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5. SPAF Flashcards

1
Q

Cause of stroke in AF

A

Turbulent flow caused by uncoordinated contraction of fibrillation of left atrium → concentration of clotting factors in left atrial appendage (LAA) → clot formation → embolism of clot → emboli travels to brain → ischemic stroke

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2
Q

What is CHA2D2VASc for?

A

estimate stroke risk

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3
Q

List all the risk factors in CHA2DS2VASc

A

Congestive HF
HTN >140/90 or need antiHTN drugs
Age >=75 yo (x2 score)
DM
Stroke hx/TIA (x2 score)
Vascular disease - hx MI, PAD, aortic plaque
Age 65-74

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4
Q

When to start tx with anticoagulation in SPAF

A

Score 0: no anticoagulants
Score = 1: CONSIDER anticoagulant
Score ≥ 2: START anticoagulant (DOAC > warfarin)

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5
Q

when is warfarin preferred over VKA?

A

mechanical heart valve
moderate to severe mitral stenosis
left ventricular thrombus
antiphospholipid syndrome

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6
Q

can antiplatelet be used in SPAF?

A

NO ANTIPLATELETS

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7
Q

List all the bleeding RF in HASBLED

A

HTN uncontrolled >160mmHg
Abnormal renal/hepatic function
Stroke (hx)
Bleeding hx
Labile INR (unstable or high INRs)
Elderly age >65yo
Drugs (antiplatelet/NSAIDs)/alcohol use (men 14u, female 7u/ week)

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8
Q

What is considered high bleeding risk and what is the management?

A

HASBLED ≥3 = high bleeding risk
Identify and modify risk factors (does not limit/ withhold use of OAC)

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9
Q

Tx of SPAF

A

anticoagulants (DRAWE)

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10
Q

Dabigatran dose in SPAF
renally impaired?

A

150mg BD
110mg BD (≥80yo, concomitant PGP inhibitors, high risk of bleeding)

  • CrCL 30-50ml/min: no dose adjustments unless DDI
  • CrCL <30: CI
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11
Q

Rivaroxaban SPAF dose

A

20mg OD

CrCL 30-50ml/min: 15mg OD
CrCL 15-30: caution
CrCL <15: CI

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12
Q

Apixaban SPAF dose

A

5mg BD
2.5mg BD (any 2 of following: ≥80yo, weight ≤60kg, SCr ≥133mmol/L)

CrCl 30-50ml/min: 5mg BD
CrCL <30: 2.5mg BD

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13
Q

Edoxaban SPAF dose

A

60mg OD
30mg OD (CrCL 30-50ml/min, weight ≤60kg, concomitant verapamil/quinidine/dronedarone)

CrCL 30-50ml/min: 30mg OD
CrCL 15-30: 30mg OD
CrCl <15: not recommended

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14
Q

warfarin for SPAF

A

INR 2.0-3.0, TTR ≥70% (time in therapeutic range)
if TTR <70% switch to DOAC

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15
Q

Renally impaired pt on SPAF what is the tx

A

DOAC preferred over warfarin (in SPAF)

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16
Q

which DOAC is a substrate of CYP450?

A

Rivaroxaban, Apixaban (both 3A4)

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17
Q

which DOAC is a substrate for Pgp?

A

all DOAC (not warfarin)

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18
Q

CI for DOAC use (DDI and illness)

A
  • rifampicin, valproate, St John’s wort, azole
  • sever hepatic impairment, ESRD (CrCl <30), mechanical heart valve, moderate-severe mitral stenosis, LV thrombus
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19
Q

Renal failure pt SPAF tx

A

DOAC preferred over warfarin (better safety and efficacy profile)

20
Q

Elderly SPAF tx

A

DOAC preferred over warfarin (less intracranial haemorrhage, less major bleeding, less stroke)
Elderly: Apixaban preferred

21
Q

underweight and overweight SPAF tx

A
  • Low body weight: dosing adjustments for apixaban and edoxaban (further decrease if renally impaired)
  • High body weight (limited data): rivaroxaban, apixaban
22
Q

Warfarin pgx

A

2C9 and VKORC1

23
Q

what factors does warfarin decrease?

