Atrial Fibrillation & Anticoagulation

How to read this summary

• Canadian sources come first, US sources second. Each point has a source tag like ^[S1] or ^[U1]. The full list of tags is at the end.
• "WARNING" marks a conflict or an old document. "Unconfirmed" means it could not be verified in the sources used. Never trust an unconfirmed item without checking.
• PEBC follows Canada. When Canada and the US differ, the Canadian answer is the exam answer.
• IMPORTANT (newest guideline): the newest Canadian AF guideline found is the 2020 CCS/CHRS Comprehensive Guidelines for the Management of Atrial Fibrillation (Can J Cardiol 2020;36:1847-1948). No focused update after it was found. This summary reads it through the CCS 2021 AF pocket guide ^[S1] (a summary of the 2020 guideline) and through the Thrombosis Canada guides ^[S2-S12], which are updated often (versions dated 2024 to 2026). The full 2020 guideline text was not opened. The 2023 ACC/AHA/ACCP/HRS guideline is shown only as a labelled US extra ^[U1].
• Page numbers: S1 uses the printed pocket-guide page number (PDF page = printed page + 3). Thrombosis Canada guides use "p x" = page x of the guide. Drug labels use the monograph page or section.
• Doses and numbers are for exam study, not for real patients.

1. What is atrial fibrillation (AF) and why does it matter? (the wobbling top of the heart)

• AF is a fast, irregular heartbeat that starts in the two upper chambers (the atria). It is the most common abnormal heart rhythm, and it becomes more common with age: about 10-15% of people aged 80 or older have it ^{[S2 p1]}.
• Daily-life picture: think of a washing machine that spins unevenly with the clothes bunched up. Blood in the top of the heart does not empty well, it pools, and a clump (clot) can form.
• The big danger is stroke. A clot from the left atrium travels to the brain (ischemic stroke), or to a limb or another organ. AF raises the risk of stroke or other systemic embolism about 3 to 6 times. Strokes with AF are larger and more often deadly or disabling ^{[S2 p1]}.
• That is why stroke prevention is a core part of AF treatment ^{[S2 p1]}. The six goals of AF care in the CCS pocket guide: prevent stroke, improve survival, cut heart and blood vessel risk, improve symptoms and quality of life, reduce hospital use, and prevent complications such as heart muscle weakness and falls ^{[S1 p10]}.
• Blood thinners (anticoagulants) cut stroke risk a lot. Antiplatelet drugs (such as aspirin) help much less ^{[S2 p1]}.

1.1 Types of AF (CCS definitions) ^{[S1 p2]}

• Non-valvular AF (NVAF) = AF without those valve problems. Most drug rules below are for NVAF ^{[S1 p2; S2 p1]}.
• Memory trick: "Paroxysmal = Passes in a week. Persistent = Past a week. Permanent = Parked for good."

1.2 Work-up and triggers

• Basic tests for every patient: 12-lead ECG (electrocardiogram), echocardiogram, and blood tests: complete blood count, coagulation profile, electrolytes including calcium and magnesium, kidney function, liver function, thyroid function, fasting lipids, fasting glucose and HbA1c (Hemoglobin A1c) ^{[S1 p4]}.
• Look for triggers and reversible causes: alcohol, stimulants, lack of sleep, stress, surgery, acute infection, heart or lung illness, thyrotoxicosis (overactive thyroid), and drugs such as ibrutinib ^{[S1 p3]}.
• Established AF risk factors: older age, male sex, high blood pressure, heart failure with reduced ejection fraction, valve disease, overt thyroid disease, obstructive sleep apnea, obesity, heavy alcohol use ^{[S1 p5]}.
• Pocket guide targets for risk-factor control ^{[S1 p7]}:

• Screening: CCS recommends opportunistic AF screening (for example a pulse check) in people 65 or older at routine medical visits (strong recommendation, low-quality evidence). If AF is suspected but not recorded, confirm with an ECG-type test ^{[S1 p8-9]}.
• Subclinical AF (short episodes picked up by a device): CCS suggests it is reasonable to give an oral anticoagulant (OAC) when the person is 65 or older, or has a CHADS2 score of 1 or more, and episodes last more than 24 continuous hours (weak recommendation) ^{[S1 p9]}. For episodes of 6 minutes to 24 hours and a CHA2DS2-VASc score of 3 or more, apixaban lowered stroke or systemic embolism compared with aspirin (hazard ratio 0.63) but raised major bleeding (hazard ratio 1.80). Thrombosis Canada says to decide together with the patient ^{[S6 p4; S2 p6]}.

Must remember for the exam: AF = fast irregular rhythm from the upper chambers. Main danger = stroke (3-6 times higher risk). Valvular AF = mechanical valve or moderate-severe mitral stenosis.

2. Stroke risk and bleeding risk

2.1 CHADS2 and the Canadian "CHADS-65" shortcut

• CHADS2 points: recent Congestive heart failure 1, history of Hypertension 1, Age 75 or older 1, Diabetes 1, prior Stroke or TIA (transient ischemic attack) 2 ^{[S2 p2]}.
• Canada uses the CHADS-65 algorithm to decide who needs an anticoagulant ^{[S1 p19; S2 p4-5]}: 1. Age 65 or older: give an OAC. 2. Younger than 65 but with any CHADS2 risk factor (prior stroke/TIA/embolism, high blood pressure, heart failure, diabetes): give an OAC. 3. Younger than 65, no CHADS2 factor, but with coronary or other arterial vascular disease (coronary, aortic, peripheral): an antiplatelet drug, usually aspirin (ASA, acetylsalicylic acid) 81 mg daily alone, not an anticoagulant. The CCS pocket guide also lists other antiplatelet options (clopidogrel 75 mg alone, or ASA with clopidogrel, ticagrelor 60 mg twice daily or rivaroxaban 2.5 mg twice daily) depending on the clinical situation ^{[S1 p19]}. 4. Younger than 65, no CHADS2 factor, no vascular disease: no antithrombotic drug.
• A DOAC (direct oral anticoagulant) is preferred over warfarin for NVAF ^{[S1 p19, p20]}.
• Daily-life example: a 68-year-old with no other illness already needs an anticoagulant by CHADS-65 because age 65 or more counts by itself. A healthy 52-year-old with a first AF episode and no other problem needs no blood thinner.
• When a patient cannot or will not take an OAC, aspirin 81 mg daily is suggested, but it protects much less and still raises bleeding ^{[S2 p4]}. Thrombosis Canada also notes low-dose aspirin 80-100 mg a day may be considered for low-risk patients who decline an OAC ^{[S2 p4]}.
• CHA2DS2-VASc is a longer version of CHADS2: age 65-74 scores 1 point, age 75 or older scores 2 points (instead of 1), and female sex (1 point) and vascular disease (1 point) are added. A score of 1 or more means the stroke risk without a blood thinner is usually higher than the bleeding risk ^{[S2 p1]}. Canada's recommendations are built on CHADS-65 ^{[S2 p2]}.
• The CHADS-65 figure is the CCS 2016 algorithm, reproduced in the Thrombosis Canada guide ^{[S2 p4-5]} and kept in the 2020/2021 CCS material ^{[S1 p19]}.
• Memory trick for CHADS2: "CHADS" = Congestive heart failure, Hypertension, Age 75+, Diabetes, Stroke (the S counts double).

