IC5 SPAF

Question 1

Explain how AFib can result in stroke

Answer 1

AFib in the left atrial appendage can lead to clot formation due to turbulent blood flow

Clot in the heart can embolize into left ventricle => aorta => cerebral circulation

Embolus in cerebral artery blocks blood flow to the brain, leading to brain tissue death and stroke

Question 2

Why are DOACs recommended over VKAs in SPAF?

Answer 2

• Better outcomes in terms of prevention of stroke or systemic embolism, intracranial hemorrhage, and major bleeding outcomes (as effective in reducing AF-related strokes and systemic embolism, a/w fewer ICH. but incr GI bleed)
• noninferior efficacy, less major bleeding
• DOAC benefit preserved across deteriorating renal function (unlike Warfarin - a/w greater deterioration of renal function due to VKA-associated nephropathy, vascular calcification, glomerular hemorrhage)
• Less DDIs
• No need for monitoring (unlike warfarin - narrow TI, require frequent titration)

Other:

• pt w less than 6 out of 10 INR readings within therapeutic range (labile INR) while on Warfarin

Question 3

When is warfarin still required?

Answer 3

• Valvular AF (Mechanical/Prosthetic heart valves, mod-severe mitral stenosis)
• Left ventricular thrombus
• APS

Question 4

In what situation might Warfarin be favoured over DOAC?

Answer 4

• Pt who can maintain 6 out of 10 INR readings within therapeutic range (labile INR) while on Warfarin
• Pt unable to tolerate side effects of DOAC
• Pt with mod-severe liver or renal impairment
• Pt with clinically significant DDI with DOAC

Question 5

Ischemic stroke risk scoring: CHA2DS2-VASc score

Answer 5

• Congestive HF (1)
• HTN (1)
• Age 75 or older (2)
• DM (1)
• Previous stroke, TIA, or thromboembolism (2)
• Vascular disease e.g., MI, PAD, aortic plaque (1)
• Age 65-74 (1)
• Sex - Female (1)

Question 6

Based on CHA2DS2-VASc score, when to initiate OAC for SPAF?

Answer 6

Score of >=2 in men, and >= 3 in women

Question 7

HASBLED score to estimate bleeding risk

Answer 7

• HTN >160mmHg
• Abnormal renal function / liver function
• Stroke (history)
• Bleeding (history or predisposition)
• Labile INR
• Elderly >65yo
• Drugs (e.g., antiplatelets, NSAIDs) / Alcohol (>=8 units per week)

Question 8

How is HASBLED score used to determine use of anticoagulants in SPAF?

Answer 8

• Identify non-modifiable factors, and address modifiable risk factors (e.g., control BP, stop concomittant antiplatelet)
• Score is poorly correlated with actual bleeding, hence high bleeding risk score is NOT a reason to withhold OAC
• Pt identified to have high bleeding risk should be scheduled for early and more frequent reviews and follow-up

Question 9

ABC pathway of SPAF

Answer 9

Avoid stroke

• Identify low-risk patients
• Offer SPAF to those with >=1 risk factors (start if >=2)
• Decide on OAC

Better symptom control

• Person-centred and symptom-directed decisions on rate vs rhythm control (rate control more impt)

Cardiovascular and other comorbidities or risk factors

• Manage HTN, HF, DM, cardiac ischemia, sleep apnea
• Lifestyle changes - weight, exercise, alcohol
• Psychological morbidity

Question 10

What might be used for SPAF if pt has major bleeding, and cannot use OAC

Answer 10

Left atrial appendage (LAA) occlusion

• Watchman device implanted to catch clot and prevent clot from entering circulation

Question 11

[SPAF dosing + renal adjustments]
- Apixaban

Answer 11

5mg BD

2.5mg BD for any 2 of the following:

• age >=80yo
• weight =<60kg
• SCr >= 1.5mg/dL or 132.6mmol/L

RENAL ADJ:
CrCl 15-29ml/min: 2.5mg BD
CrCl <15ml/min: NO INFO
HD: 5mg BD approved by FDA

Question 12

[SPAF dosing + renal adjustments]
- Rivaroxaban

Answer 12

20mg per day

RENAL ADJ:
CrCl 30-50ml/min: 15mg per day
CrCl 15-30ml/min: 15mg OD use with caution
CrCl <15ml/min: Contraindicated

Question 13

[SPAF dosing + renal adjustments]
- Edoxaban

Answer 13

60mg per day

30mg per day if any of the following:

