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Table 2 Guidelines for the management of stroke in NVAF

From: A case-based approach to implementing guidelines for stroke prevention in patients with atrial fibrillation: balancing the risks and benefits

 

2012 AHA/ASA: Scientific Advisory [8]

2012 ACCP [11]

2012 ESC [7]

2014 AAN [9]a

2014 ACC/AHA/HRS [10]

Stroke risk

Guideline recommendations by stroke risk

Low

CHADS2 = 0

CHADS2 = 0

CHA2DS2-VASc = 0

Clinicians might not offer anticoagulation to patients with NVAF who lack additional risk factors

CHA2DS2-VASc = 0

Aspirin, based on patient preference, estimated bleeding risk if anticoagulated, and access to high-quality anticoagulation monitoring

No therapy suggested rather than antithrombotic therapy

No antithrombotic therapy recommended

Clinicians might offer antithrombotic therapy with aspirin or no therapy at all

Reasonable to omit antithrombotic therapy

 

If antithrombotic therapy chosen, aspirin (75–325 mg/d) suggested rather than OAC or aspirin plus clopidogrelb

   

Moderate

CHADS2 = 1

CHADS2 = 1

CHA2DS2-VASc = 1

Not discussed

CHA2DS2-VASc = 1

 

Aspirin, based on patient preference, estimated bleeding risk if anticoagulated, and access to high-quality anticoagulation monitoring or adjusted-dose warfarin in appropriate patients

OAC suggested rather than no therapy. OAC suggested rather than aspirin alone or aspirin plus clopidogrel.b If OAC unsuitable or not desired, aspirin plus clopidogrelb suggested rather than aspirin alone

OAC therapy with adjusted-dose VKA (INR 2.0–3.0); a direct thrombin inhibitor (dabigatran); an oral factor Xa inhibitor (e.g., rivaroxaban, apixaban) should be considered, based upon an assessment of the risk of bleeding complications and patient preferences. For female patients aged <65 years with lone AF (CHA2DS2-VASc = 1 due to sex), no antithrombotic therapy should be considered

 

No therapy or OAC or aspirin may be considered

High

CHADS2≥2

CHADS2≥2

CHA2DS2-VASc ≥2

 

CHA2DS2-VASc ≥2

 

Adjusted-dose warfarin in appropriate patients (in patients unsuitable for warfarin, aspirin plus clopidogrelb offers more protection against stroke than aspirin but with an increased risk of major bleeding)

OAC suggested rather than no therapy, aspirin alone, or aspirin plus clopidogrel.b If OAC unsuitable or not desired, aspirin plus clopidogrelb suggested rather than aspirin alone

OAC therapy with adjusted-dose VKA (INR 2.0–3.0); a direct thrombin inhibitor (dabigatran); an oral factor Xa inhibitor (e.g., rivaroxaban, apixaban) recommended, unless contraindicated

Clinicians should routinely offer anticoagulation to patients with NVAF and a history of TIA or stroke

OAC recommended (warfarin, dabigatran, rivaroxaban, or apixaban)

Treatment options

Guideline recommendations by agent

Adjusted-dose VKA

See recommendations by CHADS2 score

Patients with AF and mitral stenosis

 

INR of 2.0–3.0 likely reduces frequency and severity of ischemic stroke vs lower INR levels

Patients with mechanical heart valve (target INR 2.0–3.0 or 2.5–3.5 based on type and location of prosthesis)

 

Patients with AF and stable CAD

  

Patients with NVAF and CHAD2DS2-VASc ≥2 with end-stage CKD (CrCl <15 mL/min) or on hemodialysis

 

Patients with AF and ACS not undergoing stent placement (in combination with single antiplatelet for first 1–12 mo, after which treat as for patients with AF and stable CAD)

   

Dabigatran

150 mg bid is an efficacious alternative to warfarin in patients with NVAF who have ≥1 additional risk factor for stroke and CrCl >30 mL/min

 

Recommended over adjusted-dose VKA in cases where OAC recommended

Probably more effective than warfarin for reducing risk of stroke or SE

Recommended for patients unable to maintain a therapeutic INR level with warfarin

Reduce dosage to 75 mg bid in patients with moderate renal impairment (CrCl 15–30 mL/min)c

 

Dabigatran 150 mg bid recommended for most patients

Hemorrhage risk was similar overall between dabigatran 150 mg and warfarin; ICH was less frequent with dabigatran 150 mg than warfarin; GI bleeding more frequent with dabigatran 150 mg than with warfarin

May be considered in patients with renal impairment: 150 mg bid in patients with mild renal impairment (CrCl >30 mL/min); 150 mg or 75 mg bid in patients with moderate renal impairment (CrCl >30 mL/min); 75 mg bid in patients with severe renal impairment (CrCl 15–30 mL/min)

• Dabigatran 110 mg bid recommended for:

• Elderly patients (aged ≥80 y)

• Concomitant use of interacting drugs

• HAS-BLED ≥3

• Moderate renal impairment (CrCl 30–49 mL/min)

Not recommended in patients with severe renal impairment (CrCl <15 mL/min)

Recommended over adjusted-dose VKA in cases where OAC recommended

Not recommended in patients with severe renal impairment (CrCl <30 mL/min)

 