2.2 Bleeding risk (do not use it to say no)

• Check bleeding risk in everyone, but bleeding risk alone rarely rules out an anticoagulant. People at high bleeding risk are often the ones who gain most from stopping strokes ^{[S2 p2]}.
• Fix what can be fixed: control blood pressure, cut NSAID and alcohol use, stop antiplatelet drugs that are not needed, review drugs that change blood-thinner levels, check fall risk ^{[S2 p2]}.
• HAS-BLED is a score that finds fixable bleeding risks (it is a tool for fixing risks, not a reason to deny therapy) ^{[S2 p2]}.
• Bleeding risk factors with antithrombotics (CCS): age over 65, weight under 60 kg, high blood pressure, past bleeding, heavy alcohol, labile INR (time in range below 60%), antiplatelets, NSAIDs, prednisone, anemia (hemoglobin below 110 g/L), abnormal liver tests, kidney disease ^{[S1 p27]}.
• US extra: the 2023 ACC/AHA/ACCP/HRS guideline accepts CHA2DS2-VASc and other scores; therapy is advised when the estimated stroke risk is about 2% a year or more. Bleeding scores should not be used on their own to deny anticoagulation ^[U1].

Must remember for the exam: CHADS-65 = age 65+ or any CHADS2 factor means OAC (DOAC preferred). Under 65 with only vascular disease = aspirin 81 mg. Under 65, nothing else = no drug.

3. Rate control or rhythm control?

• Two ways to treat symptoms: rate control (slow the beat, AF stays) and rhythm control (try to get back to normal rhythm). Stroke prevention is needed in either case and does not depend on whether the heart rate or rhythm looks normal ^{[S1 p10-11]}.
• Rhythm control is preferred when: AF was found within the last year, symptoms are strong or quality of life is poor, there are many recurrences, rate control is hard, or AF has weakened the heart muscle (arrhythmia-induced cardiomyopathy) ^{[S1 p11]}.
• Daily-life example: rate control is like slowing a galloping horse to a trot. Rhythm control is like trying to get the horse back in step with the band.

3.1 Long-term rate control (first-line drugs) ^{[S1 p12-13]}

• When to change the plan: if resting heart rate stays above 100 beats a minute or symptoms continue, adjust. If still not controlled, consider rhythm control or a pacemaker with AV junction ablation ^{[S1 p12]}.
• Typical oral doses: bisoprolol 2.5 mg daily up to 10 mg daily; metoprolol 12.5-25 mg twice daily up to 100-200 mg twice daily; atenolol 25 mg daily up to 100 mg daily; carvedilol 6.25 mg twice daily up to 25 mg twice daily; diltiazem extended-release 120 mg daily up to 360 mg daily; verapamil sustained-release 120-240 mg daily up to 360 mg daily; digoxin 0.125 mg daily up to 0.125-0.25 mg daily (loading not usually needed as an outpatient) ^{[S1 p13]}.
• Safety notes ^{[S1 p13]}:
• Beta-blockers: slow heartbeat, low blood pressure, tiredness, low mood. Avoid with pre-excitation or bronchospasm. Once-daily drugs (for example bisoprolol) help adherence.
• Diltiazem and verapamil: slow heartbeat, low blood pressure, swelling (diltiazem), constipation (verapamil). Not for pre-excitation, heart failure or poor LV function.
• Digoxin: nausea and vomiting, blurred vision, proarrhythmia. Rarely used alone. Careful in older women, kidney disease and with potassium-losing diuretics (for example furosemide, hydrochlorothiazide).
• Amiodarone is rarely used just for rate control because of its side-effects ^{[S1 p13]}.

3.2 Long-term rhythm control drugs (antiarrhythmics) ^{[S1 p14-15]}

• In select patients, catheter ablation may be used even as the first step ^{[S1 p14, p18]}.
• Flecainide and propafenone (Class IC): start flecainide 50-75 mg twice daily (max 150 mg twice daily); propafenone 150 mg three times daily (max 300 mg three times daily). Not for ischemic heart disease or prior heart attack, heart failure or LVEF 40% or lower, Brugada syndrome, advanced conduction disease, marked slow heartbeat, or LVH (left ventricular hypertrophy) with repolarization changes. Combine with an AV-nodal blocker. Stop or reassess if QRS widens by more than 25% or PR is over 200 msec ^{[S1 p14-15]}.
• Sotalol: start 40 mg twice daily (max 160 mg twice daily). Caution or avoid with a long QTc, severe kidney impairment (CrCl below 40 mL/min), age over 75, LV dysfunction (LVEF 40% or lower), LVH, women and potassium-losing diuretics. Stop if QTc rises by more than 25% or reaches 500 msec or more ^{[S1 p14-15]}.
• Dronedarone: 400 mg twice daily. Not for recent decompensated heart failure, LVEF 40% or lower, or long-standing persistent or permanent AF. Use caution with digoxin. Stop if QTc is 500 msec or more or rises more than 25% ^{[S1 p14-15]}.
• Amiodarone: load 400 mg twice daily for 1 week, then 400 mg daily for 2 weeks (or 400 mg daily for 1 month), then maintenance 100-200 mg daily. CCS says to think about other options or ablation rather than long-term amiodarone because of its many side-effects outside the heart ^{[S1 p14-15]}.
• Daily-life example: a patient with heart failure and AF cannot take flecainide (it can be dangerous with weak heart muscle). Amiodarone is the usual drug choice.

