

• Normal TEE (no

LA enlargement)

• Normal 24 H

Holter x 2 (no atrial ectopy)

• Normal

Hypercoagulable Screen DWI CTA

82 year old Female: Cryptogenic Stroke??

• Carotid Doppler:

No atherosclerotic plaque

• TTE:

LAA Enlargement

• Holter:

Frequent PACs/atrial ectopy

DWI

Cardioembolic Stroke: A Growth Industry

Age- and Sex-Adjusted Incidence of AF in 1995-2000 Projected Number of Persons With AF in the United States Between 2000 and 2050

Millions Year

Miyasaka Circulation 2006;114:119

Cardioembolic Stroke

Typical Cardio-embolic Infarcts

Worse Prognosis Following Cardioembolic Stroke

8% 30% 1.4%

0% 5% 10% 15% 20% 25% 30% 35%

Small Vessel Large Vessel Cardioembolic One Year Risk of Death

Gladstone DJ et al. Stroke 2009; 40:235-240

Transient Left Hemiparesis

ICA Plaque

Transient Left Hemiparesis

Cardioembolic Pattern of Infarction (Paroxysmal AF later confirmed)

Next Investigation?

Cortical Ischemic Stroke (Embolic Pattern)

Echocardiography Options

Transthoracic Echocardiogram Transesophageal Echocardiogram

Higher Yield Cardiac Investigations

Holter Monitor Implantable Event Recorders External Event Recorder (SpiderFlash)

Infarct Load Predicts Holter Yield

Silent Infarct

% of Patients with Paroxysmal Atrial Fibrillation on Holter Number of Imaging Identified Infarcts

1 2 3 4 1 2 3 4 5 6 7

Holter Yield Increases with Ischemic Lesion Load:

EMBRACE Study

Repeat Holter Monior n=285 Accuheart Electrode Belt (30 days) n=287 Stroke/TIA and 1 negative Holter n=572 AF Detection: 3% AF Detection: 16%

Gladstone et al, 2013

Stroke Patients: Brief Paroxysmal AF

Number of Patients

• 1 point for Congestive Heart

Failure

• 1 point for Hypertension
• 1 point for Age ≥ 75 years
• 1 point for Diabetes Mellitus
• 2 points for Prior Stroke
• r TIA

AF Risk Stratification: CHADS2 Score

Gage BF, et al. JAMA. 2001;285:2864-2870

CHADS2 Score* Stroke rate

1.9 (1.2 -3.0) 1 2.8 (2.0-3.8) 2 4.0 (3.1-5.1) 3 5.9 (4.6-7.3) 4 8.5 (6.3 -11.1) 5 12.5 (8.2-17.5) 6 18.2 (10.5-17.4)

*Score 0: Patients can be administered aspirin *Score 1: Patients can be on aspirin and anticoagulant therapy *Score ≥2: Patients should be on anticoagulant therapy

29 year old male, lone AF, on ASA

Under-treatment of AF in Canada

no antithrombotics , 29% warfarin - therapeutic, 10% warfarin - subtherapeutic, 29% single antiplatelet agent, 29% dual antiplatelet therapy, 2%

Gladstone et al. Stroke 2009

Under-treatment in Edmonton

Patients with a known history of AF presenting with stroke/TIA to UAH 2012-13

Known AF + Stroke (Secondary Prevention)

25% 3% 15% 18% 39%

Warfarin Sub- therapeutic Warfarin therapeutic No antithrombotics Dual antiplatelet therapy Single antiplatelet agent

Gladstone et al. Stroke 2009

INR Control and Stroke Risk

Hylek EM et al. Ann Intern Med. 1994;120:897-902 Hylek EM et al. N Engl J Med. 1996;335:540-546.

INR ‘Control’

g

Ischemic Stroke

INR ‘Control’ 90 Male, TIA

Ischemic Stroke

INR Control: Clinical Trials vs. Clinical Practice

INR control is an ongoing challenge in routine clinical practice

RCT: Kalra et al. BMJ 2000 Matchar et al. Am J Med 2002 Bungard et al. Pharmacotherapy 2000

25 45 38 66 44 37 9 18 18 % of eligible patients receiving warfarin

Anticoagulant Associated ICH

3 h 6 h

INR=2.4

INR 3.1: Management Options?

• 1. Vitamin K 5 mg PO
• 2. FFP 1 unit IV – INR not re-checked

3 hours later: patient now hemiplegic, GCS 15

Management Continued

FFP 2 units IV -- INR 2.8

4 hours later

Management Continued

Transfer to tertiary centre FFP 4 units IV -- INR 1.0

Prothrombin Complex Concentrates (PCC)

• Blood Product
• Factors II, VII, IX, X
• Indicated for Vitamin K

Antagonist associated hemorrhage

40 ml-80 ml Octaplex (1000-2000 IU Factor IX activity). Dose varies with INR. and 10 mg Vitamin K Oral / IV

CT to Needle Time: 59 minutes

16:11, INR=3.3 PCC at 17:10, repeat INR=1.4 23 hour f/u scan

Recent Oral Anticoagulation Trials: Hemorrhagic Stroke

Apixaban not yet approved in Canada for stroke prevention in patients with atrial fibrilliation

The new oral anticoagulants are consistently associated with a numerically lower risk of hemorrhagic stroke compared with warfarin†

Data obtained from intention-to-treat analysis

†Not intended as cross-trial comparison

1. Connoly SJ, et al. N Engl J Med 2009;361:1139-1151. 2. Patel MR, et al. N Engl J Med 2011;365:883-891. 3. Granger C, et al. N Engl J Med 2011;365:981-992

Why are NOACs Better for the Brain?

Thrombin (IIa)

Intrinsic (contact) Xa

Prothrombin (II) Fibrinogen Fibrin

X Extrinsic (tissue factor)

VKA (warfarin)

II VII IX X

IX VII

Conclusions

• Paroxysmal AF is a major cause of stroke

that is under-diagnosed

• Many AF patients are not anticoagulated
• Resistance to NOACs based on reversibility

is a false argument