The patient, a 73-year-old man with atrial fibrillation, hypertension, and diabetes, presented with symptoms of a transient ischemic attack (TIA). Tests ruled out bleeding and the patient was diagnosed with a TIA. He was prescribed warfarin and had his international normalized ratio monitored and maintained between 2-3 to prevent further strokes, and did not experience another TIA in the following year.

1. ANTICOAGULATION
THERAPY FOR ATRIAL
FIBRILLATION
Lyndon Woytuck
MBBS4 Programme at St George’s University of London delivered by the
University of Nicosia
Sheba Medical Center at Tel Hashomer

2. PRESENTATION TO PRIMARY CARE CLINIC
• A 73-year-old man presents with a history of atrial fibrillation (AF), hypertension, and
diabetes. His daughter, who accompanied the patient, states that yesterday the
patient had a period when he could not speak or understand words, and that
approximately 4 weeks prior he staggered against a wall and was unable to stand
unaided because of weakness in his legs. She states that both instances lasted
approximately a half-hour. She was unable to persuade her father to go to the
emergency room either time.
What is the probable diagnosis of this
episode?

3. FURTHER NOTES
• Past medical history: Hypertension for 15 years, well controlled; diabetes for the past 10 years.
• Medications: Diltiazem CD 300 mg daily; lisinopril 40 mg daily; metformin 500 mg twice daily; aspirin 81
mg daily.
• Allergies: No known drug allergies (NKDA).
• Drug history: Smoked 2 packs a day; quit when he was diagnosed with hypertension. Drinks 1 beer a
day.
• Family history: Mother deceased (age 79, stroke); father deceased (age 64, colon cancer); 1 brother (age
70, diabetes, prostate cancer); 1 sister (age 65, hyperlipidemia).
• Social history: Lives with wife, aged 69; has 2 children; worked for 40 years as a welder.
• Review of systems: Denies dyspnea, dizziness, or syncope; denies focal motor weakness or loss of
sensation, except for the reported incident.
• Physical exam: Vitals: height = 70 inches; weight = 185 pounds; body mass index = 26.5; BP = 134/82 mm
Hg; heart rate = 88 bpm at rest, irregularly irregular pattern.
Was his anticoagulant therapy
adequate?

4. ATRIAL FIBRILLATION
• What is it?
• The most common arrhythmia in adults and increasing in prevalence (lifetime risk 1 in 4)
• Chaotic and irregular atrial arrhythmia; prevalence increases progressively with age
• What does it mean for circulation?
• Significantly increased stroke risk (affect large area of brain  fatality or bedridden)
• Framingham study 17x in rheumatic AF, 5x in non
• Thromboembolic events are a large cause of morbidity and mortality
• High prevalence of left atrial appendage thrombus due to relative stasis during fibrillation
• Relative hypercoagulable state found in vitro

5. ATRIAL FIBRILLATION
• Generally >70 years with cardiac or non-cardiac problems, such as hypertension, coronary artery
disease, valvular disease, heart failure, obesity, and sleep apnoea or pulmonary disease
• Significant morbidity and mortality, including palpitations, dyspnoea, angina, dizziness or syncope,
and features of CHF, tachycardia-induced cardiomyopathy, stroke, and death. Many are
asymptomatic or have less specific symptoms, such as mild dementia or silent strokes.
• ECG: absent P waves, fibrillatory waves, and irregularly irregular QRS complexes
• Treatment depends on severity of symptoms, duration of AF, and comorbidities. Rate correction, or
rate plus rhythm, along with anticoagulation in high-risk patients.
• beta-blockers, calcium blockers, digoxin, anti-arrhythmic agents, ablation for pulmonary vein
isolation and left atrial substrate modification, pacemakers, and ablation of the atrioventricular node
• Risks and benefits of therapy need to be weighed based on multiple clinical factors to optimise
outcome.

6. DIAGNOSIS AND EARLY MANAGEMENT OF
ATRIAL FIBRILLATION
• Most patients present with chronic AF, however most with acute AF do not require
immediate intervention, but require medical therapy to control ventricular rate (Beta
blockers, calcium channel blockers, and digoxin)
• Patients who develop haemodynamic compromise should have immediate direct
current cardioversion.
• If the precise timing of the onset of AF is unclear, a transoesophageal
echocardiogram must be performed to exclude left atrial clots before cardioversion.
The tracing demonstrates the absence of P
waves (long arrow), as well as the presence of
the fine f waves of atrial fibrillation (short
arrows). Note the irregularity of the
ventricular response, as seen from the
variable R-R interval (brackets).

