Anticoagulant Management Janel Liane Cala PGY1 Pharmacy Resident - - PowerPoint PPT Presentation

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Anticoagulant Management Janel Liane Cala PGY1 Pharmacy Resident - - PowerPoint PPT Presentation

Jun 24, 2023 32 likes •428 views

Anticoagulant Management Janel Liane Cala PGY1 Pharmacy Resident Medical Center Hospital Objectives Review warfarin management Literature review for new oral anticoagulants (NOACs) in atrial fibrillation Clinical pearls for the

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Anticoagulant Management

Janel Liane Cala PGY1 Pharmacy Resident Medical Center Hospital

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Objectives

 Review warfarin management  Literature review for new oral anticoagulants

(NOACs) in atrial fibrillation

 Clinical pearls for the management of NOACs

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Bleeding Risk VS Stroke Risk

Total HAS- BLED Score % Bleeding 1 3.4% 2 4.1% 3 5.8% 4 8.9% 5 9.1% 6-8 Unable to predict due to small patient population Total CHADS2 Score % Stroke 1 2.8% 2 4.0% 3 5.9% 4 8.5% 5 and 6 > 8.5% Stroke history = automatic high risk

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Warfarin Management

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Warfarin Protein C and S (natural anticoagulant proteins)

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Factor Half-life (hour) VII 4-6 IX 21-30 X 27-48 II 42-72 Protein C* 8 Protein S* 60

  • Initial INR elevation = factor VII depletion
  • Initial procoagulant state during warfarin therapy
  • Full Antithrombotic effect= 5-7 days
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Pharmacokinetics

Absorption: 100% bioavailability Distribution: 98% protein bound

  • -- Unbound drug: active

Metabolism: CYP 2C9 CYP2C9 inhibitors: Amiodarone, Statin* (Simvastatin, Rosuvastatin), Fibrates AbX (Bactrim, Flagyl), Azoles Elimination: t ½ 20 – 60 hrs

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Factors Influence Warfarin Dose Requirement

 Goal INR  Interacting medications  Dietary vitamin K (must be relatively consistent)  Alcohol use  Underlying disease states (eg hepatic disease, hypoalbuminemia)  Age  Genetic factors

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Drug- Drug Interactions

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Dose Initiation Strategy

 Starting dose = an educated guest  Inpatient allows daily INR monitoring and dose

adjustment  utilize flexible dose initiation

 10 mg vs 5 mg initiation  Faster therapeutic INR attainment  Supratherapeutic INR, bleeding, and initial risk of

clotting

 Adjustment based on rate of INR change after the first 1

to 3 doses

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Monitoring

 Prothrombin time (PT) Measured by adding calcium and a tissue

thromboplastin to plasma

 INR = international normalized ratio

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INR Goals

CONDITION TARGET INR DVT/ PE Afib Mechanical Heart valves 2 - 3 2 - 3 2.5 – 3.5

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Frequency of INR Monitoring

INITIATION

Inpatient Daily until stable, then every 3-5 days After hospital discharge

  • STABLE
  • UNSTABLE

(at least weekly)

  • Within 5-7 days
  • Within 1-3 days

Stable* - at least 2 consecutive therapeutic INRs

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Frequency of INR Monitoring

LONG TERM MAINTENANCE

INR > 3.5 ; dose held today 7 days the latest Dosage change today Within 1-2 weeks Routine follow up stable, compliant q 4-6 weeks Routine follow up Unstable, non-compliant q 1 -2 weeks Consider other OAC

Stable* - at least 2 consecutive therapeutic INRs

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Dosage size

1mg (Pink) 2mg (Lavender) 2.5mg (Green) 3mg (Tan) 4mg (Blue)

5mg (Peach) 6mg (Teal) 7.5mg (Yellow) 10mg (White)

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Warfarin Reversal

 Fresh Frozen Plasma  Contains all coagulation factors  Act rapidly but short acting, should be used for

emergent reversal of elevated INRs

 Initial dose of FFP based on risk of bleeding Low to moderate risk – FFP 2 units  High risk or active bleeding – FFP 4 units  INR should be rechecked 1 hour after administration

  • f FFP.
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 Vitamin K (Phytonadione)  PO - safest and most reliable route reduce INR back to the therapeutic range within 24hr

without causing complete reversal or prolonged warfarin resistance

 IV - reserve for active bleeding quickly reverse INR can lead to extended warfarin resistance Vitamin K 10 mg / 100mL NS, infuse over 60 minutes

(anaphylactic rxn)

 SQ and IM should be avoided

Warfarin Reversal

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Kcentra (4F- PCC)

 Components: Factors II, VII, IX, X, Proteins C and S,

Antithrombin III, small amount of heparin and human albumin

 Contraindication: disseminated intravascular coagulation,

heparin-induced thrombocytopenia

 Dosed on amount of factor IX: 500 units/vial

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FFP KCentra Type specific ( must be ABO compatible) Not blood group specific; No need to thaw Dosed by Volume 8 vials Kcentra = 16 units (4L) FFP Dosed by Factor IX units 8 vials Kcentra = 16 units (4L) FFP Cheaper Correct INR faster Similar effect on INR after 24 hours Faster rate of administration $500u/vial

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Special Population and Warfarin

 Elderly (>75)  Pregnancy and lactation: stippled calcification and

nasal cartilage hypoplasia

 Alcoholism: alcohol inhibit warfarin metabolism.