• CrCl 30-50ml/min
• weight =<60kg
• concomitant PGP inhibitors: verapamil, quinidine, dronedarone

RENAL ADJ:
CrCl 30-50ml/min: 30mg per day
CrCl 15-30ml/min: 30mg per day
CrCl <15ml/min: not recommended

CrCl >95ml/min: avoid due to incr risk of stroke

Question 14

[SPAF dosing + renal adjustments]
- Dabigatran (most renally cleared)

Answer 14

150mg BD

110mg BD if >=80yo, or use of PgP inhibitors, or high risk of bleeding

RENAL ADJ:
CrCl >50ml/min: 150mg BD, 110mg BD if >80yo or high bleeding risk
CrCl 30-50ml/min: same as above, but 75mg BD if DDI with potent PGP inhibitors
CrCl <30ml/min: contraindicated
CrCl 15-30ml/min: 75mg BD (FDA)

Question 15

Evidence of OAC use for SPAF in elderly

Answer 15

DOACs have better outcomes in terms of prevention of stroke or systemic embolism, intracranial hemorrhage, and major bleeding outcomes as compared to Warfarin

*Unadjusted doses seem to be a/w better outcomes

Question 16

Which two DOACs are preferred in elderly?

Answer 16

Apixaban
Edoxaban

Question 17

Evidence of OAC use for SPAF in low body weight

Answer 17

BW range: 60-120kg

Lower BW require dose adjustment: Apixaban (2.5mg BD), Edoxaban (30mg OD)
(recall =<60kg)

• AVOID Dabigatran, Rivaroxaban

Higher BW (obesity >40kg/m2, weight >120kg) suggest to use with caution: Rivaroxaban, Apixaban

• AVOID Dabigatran, Edoxaban

Question 18

VKA in SPAF

• What are the targets?

Answer 18

INR 2-3 (only if mechanical aortic heart valve: 2.5-3.5)

TTR: 70%

Question 19

[SPAF structure follow up]

Baseline monitoring parameters before OAC initiation

Answer 19

• Blood test (include Hb, renal/liver function, coagulation panel)

Question 20

[SPAF structure follow up]

Interval for follow-up (blood sampling) after initiation of OAC

Blood sampling: Hb/FBC, renal, liver function

Answer 20

First FU after 1 month, subsequent:

• Default: YEARLY
• Every 4 months for >=75yo (esp if on Dabigatran/Edoxaban or frail - renal function decreases with age)
• Every CrCl/10 if CrCl =<60ml/min
• Immediately in the case of intercurrent conditions (esp conditions with potential impact on renal or hepatic functions, e.g., NSAID use, infection, dehydration)

Question 21

[SPAF structure follow up]

Structured follow-up after initiation of OAC

Answer 21

• Adherence
• Thromboembolic S&S (DVT, PE, Stroke)
• Bleeding events (reason for bleed - treat or prevent)
• Side effects (continue or change?)
• Comedications (e.g., NSAIDs)
• Blood sampling (Hb/FBC, renal, liver)
• Assess and minimize modifiable risk factors for bleeding (uncontrolled HTN >160mmHg, concurrent meds, alcohol intake)
• Assess optimal DOAC choice and dosin

Question 22

Switching from DOAC to Warfarin

• INR <2
• INR >=2

Answer 22

• Start VKA while on DOAC (half dose for edoxaban)
• If INR <2, continue DOAC and repeat INR after 1-3days (measure INR before DOAC intake)
• If INR >=2, stop DOAC, repeat INR 1 day after stopping

Question 23

Switching Warfarin to DOAC

• INR <2
• INR 2-2.5
• INR 2.5-3
• INR >=3

Answer 23

• Stop VKA and measure daily INR (the lower the baseline INR< the shorter the time needed to withhold VKA)
• When INR <2, start DOAC immediately
• If INR 2-2.5, start today/tomorrow
• If INR 2.5-3, recheck INR in 1-3 days
• If INR >=3, postpone DOAC, hold warfarin 3 days, TCU day 4 for INR

Question 24

[Bleeding while using NOAC]

• what should be determined first?