3.3 "Pill-in-the-pocket" (PIP) ^{[S1 p17]}

• For people with sustained AF episodes (about 2 hours or more) that happen less often than monthly, with no severe symptoms during an episode and a good understanding of instructions.
• Take an AV-nodal blocker first (diltiazem 60 mg, verapamil 80 mg or metoprolol tartrate 25 mg), then 30 minutes later flecainide (300 mg if 70 kg or more; 200 mg if under 70 kg) or propafenone (600 mg if 70 kg or more; 450 mg if under 70 kg). Rest sitting or lying for 4 hours or until the episode ends.
• The first dose must be tried under observation (telemetry for at least 6 hours). Go to the emergency department if AF lasts 6-8 hours, if the person feels unwell, if there is a second episode within 24 hours (no second PIP dose within 24 hours), or if there are severe symptoms.
• Not for: significant structural heart disease (for example LVEF below 50%, active ischemia, severe LVH), QRS over 120 msec or PR over 200 msec or pre-excitation, sinus node disease or advanced AV block, systolic blood pressure below 100 mmHg, or past intolerance.

3.4 Cardioversion and anticoagulation ^{[S1 p29-31]}

• Planned cardioversion (shock or drugs): give therapeutic anticoagulation for at least 3 weeks before, or do a TEE (transesophageal echocardiogram) to rule out a clot, and continue anticoagulation for at least 4 weeks after. After the 4 weeks, long-term therapy follows CHADS-65.
• Cardioversion without the 3 weeks can be considered only for NVAF with clear onset within 12 hours and no recent stroke/TIA, or onset 12-48 hours with CHADS2 below 2, or an unstable patient. Start the anticoagulant as soon as possible, ideally before.
• Use a DOAC when the anticoagulant will be short (under 2 months) ^{[S1 p31]}.
• Catheter ablation is recommended when symptoms continue after a proper antiarrhythmic trial and rhythm control is still wanted (strong recommendation) ^{[S1 p18]}.

Must remember for the exam: LVEF 40% or lower: beta-blocker, add digoxin, not diltiazem/verapamil; flecainide and propafenone are NOT for heart failure, coronary disease or low LVEF; 3 weeks before and 4 weeks after cardioversion.

4. Choosing the anticoagulant (Canada first)

• Canada: for NVAF, most patients should get a DOAC (apixaban, dabigatran, edoxaban or rivaroxaban) instead of warfarin (strong recommendation). In trials DOACs were as good as or better than warfarin for stroke, had similar major bleeding and less bleeding inside the skull ^{[S1 p20; S2 p2]}.
• Practical DOAC wins: fixed doses, no routine INR testing, few drug interactions, no food interactions ^{[S2 p2]}.
• DOAC downsides: kidney clearance (dose changes needed), and reversal agents are limited for factor Xa drugs ^{[S2 p2]}.
• No head-to-head trials between DOACs, so no DOAC is proven better than another. Pick by stroke risk, bleeding risk and other conditions (kidney disease, past stroke) ^{[S2 p3; S10 p7]}.
• Warfarin is still the drug of choice when AF comes with a mechanical heart valve or moderate to severe mitral stenosis (valvular AF). DOACs are not recommended or approved in valvular AF ^{[S2 p6; S10 p2]}.
• Dabigatran is contraindicated with mechanical valves ^{[S8 p3]}.
• After a bioprosthetic (tissue) valve, a DOAC can be used once the early high-risk period has passed ^{[S10 p2]}.
• Also think about warfarin when kidney function is very poor (CrCl below 15 mL/min) because DOAC labels do not support use there, and when cost, adherence or a drug interaction makes a DOAC a poor choice ^{[S2 p3; S1 p21]}.

4.1 DOAC properties side by side ^{[S10 p4]}

• Onset: all four act within 1-3 hours of a dose ^{[S10 p4]}.
• Memory trick: "Dabigatran is the Drain-by-kidney drug (80%)" and "Rivaroxaban Rides with food". Dabigatran blocks Thrombin (IIa); the others block factor Ten (Xa).

4.2 Doses for AF and how to adjust them

Apixaban (Eliquis) ^{[S6 p1; S13 p9; S1 p21]} - 5 mg twice daily. Use 2.5 mg twice daily when at least 2 of these 3 are present: age 80 or older, body weight 60 kg or less, serum creatinine 133 micromol/L or more. - No adjustment for mild or moderate kidney impairment, even at CrCl 25-30 mL/min, unless two of the criteria are met. At CrCl 15-24 mL/min no dosing advice is given (very little data). Not recommended below 15 mL/min or on dialysis (label). - Food does not matter for this drug; the tablet may be crushed in water or applesauce ^{[S6 p2]}.

Rivaroxaban (Xarelto) ^{[S7 p2; S14 s4; S2 p3]} - 20 mg once daily with food if CrCl is above 50 mL/min. 15 mg once daily with food if CrCl 30-49 mL/min (Canadian label). At CrCl 15-29 mL/min, CCS 2020 also uses 15 mg daily, with caution. Avoid below 15 mL/min. - 15 mg and 20 mg tablets must be taken with food to absorb well.

Dabigatran (Pradaxa) ^{[S8 p1; S15 p30]} - 150 mg twice daily for most people. 110 mg twice daily for age 80 or older, or age 75 or older with one or more bleeding risk factors (for example recent bleed, moderate kidney impairment, an NSAID, antiplatelet, SSRI/SNRI (selective serotonin reuptake inhibitor / serotonin-norepinephrine reuptake inhibitor) or a P-glycoprotein inhibitor). - Contraindicated when CrCl is below 30 mL/min (label). No automatic dose change for CrCl 30-50 mL/min. - Capsules must be swallowed whole (never opened, crushed or chewed; this would raise exposure). Keep in the original blister pack. Do not give through a feeding tube ^{[S8 p3; S10 p1-2]}. - Stomach upset (dyspepsia) in up to 10% of users; taking it with meals helps ^{[S8 p2; S10 p1]}.