A

Decrease factors II, VII, IX, X, protein C and S (endogenous anticoagulants)

24
Q

how to prevent hypercoagulable state with warfarin initiation

A

Add clexane (LMWH/ enoxaparin) together with warfarin when initiating to prevent hypercoagulable state (~4-5 days)

25
factors affecting warfarin dose
- BSA, age, target INR, race, current thrombosis, current amiodarone use, smokers - PGx: VKORC1, CYP2C9 - indians require higher dose of warfarin
26
warfarin DDI (2C9 inhibitors)
amiodarone, fluconazole, metronidazole
27
warfarin DDI (2C9 inducers)
carbamazepine, enzalutamide, phenobarbital, rifampicin, st. john’s wort
28
which drugs when used with warfarin requires preemptive dose adjustment of warfarin
Bactrim (sulfamethxazole, trimethoprim) Ciprofloxacin Metronidazole?? Amiodarone (decr dose by 30-50%) Fluconazole (decr dose by 10-20%) Rifampicin (incr dose by 1.5-2x)
29
Alcohol binge effect on INR
increase CYP450 inhibition → increase INR (INR “blip”)
30
Chronic alcoholism effect on INR
CYP450 induction → increase warfarin metabolism → decrease INR
31
Increase physical activity effect on INR
increase warfarin metabolism → decrease INR
32
smoking effect on INR
CYP450 induction → increase warfarin metabolism → decrease INR
33
liver impairment effect on warfarin
decrease clotting factor synthesis & warfarin metabolism → increase INR
34
fluid retention effect on INR
- Liver congestion: decrease metabolism of warfarin → increase INR (more impactful) - Gut edema: malabsorption of warfarin → decrease INR
35
fever effect on INR
increase INR (increase turnover/metabolism of clotting factor = less clotting factors)
36
thyroid disease effect on INR
- Hyperthyroidism: increase clotting factor turnover → increase INR - Hypothyroidism: decrease clotting factor turnover → decrease INR
37
warfarin target INR
- INR 2.5 (2-3) - DVT/PE: usually 3mths tx if no CI/ chronic RF - SPAF, severe mitral stenosis: lifelong - Bioprosthetic: 3-6mths after surgery - LV thrombus: 3mths tx - INR 3 (2.5-3,5) - Mechanical heart valve
38
switching warfarin to DOAC
Stop warfarin for 3 days → when INR below 2, start DOAC
39
switching DOAC to warfarin
- no need hold DOAC (use for 3-5 days) - At day 3-5: measure INR → INR >2 stop DOAC, continue warfarin
40
when is the first follow up?
1 mth
41
subsequent follow up duration
- Yearly - Every 4mths: ≥75yo (especially on dabigatran or edoxaban) or frail - CrCl/10 mths: eGFR/CrCl ≤60ml/min
42
what to monitor
- Adherence - Thrombo-embolism - Bleeding - Side effects - DDI with other medications - Assess and minimise modifiable risk factors for bleeding (uncontrolled HTN, other anticoagulant/antiplatelets, labile INR, excessive alcohols, falls) - Assess for optimal DOAC choice and dosing
43
DOAC reversal tx (mild)
delay or discontinue next dose
44
DOAC reversal tx (Non-life threatening major bleeding)
delay or discontinue next dose + supportive measures (on dabigatran) idarucizumab/ hemodialysis
45
DOAC reversal tx (Life threatening major bleeding)
(Darbi) IV idarucizumab 5g (expensive) (FXa inhibitors) Andexanet alpha otherwise: - PCC (prothrombin complex concentrate) - aPCC (activated PCC)
46
warfarin reversal
no major bleeding - INR <4.5: investigate - INR >4.5: consider vit K major bleeding: IV vit K minor bleeding: assess bleeding, consider vit K

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