Answer 24

• NOAC dose, time of last intake
• Co-medications
• Blood sampling - determine CrCl, hepatic function, WBC
• Rapid coagulation assessment
• Plasma drug levels (if available)

Question 25

[Bleeding while using NOAC] Management of MILD bleeding in pt taking DOAC

Answer 25

- Delay or discontinue next dose => DOAC have relatively short half-life ~12h, easy to reverse effects when discontinued/withhold - Reconsider any concomitant medication - Reconsider choice of NOAC and dosing

Question 26

[Bleeding while using NOAC] Management of NON-LIFE THREATENING MAJOR bleeding in pt taking DOAC

Answer 26

- Delay or discontinue next dose - Add on supportive measures: mechanical compression, surgical/endoscopic hemostasis, fluid replacement, RBC/platelet substitution, adjuvant transexamic acid - Treat any factors/comorbidities contributing to the bleed - Consider reversal agent - idarucizumab for Dabigatran (or consider dialysis to clear Dabigatran)

Question 27

[Bleeding while using NOAC] Management of LIFE-THREATENING/BLEEDING INTO CRITICAL STATE in pt taking DOAC E.g., critical state: into spinal cord, heart, abdominal space etc.

Answer 27

- Delay or discontinue next dose - Add on supportive measures - For Dabigatran: IV Idarucizumab - For FXa inhibitor DOACs: Andexanet alpha (not available in SG) - For DOACs: PCC/aPCC (activated prothrombin complex concentrates)

Question 28

DOAC - unplanned invasive procedure

Answer 28

Determine time to hold off DOAC before invasive procedure Patient factors: - e.g., age, stroke risk, bleeding risk, recent CVD events, medications, renal function - *As renal function worsens, time to hold off increases Surgical factors: - e.g., bleeding risk of procedure, consequence of bleeding

Question 29

Duration of Warfarin in different indications - DVT, PE, thrombus - SPAF - Valvular heart disease - Mechanical heart valve - Bioprosthetic heart valve

Answer 29

DVT: 3m PE: 3m SPAF: lifelong Valvular heart disease (mitral stenosis): lifelong Mechanical heart valve: lifelong Bioprosthetic heart valve: 3-6m Left ventricular thrombus: 3 months, repeat TTE to document resolution before stopping

Question 30

Why do pt with mechanical heart valves require lifelong warfarin therapy?

Answer 30

- Thrombogenecity of intravascular prosthetic material - Abnormal flow conditions imposed by mechanical valves, low flow and high shear stress can cause platelet activation, leading to valve thrombosis and embolic events - Also, INR target is higher 2.5-3.5 due to the thrombogenicity risk

Question 31

[REVERSAL] Warfarin reversal - INR <4.5 - INR 4.5-10 - INR >10

Answer 31

INR <4.5 - repeat INR, redose as needed INR 4.5-10 - withhold warfarin - repeat INR, redose as needed - DO NOT administer Vit K (if do: PO Vit K 1-2mg) INR >10 - withhold warfarin - PO Warfarin 2-5mg - Repeat INR and restart warfarin as necessary

Question 32

[REVERSAL] What are some independent predictors of slow normalization of INR? (INR remain elevated)

Answer 32

- Advanced age >=70yo - Decompensated HF - Acute malignancy - Low weekly warfarin dose

Question 33

[REVERSAL] Warfarin reversal - Major bleeding - Minor bleeding

Answer 33

Major bleeding - withhold warfarin - IV Vit K 5-10mg if INR >1.5 - Transfusion of platelets (FFP) - Supplement with PCC for life-threatening bleed - Repeat PT/INR/APTT 1h later Minor bleeding - withhold warfarin - assess bleeding risk vs thromboembolic risk - PO Vit K 1-2mg or IV 1mg

Question 34

[REVERSAL] Why is too much Vit K not desirable?

Answer 34

DO NOT DOSE 10mg - too much Vit K --> resistance/delayed anticoagulation for up to 3 weeks - those with high thrombogenic risk will not be able to prevent thrombus expansion

Question 35

[REVERSAL] Compare efficacy of oral vs IV Vit K

Answer 35

Similar effect at 24-48h

Question 36

[REVERSAL] Dabigatran

Answer 36

- withhold 1-2 days if renal function normal, non life-threatening bleed - dialysis (not likely effective) - idarucizumab (most effective if urgent reversal needed)

Question 37

[REVERSAL] Apixaban/Rivaroxaban

Answer 37

- withhold 1-2 days if renal function normal, non life-threatening bleed - Prothrombin complex concentrates PCC (not likely effective) - Andexanet alpha (most effective if urgent reversal needed, NA in SG)

Question 38

[REVERSAL] Warfarin

Answer 38

- withhold - Vit K - Fresh frozen plasma - transfuse platelets (require large volume) - PCC (most effective if urgent reversal needed)