Edoxaban (Lixiana) ^{[S17 p6; S9 p1; S2 p3]} - 60 mg once daily. Drop to 30 mg once daily if ONE OR MORE of these apply: CrCl 15-50 mL/min, body weight 60 kg or less (132 lb), or use of a P-glycoprotein (P-gp) inhibitor other than amiodarone and verapamil ^{[S17 p6; S9 p1]}. Not recommended below CrCl 15 mL/min or on dialysis ^{[S17 p6]}. - The Health Canada Lixiana monograph (Servier Canada, revised 5 January 2024) agrees with Thrombosis Canada on these three 30 mg triggers. Switching from warfarin: start edoxaban when INR is 2.5 or lower ^{[S17 p7]}.

Kidney function checks: measure CrCl at least once a year for all DOAC patients, and more often when kidney function is lower or the person is ill: about every 6 months at CrCl 30-49 mL/min, every 3 months at CrCl 15-30 mL/min with rivaroxaban ^{[S2 p3; S6 p2; S10 p5]}. - Use the Cockcroft-Gault CrCl (not the lab eGFR) for DOAC dosing (the labels give the Cockcroft-Gault formula) ^{[S13; S14; S15]}.

Obesity note: dabigatran has little data when BMI is above 40 kg/m2 or weight above 120 kg; use a DOAC with more data (rivaroxaban or apixaban) or warfarin ^{[S8 p3]}.

Daily-life example: Mr. K, 82, weighs 58 kg, creatinine 140 micromol/L, no other problem. He meets all 3 apixaban reduction criteria, so 2.5 mg twice daily. His neighbour, 70, 85 kg, creatinine 90, gets 5 mg twice daily.

4.3 Warfarin: what to know ^{[S3; S4; S16]}

• Warfarin lowers the liver's ability to make working clotting factors II, VII, IX and X (and the natural anticoagulants protein C and S) ^{[S3 p1]}. It is a vitamin K antagonist (VKA).
• AF target: INR (International Normalized Ratio) 2.0-3.0, aim for 2.5. Mechanical mitral valve: target 3.0 (range 2.5-3.5) ^{[S3 p2]}.
• Start: a usual start is 5 mg daily. Use 1-2 mg daily in frail, underweight patients or those of Asian descent. Dose needs vary hugely (under 1 mg to over 20 mg a day) ^{[S3 p2]}.
• Warfarin takes days to work: the first INR after the first dose should be no earlier than 2-3 days. In AF, no heparin bridging is needed when starting warfarin (bridging is needed for acute VTE) ^{[S3 p1-2]}.
• Once stable, INR checks can be spread out: usually about monthly, some every 12 weeks. Too-frequent checks and big dose swings make control worse. Good control = time in therapeutic range (TTR) above 60% ^{[S3 p3; S4 p1]}.
• Bleeding is the main harm: about 1-2% major bleeding per year, minor bleeding 10-20% per year. Rare effects: hair loss and rash ^{[S3 p4]}.
• Diet: no foods are forbidden. Keep vitamin K intake steady and the diet regular; strict vitamin K avoidance can make the INR less stable. Do not tell people to eat less vitamin K ^{[S3 p4; S4 p4]}.
• Drug interactions:
• Antiplatelets more than double the bleeding risk, so use them with warfarin only with a clear reason. NSAIDs also raise bleeding risk and need a risk-benefit check; if an NSAID is needed, celecoxib, or an NSAID plus a PPI (proton pump inhibitor), lowers stomach bleeding risk ^{[S3 p4]}.
• Antibiotics usually raise INR. Others that raise INR: azole antifungals (fluconazole, voriconazole), amiodarone, fenofibrate, acetaminophen above 1 g a day, and thyroid hormone dose changes (full effect over 4-6 weeks). Atorvastatin and pravastatin are least likely to interact ^{[S4 p5]}.
• Drugs that lower INR: phenytoin, carbamazepine, barbiturates, rifampin, azathioprine, trazodone; green tea, ginseng and St. John's wort among products ^{[S4 p4]}.
• After adding a new interacting drug, check the INR in 3-4 days, then adjust. Few drugs must be avoided with this approach ^{[S3 p4]}.
• Pregnancy and breastfeeding: warfarin crosses the placenta and can harm the baby; avoid in pregnancy except in some women with high-risk mechanical valves who are under specialist care. Warfarin is safe in breastfeeding ^{[S3 p5]}. See the label-versus-guideline table in section 11.
• Good habits: keep a log of INR and doses, use one tablet strength where possible, give clear written information, and recheck the INR more often during illness (infection, diarrhea, vomiting, heart failure) ^{[S3 p3-4]}.

4.4 Out-of-range INR (target 2.0-3.0) ^{[S4 p2-4]}

This ladder is for non-bleeding patients. It is the American Society of Hematology 2014 nomogram figure reprinted in Thrombosis Canada v65 (Figure 1) and is a guide only; it does not replace clinical judgment ^{[S4 p2-3]}. Separate text in the same guide gives specific advice for INR above 4.5 and under 10 (see the bullet below the table).

• First look for the cause: missed or extra doses, new drugs (including acetaminophen), supplements, antibiotics, diet changes, alcohol or cannabis, illness ^{[S4 p1-2]}.
• One slightly off INR (about 0.5 out of range) in a stable patient: keep the same dose and repeat in 1-2 weeks, or change by half to one dose once and repeat in 1-2 weeks. Change the weekly dose after two out-of-range INRs in a row in the same direction with no clear cause ^{[S4 p2]}.
• INR above 4.5 and under 10 with no clinically relevant bleeding: Thrombosis Canada advises holding warfarin alone, with no vitamin K. For this range (INR about 5 to 9) follow this text, not the 4.1-8.9 row of the ladder ^{[S4 p3]}. Vitamin K can be given when INR is above 10, depending on the person ^{[S4 p3]}.
• Note: people who are underdosed are not safer. Bleeding risk is similar at INR 1.5-2.0 and 2.0-3.0, but clot risk rises quickly below 2.0. Aiming for 2.5 reduces underdosing ^{[S4 p4]}.
• Do not tell patients to eat less vitamin K to "raise" the INR; keep the diet steady ^{[S4 p4]}.
• High-risk patients (for example mechanical valve, recurrent VTE) may need temporary LMWH when INR is too low ^{[S4 p3]}.

