Non-valvular atrial fibrillation (NVAF) should be treated with direct-acting oral anticoagulants (DOAC) based on stroke risk (a CHADS2 ≥ 1) and corrected for risk of bleeding (HAS-BLED).
Atrial Fibrillation is associated with thromboembolism, heart failure, and death. Fifteen percent (15%) of strokes are caused by an embolus arising from the left atrium, a pathological manifestation well recognised in a heart whose atria fibrillate.
Haemodynamic stability and anticoagulation are the main considerations in a person presenting with atrial fibrillation. Either of rate or rhythm control can often be achieved in the emergency setting and the patient discharged home on oral anticoagulation to return at a later date for formal workup.
Stabilising the patient with atrial fibrillation in the acute setting:
Stroke Risk in General: According to the CDC, 795,000 people had a stroke in the United States during 2010. Of these, 691,650 (87%) were ischemic strokes. This gives an incidence (based on a 2010 population of 309 million) of ischaemic stroke in the United States of 223 per 100,000 people per year.
Use the SPARC (Stroke Prevention in Atrial Fibrillation Risk) tool for estimating risk of stroke and benefits & risks of antithrombotic therapy in patients with chronic atrial fibrillation: http://www.sparctool.com/ (Mobil version: http://www.sparctool.com/mobile/#home).
The risk is lower in European countries than in the Framingham cohort. In the UK General Practice Research Database (UKGPD), the incidence was 115-150 per 100,000 people per year. In 2006, Scotland had a stroke incidence of 166 per 100,000 people (85% ischaemic, 25% cardioembolic).
Stroke Risk by Ethnicity — Northern Manhattan Stroke Study: The average annual age-adjusted incidence rate for all stroke was: 223 per 100 000 blacks; 196 per 100,000 Hispanics; 93 per 100 000 whites. Cerebral infarction (ischaemic stroke) accounts for 77%, so that the average annual age-adjusted incidence rate for ischaemic stroke was:
- Blacks: 172 per 100,000
- Hispanics: 151 per 100,000
- Whites: 72 per 100,000
∴ Ischaemic stroke incidence is 70 per 100,000—double that for Hispanics, and 2.5 times for Blacks.
Stroke Risk in DM — Greater Cincinnati / Northern Kentucky Stroke Study
- 45-54 year old whites: 5.3 x
- 35-44 year old blacks: 9.9 x
∴ Diabetes increases the risk of stroke, and at an earlier age.
Framingham 10-Year, Stroke Risk-Factors:
- age
- systolic BP
- treatment for HTN
- diabetes mellitus: 2 x
- cigarette smoking
- h/o CVD (cardiovascular disease)
- h/o AF (atrial fibrillation): 5 x
- LVH (left ventricular hypertrophy)
Other independent risk factors:
-
- recent cardiac failure or moderately impaired LVEF: 1.4 x
- prior TIA / Stroke: 1.9 x
That is the general idea of the numbers involved. Now let us look at patients with atrial fibrillation.
Stroke Risk with Atrial Fibrillation
Five percent (5%) of those over 65 years-old have Atrial Fibrillation, conferring a 4–5 times greater risk of stroke than that of the general population (between 2–7 x depending on additional risk factors). And when they do have a stroke, it’s generally more severe, with more frequent recurrences, and associated with greater mortality (nearly twice as likely to be fatal) than strokes in patients without atrial fibrillation.
Stroke risk is generally age-dependent, a higher risk with advancing age. While stroke risk with atrial fibrillation is also age-dependent (see Framingham Heart Study), it is relatively high (4 x) in the 50-59 year age group, presumably reflecting greater underlying pathology in those with a younger-onset arrhythmia. Otherwise, in patients with AF, age raises the relative risk of stroke or systemic embolism by a factor of about 1.4 with each advancing decade:
- 50-59 years: 4 x (1.5%)
- 60-69 years: 2.6 x
- 70-79 years 3.3 x
- 80-89 years: 4.5 x (23.5%)
In those with atrial fibrillation, the younger age group of 50-59 years has a relatively high risk of stroke because of underlying pathology. Stroke risk increases by a factor of 1.4 for each decade thereafter such that the risk of a stroke in the coming year for an octogenarian with atrial fibrillation is 23.5%.
