IC5 SPAF Flashcards
Explain how AFib can result in stroke
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
Why are DOACs recommended over VKAs in SPAF?
- 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
When is warfarin still required?
- Valvular AF (Mechanical/Prosthetic heart valves, mod-severe mitral stenosis)
- Left ventricular thrombus
- APS
In what situation might Warfarin be favoured over DOAC?
- 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
Ischemic stroke risk scoring: CHA2DS2-VASc score
- 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)
Based on CHA2DS2-VASc score, when to initiate OAC for SPAF?
Score of >=2 in men, and >= 3 in women
HASBLED score to estimate bleeding risk
- 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)
How is HASBLED score used to determine use of anticoagulants in SPAF?
- 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
ABC pathway of SPAF
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
What might be used for SPAF if pt has major bleeding, and cannot use OAC
Left atrial appendage (LAA) occlusion
- Watchman device implanted to catch clot and prevent clot from entering circulation
[SPAF dosing + renal adjustments]
- Apixaban
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
[SPAF dosing + renal adjustments]
- Rivaroxaban
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
[SPAF dosing + renal adjustments]
- Edoxaban
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
[SPAF dosing + renal adjustments]
- Dabigatran (most renally cleared)
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)
Evidence of OAC use for SPAF in elderly
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
Which two DOACs are preferred in elderly?
Apixaban
Edoxaban
Evidence of OAC use for SPAF in low body weight
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
VKA in SPAF
- What are the targets?
INR 2-3 (only if mechanical aortic heart valve: 2.5-3.5)
TTR: 70%
[SPAF structure follow up]
Baseline monitoring parameters before OAC initiation
- Blood test (include Hb, renal/liver function, coagulation panel)
[SPAF structure follow up]
Interval for follow-up (blood sampling) after initiation of OAC
Blood sampling: Hb/FBC, renal, liver function
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)
[SPAF structure follow up]
Structured follow-up after initiation of OAC
- 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
Switching from DOAC to Warfarin
- INR <2
- INR >=2
- 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
Switching Warfarin to DOAC
- INR <2
- INR 2-2.5
- INR 2.5-3
- INR >=3
- 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
[Bleeding while using NOAC]
- what should be determined first?
- NOAC dose, time of last intake
- Co-medications
- Blood sampling - determine CrCl, hepatic function, WBC
- Rapid coagulation assessment
- Plasma drug levels (if available)
[Bleeding while using NOAC]
Management of MILD bleeding in pt taking DOAC
- 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
[Bleeding while using NOAC]
Management of NON-LIFE THREATENING MAJOR bleeding in pt taking DOAC
- 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)
[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.
- 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)
DOAC - unplanned invasive procedure
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
Duration of Warfarin in different indications
- DVT, PE, thrombus
- SPAF
- Valvular heart disease
- Mechanical heart valve
- Bioprosthetic heart valve
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
Why do pt with mechanical heart valves require lifelong warfarin therapy?
- 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
[REVERSAL]
Warfarin reversal
- INR <4.5
- INR 4.5-10
- INR >10
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
[REVERSAL]
What are some independent predictors of slow normalization of INR? (INR remain elevated)
- Advanced age >=70yo
- Decompensated HF
- Acute malignancy
- Low weekly warfarin dose
[REVERSAL]
Warfarin reversal
- Major bleeding
- Minor bleeding
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
[REVERSAL]
Why is too much Vit K not desirable?
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
[REVERSAL]
Compare efficacy of oral vs IV Vit K
Similar effect at 24-48h
[REVERSAL]
Dabigatran
- withhold 1-2 days if renal function normal, non life-threatening bleed
- dialysis (not likely effective)
- idarucizumab (most effective if urgent reversal needed)
[REVERSAL]
Apixaban/Rivaroxaban
- 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)
[REVERSAL]
Warfarin
- withhold
- Vit K
- Fresh frozen plasma - transfuse platelets (require large volume)
- PCC (most effective if urgent reversal needed)
