Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Prof. Mirza Dilić, MD, PhD, FESC, FACC

Clinical Center Sarajevo Director Internal Clinics and Departments

Stroke prevention in atrial fibrillation

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Epidemiological data

~15% of all strokes affected patients with AFib

Risk of stroke in AFib patients who do not receive OAC or ATT is ~ 5% per year

Prevalence of AFib is about 10% in patients age 80 yrs

Patients of 75 yrs with AF have risk of thromboembolism > 4%

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Atrial fibrillation is an independent risk factors for stroke.

Several factors increased the risk for stroke in elderly patients with AFib.

Non-valvular AFib is associated with an increased risk of stroke.

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Patients with AFib may present with variety of symptoms, including;

palpitations, exercise intolerance, heart failure, chest pain, sincope, dissiness, and stroke.

In the USA and Europe, about 20% of all hospital admissions have an AFib either primary or secondary diagnosis.

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Loss of atrial systolic function results in sluggish blood flow in the atrium Disturbed atrial endothelial function

and activation of coagulation factors, Cloth formation in the atrium.

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

to control ventricular rates,

to restore and maintain sinus rhythm,

to prevent thromboembolic complications

Therapy of AFib, therefore, involve measures:

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

ACC / AHA / ESC Guidelines

2001

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

ACCP Guidelines

2008

www.escardio.org/guidelines

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

CHADS2 Cardiac failure Hypertension Age, Diabetes Stroke (doubled)

CHADS2 scoring system is used as basis for risk stratification of thromboembolic events

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Recent CHF Age over 75, Hypertension, Diabetes.

Prior Stroke – 2 points

In CHADS2 - 1 point is given for followingclinical variables:

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

CHADS2 score of 0 – should not require antithrombotic therapy.

CHADS2 score of 1 – may be treated with Aspirin or Warfarin.

CHADS2 score of 2 or more - should be treated with Warfarin with a target INR of 2.0 to 3.0

www.escardio.org/guidelines

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

www.escardio.org/guidelines

www.escardio.org/guidelines

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Class I (Level of Evidence A)

Antithrombotic th. recommended in all pts with AF, except those with lone Afib, age < 65 yrs, or contraindications.

Antithrombotic agent should be chosen balansing - absolutes risk of stroke and bleeding and relative risk and benefit for given patient.

Warfarin (target INR 2.0 – 3.0) for patients with CHADS risk of 2 is recommended unless contraindicated.

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Class I (Level of Evidence A)

Patients with 1 “clinically non-major” risk factors are at intermediate risk and,

OAC therapy or, Aspirin 75-325 mg

Patients with mechanical valve prosthesis OAC therapy, maintaining INR of at least

2.5 (mitral) or 2.0 (aortal). (Level of Evidence B).

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Class IIa (Level of Evidence A,B)

Most patients with 1 “clinically relevant non-major” risk factor, should be considered for warfarin, rather than aspirin therapy. (A)

Patients with no risk factors, < 65 yrs, lone AF, none of the risk factors, no antithrombotic therapy should be considered, rather than aspirin. (B)

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Class IIa (Level of Evidence B,C)

Dual therapy with aspirin + clopidogrel in patients with contraindication to warfarin or refusal to use warfarin.(B)

In patients who are not at high risk and do not have mechanical valve prosthesis and going to procedure, interruption of OAC should be considered to up 48 hrs without bridging with heparin.(C)

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Class IIb (Level of Evidence C)

In patients who are at high risk and have mechanical valve prosthesis and going to procedure, bridging anticoagulation with LMWH or UH should be considered. (C)

If it is necessary to interrupt therapy for 1 week, in high risk patients, LMWH or UFH my be given.

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Class IIb (Level of Evidence C)

Following coronary revascularisation in patients with AF, warfarin may be interrupted, but resumed as soon as possible, with target INR. Aspirin may be given in hiatus.

For patients underwent PCI, clopidogrel 75 mg + warfain should be maintenance.