4.5 Switching anticoagulants

• Warfarin to a DOAC: stop warfarin, then wait until INR is below 2.0 for dabigatran or apixaban, and 2.5 or lower for rivaroxaban or edoxaban, before the first DOAC dose. DOACs work within 1-3 hours, but warfarin wears off slowly. If INR cannot be checked, waiting 2-3 days after the last warfarin dose is reasonable ^{[S10 p5; S14 s4; S15 p31; S13 p31]}.
• DOAC to warfarin (Health Canada labels): there is a risk of too little protection, so overlap them.
• Apixaban or rivaroxaban: continue the DOAC together with warfarin until INR is 2.0 or more; warfarin can be started at usual doses for the first 2 days without INR tests; check the INR just before the next DOAC dose (at least 12 hours after apixaban, 24 hours after rivaroxaban when checking after stopping) ^{[S13 p31; S14 s4]}.
• Dabigatran: start warfarin 3 days before stopping dabigatran if CrCl is 50 mL/min or more, and 2 days before if CrCl is 30 to under 50 mL/min ^{[S15 p31]}.
• DOAC INR readings do not show how strong the DOAC is. INR is only valid for warfarin ^{[S13 p31]}.

Must remember for the exam: DOAC first choice in NVAF; warfarin for mechanical valve or moderate-severe mitral stenosis; INR target 2.0-3.0; apixaban 2.5 mg needs 2 of 3 (age 80+, 60 kg or less, creatinine 133+); dabigatran 110 mg at age 80+, contraindicated CrCl under 30; rivaroxaban with food; edoxaban 30 mg for CrCl 15-50, weight 60 kg or less or potent P-gp inhibitor.

5. Patients with heart artery disease or stents

• Stable coronary or arterial disease with an anticoagulant indication (age 65+ or CHADS2 1+): anticoagulant alone, not anticoagulant plus aspirin. Adding an antiplatelet raises bleeding and deaths without much gain ^{[S1 p26]}. "Stable" means no acute coronary syndrome in the past 12 months.
• After PCI (percutaneous coronary intervention) or ACS (acute coronary syndrome) in AF patients: use dual pathway therapy = anticoagulant plus clopidogrel (the preferred P2Y12 inhibitor), for 1 to 12 months. When risk of clots in the stent is high, a short triple therapy (anticoagulant + clopidogrel + ASA) lasts from 1 day to 1 month. Beyond 1 year after PCI, use the anticoagulant alone at standard stroke-prevention doses ^{[S1 p24, p28]}.
• Prefer a DOAC over warfarin with antiplatelets. If warfarin is used, aim for the lower INR range (2.0-2.5). Avoid prasugrel and ticagrelor with an anticoagulant when possible; consider a PPI; avoid NSAIDs; control blood pressure ^{[S1 p25]}.
• Daily-life example: a man 8 months after a stent for AF takes apixaban plus clopidogrel. A year later the clopidogrel stops and apixaban continues alone.

6. Planned surgery or procedures (peri-procedure)

6.1 Warfarin ^{[S5 p1-4; S1 p22-23]}

• Most procedures need warfarin stopped 5 days before. Minimal-bleed procedures can go ahead without stopping warfarin: simple dental extraction (1-2 teeth), root canal, cataract surgery (usually with topical anesthetic) ^{[S5 p3, p5]}.
• For dental work, tranexamic acid mouthwash (5 mL just before, then 2-3 times a day until bleeding stops) helps ^{[S5 p5]}.
• Bridging (a short-acting heparin, usually LMWH, while warfarin is off) is suggested only for high thrombotic risk: mechanical mitral valve, older mechanical aortic valve, rheumatic valve disease, AF with CHADS2 5-6, stroke/TIA/systemic embolism or VTE within the last 3 months, and some severe thrombophilias. It is optional at intermediate risk (AF with CHADS2 3-4, or VTE 3-12 months ago) and not recommended at low risk (AF with CHADS2 0-2, or VTE more than 12 months ago) ^{[S5 p2]}.
• Bridging pattern (high-risk patients): stop warfarin 5 days before; start therapeutic LMWH about 3 days before surgery; the day before surgery give half the daily dose (or only the morning dose for twice-daily drugs); resume warfarin after surgery when the patient is drinking fluids; restart therapeutic LMWH according to bleeding risk. Example doses: enoxaparin 1 mg/kg twice daily or 1.5 mg/kg once daily ^{[S5 p2, p4]}.
• Bridging adds about 2% major bleeding and 10-15% minor bleeding, so use it carefully ^{[S5 p3]}.
• If INR on the day before surgery is above 1.5, consider vitamin K 1-2 mg by mouth (selected patients) ^{[S5 p4]}.
• Daily-life example: a 72-year-old with AF, CHADS2 2, needs a hernia repair. Stop warfarin 5 days before, no bridging, restart when able to take fluids.

6.2 DOACs (PAUSE-style plan, no bridging) ^{[S12 p1-6; S1 p23]}

• DOAC drugs act and wear off quickly, so no heparin bridging is needed. No routine blood tests before surgery are needed. The PAUSE study (3,007 AF patients on DOACs) showed low major bleeding (below 2%) and low stroke (below 1%) with this plan ^{[S12 p2]}.
• Last dose before surgery:

• Nothing is taken on the day of surgery. Minimal-bleed procedures (minor dental, cataract, minor skin): the DOAC may be continued, or skipped that day, or the dose delayed 4-6 hours afterwards ^{[S12 p2-3]}.
• Restart: about 24 hours after low or moderate bleed-risk procedures, 48-72 hours after high bleed-risk procedures, and only when bleeding has stopped. Restart carefully after major surgery because the full therapeutic dose is stronger than a prevention dose ^{[S12 p4-6; S1 p23]}. CCS also suggests thinking about holding anticoagulation for the first 72 hours after cardiac surgery ^{[S1 p23]}.
• Dabigatran needs longer holds because 80% is cleared by the kidney ^{[S12 p3]}.
• Memory trick: "Two days for the small, three days for the big" (last DOAC dose 2 days before low-moderate risk, 3 days before high risk).