What do you to tell the patient?
You need to be familiar with the baseline risk for the person in front of you—i.e. age, race, nationality. Multiply this background rate by the relative risk to give an approximate of their risk of stroke.
For example: the approximate stroke risk for a 65-year old with atrial fibrillation will be the background risk multiplied by 2.6 (above).
Scoring systems devised to help estimate stroke risk in patients with atrial fibrillation help guide recommendation for antithrombotic therapy. CHADS-VASC has proven the most reliable of these. The threshold for anticoagulant treatment is considered to be a CHADS-VASC of 2 or more.
If there are no CHADS-VASC risk factors (score of 0), anticoagulation is not necessary. A person with a CHADS-VASC of 1 may either be treated with Aspirin (ASA) or oral anticoagulation (OAC).
Anticoagulation
Recall the coagulation cascade:
Systemic Embolisation (e.g. Ischaemic Stroke) Rate with NOACs
- Dabigatran (Pradaxa):
- 110 mg bd: 1.54
- 150 mg bd: 1.12
- Rivaroxaban (Xarelto): 1.7
- Apixaban (Eliquis): 1.27
- Edoxaban (Savaysa, Lixiana):
- 30 mg od: 1.61
- 60 mg od: 1.18
- Warfarin (Coumadin, Marevan): 1.50 – 2.2
The risk of bleeding from OACs also varies with age:
- younger patients: 4.7% per year
- ≥80 years old: 13.1% per year
Bleeding Rate with NOACs
- Dabigatran (Pradaxa) % per year
- Major: 2.9 – 3.4% per year
- Intracranial: 0.2 – 0.3% per year
- GIT: 1.1 – 1.5% per year
- Rivaroxaban (Xarelto)
- Major: 3.6 per 100 patient-years
- Intracranial: 0.5 per 100 patient-years
- GIT: 3.2 per 100 patient-years
- Apixaban (Eliquis)
- Major: 2.13% per year
- Intracranial: 0.33% per year
- GIT: 0.76% per year
- Edoxaban (Savaysa, Lixiana)
- Major: 1.61% per year
- Intracranial: 0.26% per year
- GIT: 0.82% per year
- Warfarin (Coumadin, Marevan)
- Major: 3.1 – 3.6% per year
- Intracranial: 0.7 – 0.85% per year
- GIT: 0.86 – 2.2% per year
Warfarin’s “ethical metrics”:
- NNT: 25 to prevent 1 ischaemic stroke
- NNH: 384 to cause 1 intracranial haemorrhage
- NNT: 42 to prevent 1 death
- NNH: 25 to cause 1 bleed
If you prescribe warfarin for 2,000 people with atrial fibrillation, you will prevent 48 deaths and 80 thromboembolic strokes but cause 80 general bleeds and just over 5 intracranial haemorrhages.
HAS-BLED Score and Annual Bleeding Risk
A score of 2-3 is a moderate bleeding risk:
- A score of 0-1 has about a 1% annual risk of bleeding
- A score of 2 has almost 2% (1.9%) risk of annual bleeding
- A score of 3 has 3.74% annual risk of bleeding
- A score of 4 has an 8.7% annual risk of bleeding
- A score of 5 has a 12.5% annual risk of bleeding
Other factors impacting upon shared decision making include renal function, because all the NOACs are, at least partially, renally excreted. Dabigatran is the most renally-excreted NOAC. Otherwise, the NOACs have safety data in people with a CrCl < 30 mL/min. (Likewise, there are no good data for warfarin in people with a CrCl < 30.)
- CrCl 30–50: consider dose reduction
- CrCl < 30: reduce dose
- CrCl < 15: epixaban preferred
Monitor renal patients closely. As a rule of thumb:
- If CrCl is 30 (mL/min), review the person every 3 months.
- If CrCl is 60 (mL/min), review the person every 6 months.