In BMS clopidogrel at least 1 month, sirolimus-eluting stents up to 3 months, and paclitaxel-eluting stent up to 6 months.

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

For cardioverson of acute episodes that are of less than 48 hours’ duration, anticoagulation is not required.

For episode that are of greater than 48 hours’ duration, or when duration is uncertain, 3 to 4 weeks of warfarin anticolgulation before cardioversion is recommended.

In patients without risk factors for stroke, anticolagulation is maintained for at least 4 weeks after conversion.

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

ACCP Guidelines

2012

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

CHEST 2012 9 ed. Executive Summary

Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Guyatt GH, MD, FCCP,  Aki EA, MD, PhD, MPH, Crowther M, MD, Gutterman DD, MD, FCCP, Schuemann HJ, MD, PhD, FCCP, and for the American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel*

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

For patients with AF, including those with paroxysmal AF, who

are at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score = 0), we suggest no therapy rather than antithrombotic therapy (Grade 2B).

For patients who do choose antithrombotic therapy, we suggest aspirin (75 mg to 325 mg once daily) rather than oral anticoagulation (Grade 2B) or combination therapy with aspirin and clopidogrel (Grade 2B).

Antithrombotic Therapy for Atrial Fibrillation Nonrheumatic Atrial Fibrillation (AF)

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

For patients with AF, including those with paroxysmal AF, who are at intermediate risk of stroke (eg, CHADS2 score = 1), we recommend oral anticoagulation rather than no therapy (Grade 1B). We suggest oral anticoagulation rather than aspirin (75 mg to 325 mg once daily) (Grade 2B) or combination therapy with aspirin and clopidogrel (Grade 2B).

For patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than concerns about major bleeding), we suggest combination therapy with aspirin and clopidogrel rather than aspirin (75 mg to 325 mg once daily) (Grade 2B).

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AF and intermediate risk of stroke

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

For patients with AF, including those with paroxysmal AF, who are at high risk of stroke (eg, CHADS2 score = 2), we recommend oral anticoagulation rather than no therapy (Grade 1A), aspirin (75 mg to 325 mg once daily) (Grade 1B), or combination therapy with aspirin and clopidogrel (Grade 1B).

For patients with AF, including those with paroxysmal AF, for recommendations in favor of oral anticoagulation we suggest dabigatran 150 mg twice daily rather than adjusted-dose VKA therapy (target INR range, 2.0-3.0) (Grade 2B).

AF and high risk of stroke

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

For patients with AF and mitral stenosis, we recommend adjusted-dose VKA therapy (target INR range, 2.0-3.0) rather than no therapy, aspirin (75 mg to 325 mg once daily), or combination therapy with aspirin and clopidogrel (all Grade 1B).

For patients with AF and mitral stenosis who are unsuitable for or choose not to take adjusted-dose VKA therapy (for reasons other than concerns about major bleeding), we recommend combination therapy with aspirin and clopidogrel rather than aspirin (75 mg to 325 mg once daily) alone (Grade 1B).

Patients With AF and Mitral Stenosis

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

In ACC /AHA / ESC guideline 75 - 325 mg/day

ACCP guideline 75 -100 mg/day

ESC/ACCP/ACC/AHAOpie et al.

Aspirin

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Aspirin + warfarinAspirin + clopidogrel + warfarinAspirin 50 mgWarfarin with target INR of 1.8 -2.0

Aspirin

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Novel antithrombotics

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

Anti-thrombin – Dabigatran 150 mg. twice daily.

By intention-to-treat, rivaroxaban was non-inferior to warfarin but did not achieve superiority.

FDA approval

Anti Xa - Rivaroxaban once daily. By intention-to-treat, rivaroxaban was non-inferior to warfarin.

FDA approval

Safety

Similar rates of bleeding and adverse events

Less CVI and fatal bleeding

Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina

The key for optimal therapy is risk stratification. Appropriate balansing between benefit and risk of bleeding.