6.3 Urgent and emergency procedures ^{[S1 p22]}

• Urgent (within hours to days): if possible wait 12-24 hours. For warfarin, vitamin K 2.5-5 mg IV may be given. For dabigatran, idarucizumab can be considered if the procedure cannot wait.
• Emergency (within minutes to hours): for warfarin, vitamin K 5-10 mg IV and consider prothrombin complex concentrate (PCC) or activated PCC. For a DOAC, use the antidote if available (idarucizumab for dabigatran), otherwise PCC or activated PCC. Tell patients about the small clot risk of PCC ^{[S1 p22]}.

Must remember for the exam: warfarin off 5 days, bridging only for high thrombotic risk; DOAC 2 days off (low-moderate), 3 days off (high), no bridging; restart 24 h (low-moderate) or 48-72 h (high).

7. Bleeding and reversal

7.1 Warfarin

• For emergency reversal, give IV vitamin K together with a 4-factor prothrombin complex concentrate (Octaplex, Beriplex). Oral vitamin K can be used for very high INR without emergency. There is no role for subcutaneous vitamin K ^{[S3 p5; S1 p22]}.

7.2 DOACs (Thrombosis Canada) ^[S11]

• DOACs leave the body quickly: half-lives are about 10-12 hours with normal organs, and a lot is cleared within 24 hours ^{[S11 p1]}.
• Minor bleeding (bruising, mild nosebleed): continue the DOAC and monitor; check dose and drug interactions ^{[S11 p1]}.
• Clinically relevant non-major bleeding (for example a stable stomach bleed, nosebleed needing care, blood in urine): hold the DOAC, local measures (pressure, packing), check blood count, kidney and liver tests ^{[S11 p2]}.
• Major or life-threatening bleeding (for example in the brain, spine, retroperitoneum, or with unstable blood pressure): hold the DOAC, resuscitate, local measures, urgent expert help, and consider specific reversal agents ^{[S11 p2-3]}.
• Lab clues: a normal INR or aPTT does NOT rule out a DOAC effect. An abnormal one suggests a meaningful drug level. A normal thrombin time rules out dabigatran ^{[S11 p2-3]}.
• Dabigatran: idarucizumab (Praxbind) 5 g IV (two 2.5 g vials) works within minutes. If it is not available, consider a 4-factor PCC or activated PCC. Hemodialysis can remove about 65% of dabigatran after 4 hours ^{[S11 p4]}.
• 4-factor PCC and activated PCC are clotting-factor concentrates, not antidotes. They supply clotting factors (a 4-factor PCC contains factors II, VII, IX and X ^{[S18 p1]}; Thrombosis Canada names II and X as the factors that may reduce DOAC-related bleeding) to help stop bleeding, but they do not lower the DOAC level or cancel its effect ^{[S11 p5]}.
• Apixaban, rivaroxaban (and edoxaban): andexanet alfa (Ondexxya) is indicated in Canada for rivaroxaban or apixaban when life-threatening or uncontrolled bleeding needs rapid reversal. It is not approved by Health Canada for edoxaban. In studies it raised the chance of clots (for example 18% thrombotic events in 30 days in one trial) ^{[S6 p3; S10 p4; S11 p5]}. 4-factor PCC can be given when no antidote is available (for example 2000 units fixed dose, or 25-50 units/kg up to 3000 units) ^{[S11 p5]}.
• Tranexamic acid: no direct proof in DOAC bleeding; it may be an add-on, but it is not recommended for genitourinary or gastrointestinal bleeding. Recombinant factor VIIa is generally not recommended ^{[S11 p5]}.
• Tell patients PCC and antidotes carry a small clot risk, but uncontrolled bleeding is usually worse ^{[S11 p4-5]}.
• After bleeding stops: review whether anticoagulation should restart, with patient preference, bleeding and clot risk, drug and dose check, kidney and liver tests, and other drugs (antiplatelets, NSAIDs, SSRIs, herbal products). Teach when to seek help ^{[S11 p7]}.

8. Counselling and safety checks at the counter

• DOAC counselling ^{[S10 p1-5]}:
• Missed dose: never double. Thrombosis Canada: carry on with the next scheduled dose. The Health Canada labels differ: apixaban, take it as soon as you remember, then carry on as usual ^[S13]; dabigatran for AF, take it as soon as you remember unless the next dose is less than 6 hours away, then skip it ^[S15]; rivaroxaban 20 mg once daily, take it as soon as you remember on the same day ^{[S14 s4.5]}. Ask the pharmacist. (This point is not tested in the quiz.)
• No routine INR; follow-up at least every 6-12 months with a blood count, kidney function and a medicine review.
• No food interactions. Alcohol: keep to 1 standard drink a day or less (CCS AF pocket guide ^{[S1 p7]}). There is no evidence that grapefruit juice changes DOAC effects.
• Rivaroxaban 15 and 20 mg with food. Dabigatran capsules whole, in the blister pack (a pill box is possible only if the blister stays sealed). Apixaban, edoxaban and rivaroxaban can be crushed.
• Avoid long-term NSAIDs; acetaminophen is preferred for pain or colds. Avoid St. John's wort (lowers DOAC levels). Garlic and turmeric (curcumin) supplements should generally be avoided because they raise bleeding risk.
• PPIs and H2-blockers do not matter clinically, but aluminum, magnesium or calcium antacids lower dabigatran absorption.
• Avoid a DOAC with an epidural catheter or recent spinal puncture ^{[S6 p2]}.
• Not for pregnancy or nursing; apixaban, edoxaban, rivaroxaban and dabigatran cross the placenta ^{[S6 p2; S7 p3; S8 p4; S9 p3]}.
• DOAC interactions to know ^{[S10 p4; S6 p3; S7 p4; S8 p3; S9 p4]}:
• Strong combined P-gp and CYP3A4 inhibitors (azole antifungals such as ketoconazole, itraconazole, voriconazole and posaconazole; ritonavir; cobicistat): contraindicated with apixaban and rivaroxaban in the Health Canada labels ^{[S13; S14]}. Thrombosis Canada says "avoid" for apixaban ^{[S6 p3]}.
• Strong inducers (rifampin, carbamazepine, phenytoin, phenobarbital, St. John's wort): lower DOAC levels; avoid.
• Dabigatran: ketoconazole and dronedarone contraindicated; take dabigatran at least 2 hours before verapamil or quinidine; SSRIs and SNRIs raise bleeding.
• Rivaroxaban plus nirmatrelvir/ritonavir (Paxlovid): not recommended; Thrombosis Canada advises holding rivaroxaban for 24 hours before starting Paxlovid and restarting it 2 days after the Paxlovid course ends, with a safer alternative in between (for example edoxaban 30 mg daily for AF) ^{[S7 p4]}.
• Warfarin counselling ^{[S3 p3-4; S4 p1-4]}: same time every evening, one tablet strength if possible, keep a dose and INR log, steady diet, report new drugs or illness, avoid heavy drinking sessions (one big binge can raise INR), tell all providers and dentists, and learn bleeding signs.
• Never stop an anticoagulant suddenly without medical advice: stopping early raises the clot and stroke risk (boxed warning in the Health Canada labels) ^{[S13; S14; S15]}.
• Do not combine two anticoagulants. DOACs are contraindicated with active clinically significant bleeding, and dabigatran with a bleeding disorder or lesions at risk of bleeding ^{[S15 p3-4]}. Rivaroxaban should be avoided in moderate or severe liver impairment (Child-Pugh B or C) ^{[S7 p4]}.
• Signs to report for any anticoagulant: black or bloody stool, blood in urine, vomiting blood, nosebleeds that will not stop, severe headache, a fall with a head strike, big bruises.
• Pharmacist role: confirm the right drug and dose (age, weight, creatinine, CrCl), screen interactions (including OTC NSAIDs, herbals), check adherence, arrange yearly follow-up labs, and advise before surgery. Thrombosis Canada offers a DOAC monitoring checklist for pharmacists ^{[S6 p2]}.