(All other things being equal then, a cheeky rule of thumb for follow-up in months is given by dividing the CrCl by 10.)
NOACs before Surgery
Hold rivaroxaban and apixaban for 2 days. Use CrCl guidance for dabigatran.
Restarting NOACs
After procedures with complete haemostasis, you can safely restart a NOAC in 8 hours. For VTE prophylaxis postoperatively, start the NOAC 8 hours postoperatively. For treatment of AF, restart the NOAC on the third postoperative day (Day 3).
Transitioning back to VKA (e.g. worsening renal function)
It may take 5-10 days to achieve therapeutic INR. It is wise to also check the INR 24 hours after the last DOAC dose.
The DOACs
- 2018 Guidelines for the Diagnosis and Management of Atrial Fibrillation in Australia: key points for GPs
Annotations
- NOAC/DOAC = novel or direct-acting oral anticoagulant
- The risk of stroke in those with valvular AF (not considered in this summary) is up to 17 x that of the general population.
- Annual stroke risk: 3.2% (on Aspirin), whether paroxysmal or permanent AF
Further Reading
- Blood & Clots Series: How do you stop warfarin for surgery?, Canadiem
- Atrial Fibrillation — EM (Emergency Medicine) Cases, Episode #20
- Oral anticoagulants in non-valvular atrial fibrillation for primary stroke prevention (no prior stroke) – the NNT
- Weighing up the benefits and risks of therapy – Thrombosis Adviser
- SPARC – Stroke Prevention in Atrial Fibrillation Risk Tool, Peter Loewen
- Peterson E, Kakkar A. Assessing the Risk for Stroke in Patients with Atrial Fibrillation. Medscape Education
- Di Nisio M, Middeldorp S, Büller HR. Direct Thrombin Inhibitors. N Engl J Med 2005;353:1028-40.
References
- Seshadri S, Beiser A, Kelly-Hayes M, Kase C, Au R, Kannel W, Wolf. The Lifetime Risk of Stroke: Estimates From the Framingham Study. Stroke. 2006;37:2 279–280
- Jauch E, Lutsep H. Ischemic Stroke. Medscape Practice Essentials
- Sacco RL, Bernadette Boden-Albala B, Gan R, Chen X, Kargman DE, Shea S, Paik MC, Hauser WA. Stroke Incidence among White, Black, and Hispanic Residents of an Urban Community: The Northern Manhattan Stroke Study. Am. J. Epidemiol. (1998) 147 (3): 259-268.
- Lee S, Shafe A, Cowie M. UK stroke incidence, mortality and cardiovascular risk management 1999–2008: time-trend analysis from the General Practice Research Database. BMJ Open, 2011
- Peterson E, Kakkar A. Assessing the Risk for Stroke in Patients with Atrial Fibrillation. Medscape Education
- Dobesh P, Fanikos J. Review Article. Direct Oral Anticoagulants for the Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation: Understanding Differences and Similarities. Drugs (2015) 75:1627–1644
- Medi C, Hankey G, Freedman S. Stroke Risk and Antithrombotic Strategies in Atrial Fibrillation. Stroke. 2010;41:2705-2713
- Camm J, Kirchhof P, Lip G. Guidelines for the management of atrial fibrillation. The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). European Heart Journal (2010) 31, 2369–2429
- Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD001927. Review. PubMed PMID: 16034869.
- Atrial fibrillation is a major risk factor for stroke – Thrombosis Adviser
- Jorgensen HS, Nakayama H, Reith J et al. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke 1996;27:1765–1769.
- Epidemiology of Ischemic Stroke in Patients With Diabetes: The Greater Cincinnati/Northern Kentucky Stroke Study
- Expert Roundtable: Challenging Cases in Stroke Prevention for AF. Peer Voice Internal Medicine podcast. November 14, 2015.
- Guimarães PO, Kaatz S, Lopes RD. Practical and clinical considerations in assessing patients with atrial fibrillation for switching to non-vitamin K antagonist oral anticoagulants in primary care. IntJGenMed. Volume 2015:8 Pages 283—291
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