Not recommended for patients with CrCl<15 mL/min

Rivaroxaband

20 mg/d is a reasonable alternative to warfarin in patients with NVAF at moderate to high risk of stroke (prior history of TIA, stroke, or SE, or ≥2 additional risk factors) 15 mg/d may be considered in patients with renal impairment (CrCl 15–50 mL/min)c

 

Recommended over adjusted-dose VKA in cases where OAC recommended

In patients with NVAF at high risk of cerebral or systemic embolism. Probably as effective as warfarin for prevention of cerebral and systemic embolism, with no difference in risk of major bleeding episodes except GI bleeding

Recommended for patients unable to maintain a therapeutic INR level with warfarin

May be considered in patients with renal impairment: 20 mg/d for patients with mild renal impairment (CrCl >50 mL/min); 15 mg/d for patients with moderate or severe renal impairment (CrCl 15–50 mL/min)

Rivaroxaban 20 mg/d recommended for most patients

Rivaroxaban 15 mg/d recommended for:

• HAS-BLED ≥3

• Moderate renal impairment (CrCl 30–49 mL/min)

Should not be used in patients with severe renal impairment (CrCl <15 mL/min)

Not approved at time of guideline preparation

Not recommended in patients with severe renal impairment (CrCl <30 mL/min)

Associated with lesser frequency of ICH and fatal bleeding compared with warfarin

Not recommended for patients with CrCl < 15 mL/min

Apixabane

As an alternative to warfarin or aspirin: 5 mg bid is relatively safe and efficacious in patients with NVAF who have ≥1 additional risk factor and ≤1 of the following additional criteria: age ≥80 y, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL

 

Recommended over adjusted-dose VKA in cases where OAC recommended apixaban 5 mg bid

In patients with NVAF at moderate risk of embolism, 5 mg bid is likely more effective than warfarin

Recommended for patients unable to maintain a therapeutic INR level with warfarin

• 2.5 mg bid may be considered in patients with ≥2 of the additional criteria described abovec

Apixaban 2.5 mg bid recommended for patients with renal impairment

Superiority is related to decreased risk of bleeding and reduced mortality, while its effect on reduction in risk of cerebral and systemic embolism is not superior to warfarin

5.0 mg bid in patients with mild or moderate renal impairment or 2.5 mg bid in patients who meet dose reduction criteria (CrCl ≥1.5 mg/dL, ≥80 years of age, body weight ≤60 kg)

Should not be used in patients with severe renal impairment (CrCl <25 mL/min)

Not approved at time of guideline preparation

Not recommended in patients with severe renal impairment (CrCl <30 mL/min)

Likely more effective than aspirin for decreasing risk of stroke or SE in patients with NVAF who have moderate risk of embolism and are not candidates for warfarin

No recommendation in patients with severe renal impairment or end-stage CKD

Edoxaban

Not approved at time of guideline preparation

Not approved at time of guideline preparation

Not approved at time of guideline preparation

Not approved at time of guideline preparation

Not approved at time of guideline preparation

Other agents

   

Oral anticoagulation is likely more effective than clopidogrel plus aspirin, but ICH is more common

 

Triflusal plus acenocoumarol and moderate-intensity anticoagulation (INR 1.25–2.0) is likely more effective than treatment with acenocoumarol alone and conventional-intensity anticoagulation

Combination of low-dose aspirin and dose-adjusted VKA therapy probably increases risk of hemorrhage

Combination of clopidogrel and aspirin reduces risk of major vascular events but increases risk of major hemorrhage compared with aspirin alone

  1. AAN American Academy of Neurology, ACC American College of Cardiology, ACCP American College of Chest Physicians, ACS acute coronary syndrome, AF atrial fibrillation, AHA American Heart Association, ASA American Stroke Association, bid twice daily, CAD coronary artery disease, CHADS 2 Congestive heart failure, Hypertension, Age ≥65 y, Diabetes, Stroke or transient ischemic attack (doubled), CHA 2 DS 2 -VASc Congestive heart failure, Hypertension, Age ≥75 y (doubled), Diabetes, Stroke or transient ischemic attack (doubled), Vascular disease, Age 65–74 y, Sex category (female), CKD chronic kidney disease, CrCl creatinine clearance, ESC European Society of Cardiology, GI gastrointestinal, HAS-BLED Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly, HRS Heart Rhythm Society, ICH intracranial hemorrhage, INR international normalized ratio, NVAF nonvalvular atrial fibrillation, OAC oral anticoagulant, SE systemic embolism, TIA transient ischemic attack, VKA vitamin K antagonist
  2. aAAN recommends that clinicians use risk stratification tools to help determine stroke risk in patients with NVAF, but cautions physicians not to rigidly interpret anticoagulation thresholds suggested by these tools and does not stratify recommendations using a scoring system
  3. bIn the United States, clopidogrel and the more recently developed antiplatelet agents, prasugrel and ticagrelor, are used in patients with ACS, but none are indicated for stroke prevention in AF
  4. cRecommendations made; however, safety and efficacy have not been established
  5. dRivaroxaban should be administered once daily with the evening meal
  6. e2.5 mg bid if any 2 patient characteristics present: CrCl ≥1.5 mg/dL, ≥80 years of age, body weight ≤60 kg