9. Canada vs US (Canada wins on the exam)

• The 2023 US guideline text itself was not opened; U1 is a summary page.

10. Easy memory tricks in one place

• Types of AF: Paroxysmal = Passes in a week. Persistent = Past a week. Permanent = Parked for good.
• CHADS2: Congestive heart failure, Hypertension, Age 75 or older, Diabetes, Stroke or TIA (2 points).
• CHADS-65: 65 or older, or any CHADS2 factor: blood thinner.
• Apixaban cut-down: 2 of 3 (age 80 or more, weight 60 kg or less, creatinine 133 or more).
• "Dabigatran Drains through the kidney (80%)" and is contraindicated below CrCl 30.
• "Rivaroxaban Rides with food" (15 and 20 mg).
• Idarucizumab = antidote for dabigatran. Andexanet alfa = antidote for apixaban and rivaroxaban.
• Warfarin 5 days off before surgery; DOAC 2 days off (small surgery) or 3 days (big surgery).

11. Label vs guideline and Canada vs Canada (both shown; none of these is used in the quiz)

• Exam tip: for dose and contraindication questions use the Health Canada label. For choice of therapy, use the CCS guideline and Thrombosis Canada.

12. Ten original practice MCQs

Q1. A 58-year-old man has high blood pressure and a first AF episode. He is not diabetic and has no stroke history. By the CHADS-65 approach, what is best? - A. No antithrombotic - B. Aspirin 81 mg daily - C. A DOAC - D. Warfarin, never a DOAC

Q2. An 81-year-old woman weighs 56 kg and has a serum creatinine of 142 micromol/L. Which apixaban dose is best for AF? - A. 2.5 mg twice daily - B. 5 mg twice daily - C. 10 mg twice daily - D. 5 mg once daily

Q3. AF with moderate to severe mitral stenosis. Best anticoagulant? - A. Apixaban - B. Dabigatran - C. Rivaroxaban - D. Warfarin

Q4. Warfarin patient with an INR of 3.8 and no bleeding (target 2.0-3.0). Best step in the Thrombosis Canada algorithm? - A. Hold 0-1 dose, lower the weekly dose 10-15%, repeat INR in 1 week - B. Give vitamin K by IV injection and recheck the INR in 1 hour - C. Increase the weekly dose by 10-15% and repeat the INR in 2 weeks - D. Stop warfarin for good and switch to aspirin

Q5. Which drug is used for dabigatran reversal? - A. Andexanet alfa - B. Idarucizumab - C. Protamine - D. Vitamin K

Q6. Planned minor surgery (low-moderate bleed risk) in a patient taking apixaban 5 mg twice daily. When is the last dose? - A. The morning of surgery - B. The night before surgery - C. 2 days before surgery - D. 7 days before surgery

Q7. Which drug should be avoided in a patient with AF, heart failure and LVEF 35%? - A. Amiodarone - B. Flecainide - C. Digoxin for rate control - D. Bisoprolol for rate control

Q8. Rivaroxaban 20 mg once daily for AF should be taken how? - A. With food - B. On an empty stomach - C. Only at bedtime without food - D. Only with antacid

Q9. Which statement about warfarin and diet is right? - A. Avoid all vitamin K foods - B. Keep the vitamin K intake regular and steady - C. Eat only leafy greens - D. No diet advice at all

Q10. A patient on warfarin needs a short course of an antibiotic (for example ciprofloxacin). What is best? - A. Stop warfarin until the antibiotic course is finished - B. Ignore it, antibiotics never change the INR - C. Double the warfarin dose during the antibiotic - D. Check INR in 3-4 days and adjust

13. Answers and explanations

1. C. Age under 65 but with a CHADS2 factor (high blood pressure) means an OAC, and a DOAC is preferred ^{[S1 p19, p20; S2 p4]}.
2. A. Two of three criteria (age 80 or more, weight 60 kg or less, creatinine 133 or more) meet the dose cut-down; she meets all three ^{[S6 p1; S13 p9]}.
3. D. Valvular AF (moderate to severe mitral stenosis) needs warfarin; DOACs are not recommended ^{[S2 p6; S1 p2]}.
4. A. INR 3.6-4.0: hold 0-1 dose, lower weekly dose by 10-15%, repeat in 1 week ^{[S4 p2]}.
5. B. Idarucizumab (Praxbind) reverses dabigatran ^{[S11 p4]}.
6. C. Low-moderate bleed risk: last apixaban dose 2 days before surgery (skip 2 doses) ^{[S12 p4-5]}.
7. B. Flecainide is not for heart failure or LVEF 40% or lower ^{[S1 p15]}.
8. A. 15 and 20 mg rivaroxaban tablets are taken with food ^{[S7 p3; S10 p1]}.
9. B. Keep vitamin K intake steady; strict avoidance makes INR less stable ^{[S3 p4; S4 p4]}.
10. D. Check INR 3-4 days after adding an interacting drug and adjust the dose ^{[S3 p4]}.