7. ANTICOAGULATION
• The preventative benefit in AF is for reduction of embolization leading to stroke
• Indicated for moderate to severe risk group where benefit > risks of bleeding
• Anticoagulation is universally recommended for patients with valvular atrial
fibrillation or those with mechanical heart valves (without contraindication)
• Oral Coumadin (Warfarin) or NOACs (direct thrombin inhibitors and factor Xa
inhibitors) have shown superior efficacy and safety in RCTs (non-valvular AF)
• In low-risk patients, or in patients with contraindications to oral anticoagulation,
aspirin 81–325 mg daily is recommended as an alternative

8. RISK STRATIFICATION
• Stroke risk estimation in non-valvular AF:
• CHADS2
• 1 - congestive heart failure; 1 – hypertension; 1 - age
>75 years; 1 - diabetes mellitus; 2 - history of stroke or
transient ischemic attack
• CHA2DS2-VASc score further stratifies
• 1 for age 65-74 years,
• 2 points for age ≥75 years
• 1 for female sex
• 1 for presence of vascular disease (coronary,
peripheral, or aortic plaque on imaging)
• 1 CHADS factor classifies moderate risk
• Highest risk: prior thromboembolism (stroke,TIA, or
systemic embolism) and rheumatic mitral stenosis
• Bleeding Risk: ATRIA (Anemia (3), Severe renal disease
(3), Age ≥75 (2), Previous bleeding (1), Hypertension
(1)),
HAS-BLED (Hypertension (1), Abnormal liver or renal
function (1x), Stroke (1), Bleeding (1), Labile INR (1), >65
years (1), Drugs or alcohol (1x)), and HEMORR2HAGES
scores
• In practice these parameters are hardly used, no
benefit has been shown for withholding anticoagulation
on high bleeding score
• Guidelines cite bleeding scores should reduce
subjectivity in decision, but emphasize these scores
should not solely exclude treatment
• Current evidence suggests net clinical benefit for all
except those with the highest risk of bleeding

9. • Event rates, according to scores on the
various risk stratification algorithms, for
(A) stroke and (B) bleeding
• BMJ 2014;348:g2116

10. ANTICOAGULATION
• Vit K antagonist Warfarin 64% (95%CI 49-74%) RR reduction for stroke VS placebo
39% (22% to 52%) RR reduction VS antiplatelet drugs
• Intracranial haemorrhage risk with Warfarin, GI bleed risk with direct thrombin
inhibitor Dabigatran (lower overall bleed risk) and Xa inhibitors Rivaroxaban &
Apixaban
• Novel anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) are
collectively safer (avoiding intracerebral hemorrhage) and more effective than
warfarin
• NOACs have much shorter time to onset and offset and each exhibits some level of renal
clearance
• No easy monitoring using readily available commercial assays for anticoagulation

11. MONITORING ANTICOAGULATION
• Adherence is a major problem esp.Warfarin: + drug-drug, drug-food interactions
• Bridging required in high risk patients, but can be stopped otherwise <5 day periods
• Recommended in a dose adjusted to achieve the target intensity international
normalized ratio (INR) of 2.0 to 3.0
• Regular monitoring by phlebotomy is required in warfarin therapy
• NOACs do not require monitoring and interact less, but specific assays are not widely
available so adherence subjective
• PT and PTT can be evaluated, but are not drug or dose specific

12. BLEEDING EVENTS
• Reversal of Coumadin effects by blood products (acutely and temporarily) or
replacing vitamin K (gradually and permanently)
• NOACs have no effective reversal strategy, but recombinant hemostatic factor
concentrates and developmental small molecules have been tried (no increased
mortality or morbidity compared to warfarin related events)
• Plasma not useful w/out primary coagulopathy; factor concentrates have thrombotic risk
• Supportive care (including volume resuscitation, hemodynamic support, and primary
intervention)

13. CASE CONTINUED
• You order a CT scan, complete blood count with platelet count, prothrombin time
(PT), activated partial thromboplastin time (aPTT), blood urea nitrogen (BUN),
creatinine, glucose level, and erythrocyte sedimentation rate (ESR). Results indicate
no hemorrhaging, and you make a diagnosis of a TIA.
• You prescribe warfarin for the patient and titrate to INR 2.5.With continued
monitoring to maintain the therapeutic range, the patient does not experience a
stroke or TIA in the following year.
What therapy should be prescribed?

14. REFERENCES
• Anticoagulation in atrial fibrillation BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g2116 (Published 14 April 2014)
BMJ 2014;348:g2116 Accessed from:
http://www.bmj.com/content/348/bmj.g2116?hwshib2=authn%3A1457547541%3A20160308%253Aa462ca89-531f-418c-
8315-688b98a76a72%3A0%3A0%3A0%3AXQvXtuVMTQWnOc9RYC5q5Q%3D%3D
• Acute Atrial Fibrillation. Chronic Atrial Fibrillation. Accessed from: http://bestpractice.bmj.com/best-
practice/monograph/3.html
• Case Study 2: Patient With Atrial Fibrillation and Prior Transient Ischemic Attack (TIA): Anticoagulant Therapy,
Uncontrolled Hypertension,Dyslipidemia Robert J. Adams, MD, Chair; Jan N. Basile, MD; Philip B. Gorelick, MD. CME
Released: 07/27/2011;Valid for credit through 07/27/2012 Accessed from: http://www.medscape.org/viewarticle/744735
• Acute Management of Atrial Fibrillation: Part I. Rate and Rhythm Control. DANA E. KING, M.D., LORI M. DICKERSON,
PHARM.D., and JONATHAN L. SACK, M.D. Medical University of South Carolina, Charleston,South Carolina. Am Fam
Physician. 2002 Jul 15;66(2):249-257. Accessed from: http://www.aafp.org/afp/2002/0715/p249.html