 Binge drinking increases bleeding risk from elevated INR

and risk of falls.

 Renal disease and hemodialysis: lower dose may be

required due to decrease CYP2C9 activity

 Hypo-thyroidism decreases catabolism of clotting

factors  increase warfarin dose requirement

 Adjust warfarin dose when start or stop thyroid medication

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New Oral Anticoagulants

 Dabigatran (Pradaxa)  Rivaroxaban (Xarelto)  Epixaban (Eliquis)  Edoxaban (Savaysa)

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Rivaroxaban Apixaban Edoxaban Dabigatran

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NOACs Literature For Stroke Prevention in Patients with Atrial Fibrillation

(SEE HANDOUT)

  • Rivaroxaban- high risk patients (high CHADS2)
  • Apixaban- lower bleeding risk (equivalent to aspirin, better

than warfarin in both GIB and ICB)

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Case 1

MH is a 50 y/o male with PMH of chronic afib, heart failure, hypertension (SBP around 140 at home), stroke, and diabetes type 2. He is compliant with his warfarin regimen but want to switch to another agent because it is difficult for him to attend warfarin clinic on a regular basis. What is/are your approach to this situation?

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Case 1

 CHADS2 = 5 (> 8.5%)  HAS-BLED = 1 (3.4%)

↑CHADS2 ↓HASBLED

Rivaroxaban – once daily, study population has high average CHADS2 If home INR is available, can also arrange home INR and follow up via phone

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Case 2

 Similar patient as above, but age = 80, alcoholic, taking

ASA daily and hypertension is uncontrolled.

CHADS2 = 6 (> 8.5%) HAS-BLED = 5 (9.1%)

↑CHADS2 ↑HASBLED

Apixaban due to lower bleeding risk (equivalent to aspirin, better than warfarin in both GIB and ICB)

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Case 3

 70 y/o with chronic afib, uncontrolled HTN,

alcoholic, taking ASA daily for history of MI. CHADS2 = 1 (2.8%) HAS-BLED = 4 (8.9%)

↓CHADS2 ↑HASBLED

Anticoagulant risk may outweigh benefit in this patient

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NOAC >>> Warfarin

 Patient can afford NOACs or qualify

for patient assistance

 Difficult to monitor/control INR  Patient cannot come to clinic and

home monitoring is not available

 INR is unstable

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Warfarin >>> NOAC

  • 1. Relative medication non-compliance (forget a dose
  • ccasionally) due to short T1/2 of all NOACs
  • 2. Patient’s reference – would like to see INR to know that it is

working

  • 3. Indications that NOACs has not been studied (HIT, cancer

patients, etc.)

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NOAC Dosing

 No loading dose for atrial fibrillation  No bridging required (peak between 2-4 hours)  Renal dose adjustment

(see hand out)

 Apixaban 50% dose if patient meets at least 2/3 criteria:

age > 80 y/o, weight < 60kg, or Scr > 1.5

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Conversion to and from NOACs

 Heparin drip to NOACs:

 start NOACs at time of heparin drip discontinuation, may

wait 2-4 hours to initiate NOACs if concern about bleeding risk

 Lovenox to NOACs:

 give NOACs at the next scheduled Lovenox dose

 Warfarin to NOACs:  Wait until INR < 2 to initiate NOACs

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Drug to Drug Interaction

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Dosing Error

 Missed dose:  Do not double dose  Use half-way rule  Accidental Double dose:  Skip a dose for BID NOAC  For Daily dose: Continue the normal dosing

regimen without skipping the next daily dose

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Bleeding While Using a NOAC

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Elective Surgery

  • Minimal bleeding risk procedures: dental intervention, cataract or

glaucoma, endoscopy without surgery, superficial surgery

  • Low bleeding risk interventions: endoscopy with biopsy, prostate or

bladder biopsy, electrophysiological ablation, angiography, pacemaker

  • r ICD implantation
  • High risk surgeries: complex left sided ablation, spinal or epidural

anesthesia, lumbar puncture, thoracic surgery, abdominal surgery, major

  • rthopedic surgery, liver biopsy, kidney biopsy
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References

1)

Wittkowsky AK. Chapter 24: Warfarin (AHFS 20:12.04). Available at http://www.ashp.org/doclibrary/bookstore/p2548/sample- chapter-24.pdf. Accessed July 2015.

2)

Connolly SJ, Ezekowitz MD, Yusul S, et al. Dabigatran versus warfarin in patients wth atrial fibrillation. NEJM. 2009;361:1139-51.

3)

Granger CB, Alexander JH, Mcmurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. NEJM. 2011;11:981-992.

4)

Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. NEJM. 2011;364:806-17.

5)

Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in non-valvular atrial fibrillation. NEJM. 2011;365:883-91

6)

Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. NEJM. 2013;369:2093-104.

7)

Heidbuchel H, Verhamme P, Alings M, et al. European heart rhythm association practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15:625-651.