14. Sources (accessed 2026-10-24; Canada first, then US)

Canada

• S1. Canadian Cardiovascular Society (CCS) Atrial Fibrillation Pocket Guide (version AF-2021-03-P2, 2021, posted 2022-05-06), based on the 2020 CCS/CHRS Comprehensive Guidelines for the Management of Atrial Fibrillation (Andrade JG, Macle L, et al. Can J Cardiol 2020;36:1847-1948). https://ccs.ca/wp-content/uploads/2022/05/AF-Gui-Pocket-Guide-2021P2-EN-web.pdf . Library file: canada/guidelines/anticoagulation-thrombosis/AF-Gui-Pocket-Guide-2021P2-EN-web.pdf. This is the newest CCS/CHRS AF guideline content found. Page numbers = printed pages.
• S2. Thrombosis Canada Clinical Guide: Stroke Prevention in Atrial Fibrillation, v68, 17 Jan 2024. Library: ThrombosisCanada-AF-Stroke-Prevention-v68_2026.pdf. https://thrombosiscanada.ca
• S3. Thrombosis Canada: Warfarin, v48, 5 July 2026.
• S4. Thrombosis Canada: Warfarin: Management of Out-of-Range INRs, v65, 15 June 2025.
• S5. Thrombosis Canada: Warfarin: Perioperative Management, v69, 24 June 2026.
• S6. Thrombosis Canada: Apixaban (Eliquis), v78, 2 June 2025.
• S7. Thrombosis Canada: Rivaroxaban (Xarelto), v54, 2 Nov 2025.
• S8. Thrombosis Canada: Dabigatran (Pradaxa), v57, 10 Sept 2026.
• S9. Thrombosis Canada: Edoxaban (Lixiana), v54, 11 July 2026.
• S10. Thrombosis Canada: DOACs: Comparison and Frequently-asked Questions, v79, 1 May 2025.
• S11. Thrombosis Canada: DOACs: Management of Bleeding, v82, 16 Oct 2025.
• S12. Thrombosis Canada: DOACs: Perioperative Management, v90, 29 May 2025.
• S13. APO-APIXABAN (generic of Eliquis) Product Monograph, Apotex, 2025-12-22. https://pdf.hres.ca/dpd_pm/00082920.PDF . Library: Apo-Apixaban_PM_2025-12-22.pdf. The brand Eliquis monograph found online was older (2019), so the newer generic label was used.
• S14. Xarelto (rivaroxaban) Product Monograph, Bayer Inc., authorization 2025-09-23. https://pdf.hres.ca/dpd_pm/00082020.PDF . Cited by section number.
• S15. Pradaxa (dabigatran etexilate) Product Monograph, Boehringer Ingelheim Canada, 2025-04-22. https://pdf.hres.ca/dpd_pm/00080323.PDF
• S17. Lixiana (edoxaban) Product Monograph, Servier Canada Inc., revision 5 January 2024. https://pdf.hres.ca/dpd_pm/00074083.PDF . Library: Lixiana_PM_2024-01-05.pdf. (Canada)
• S18. Beriplex P/N 500 / 1000 (human prothrombin complex, 4-factor PCC) Product Monograph, CSL Behring Canada, revision listed 7 November 2025. https://pdf.hres.ca/dpd_pm/00082797.PDF . Library: Beriplex_PM_2025-11-07.pdf. (Canada)
• S16. Taro-Warfarin Product Monograph, authorization 2026-04-08. https://pdf.hres.ca/dpd_pm/00084195.PDF

United States (extra; secondary summary)

• U1. American College of Cardiology, "2023 Guideline for Diagnosis and Management of Atrial Fibrillation: Key Perspectives" (ten points to remember; summary of the 2023 ACC/AHA/ACCP/HRS guideline), published 2023-11-27. https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2023/11/27/19/46/2023-acc-guideline-for-af-gl-af . The full guideline was not opened.

PEBC reference: PEBC Pharmacist Qualifying Examination Blueprint Ver. 03-2026 (area names only): https://pebc.ca/wp-content/uploads/pdfs/Qual%20EN/Pharmacist_Qualifying_Exam_Blueprint.pdf

15. Unconfirmed / check yourself

• The full 2020 CCS/CHRS AF guideline text was not opened; the 2021 pocket guide (a summary) and Thrombosis Canada guides were used. A newer CCS update could exist on ccs.ca (that site gave an error), but none was found in searches.
• The brand Eliquis monograph (current revision) was not retrieved. Eliquis dosing was checked in the generic apixaban label (S13) and Thrombosis Canada. The Lixiana monograph (S17) was retrieved on 2026-10-24 and confirms the edoxaban doses.
• European guidelines (for example the 2024 ESC guideline) were not read. The US guideline is shown only through a secondary ACC summary page.
• Drug labels for amiodarone, sotalol, flecainide, propafenone, digoxin and the beta-blockers were not opened for this topic. Rate and rhythm doses come from the CCS pocket guide (S1) only; dronedarone has a label in the library that was not re-read.
• The warfarin-to-DOAC INR thresholds are the same in the labels checked (apixaban and dabigatran below 2.0, rivaroxaban 2.5 or lower); edoxaban's threshold (INR 2.5 or lower) is confirmed in the Lixiana label ^{[S17 p7]}.
• Peri-procedure tables for procedures other than dental, cataract and the general scheme (Thrombosis Canada procedure tables A-K) were not used. Neuraxial anesthesia timing rules beyond "high bleed risk" were not studied in detail.
• Time in therapeutic range "above 60%" is Thrombosis Canada's empiric definition of good control.
• Andexanet alfa: current availability and place in practice in Canada may have changed after the guides were written; check Health Canada.
• Doses are for exam study only, not for real patients. Not affiliated with or endorsed by PEBC.

Study aid, not medical advice. Check official sources before any patient decision.

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