Warfarin and newer oral anticoagulants e.g. debigatran, rivaroxaban, apixaban were presented in cardiology morning session in Bangabandhu Sheikh Mujib Medical University.

1. ORAL
ANTICOAGULANT
Dr. Md. Mashiul Alam
Phase B Resident
University cardiac centre
BSMMU
20 Oct, 2015

2. Over view of Hemostasis

3. Over view of Hemostasis

4. Over view of Hemostasis
Platelet activation

6. Over view of Hemostasis
Coagulation
Casecade

8. Oral Anticogulants
 Old- Warfarin (Inhibit formation of Factor
Prothombin, VII, IX, X)
 New- 1. Debigatran (Direct Thrombin Inhibitor)
2. Rivaroxaban
3. Apixaban
Direct Factor Xa
Inhibitor

9. Warfarin

11. Pharmacokinetic data
Route Oral
Bioavailability 100%
Protein binding 99.5%
Half Life 40 hours
Excretion Renal (92%)
Pregnancy category D

12. Indication
A. Therapeutic INR 2.5
1. Prevention and treatment of VTE
2. Arterial embolism
3. AF with stroke risk factor
4. Post MI mobile mural thrombus
5. Extensive anterior MI
6. DCM
7. Cardioversion
8. Ischemic stroke in antiphospholipid syndrome
9. MS and MR with AF

13. Indication cont’d…
B. Therapeutic INR 3.5
1. Recurrent venous thrombosis whilst on
warfarin
2. Mechanical prosthetic cardiac valves

14. Contraindication

15. Drug Interaction
Increased bleeding risk with
warfarin:
1. Antiarrhythmics - amiodarone , propafenone
2. Antibiotics - amoxicillin , cephalosporins ,
fluoroquinolones, macrolides.
3. Anticonvulsants - phenytoin ,sodium valproate
4. Antidepressants -duloxetine ,venlafaxine, SSRI.
5. Antifungals- fluconazole , itraconazole , ketoconazole.
6. Antihyperlipidemics - Ezetimibe , fenofibrate ,Atorvastatin,
fluvastatin ,rosuvastatin

16. Drug interaction
Decreased therapeutic effect of warfarin:
1. Antibiotics - Rifampin
2. Antidepressants- Trazodone
3. Antiepileptics - Carbamazepine ,
phenobarbitone ,phenytoin.

17. Food to avoid while on Warfarin
 Vegetables that include
cauliflower, kale, Brussels
sprouts, asparagus, spinach,
alfalfa, turnip greens, mustard
greens and collard greens
 Beverages such as herbal teas
(green tea) and coffee.
 Vegetable oils that include
soybean, olive.
 Peas and green onions
 Dairy products such as yogurt

18. Complications
 Hemorrhage- 2.7% (major- 1.1%-8.1%)
 Warfarin Embryopathy -5% -30%
 Warfarin necrosis- 0.02%
 Osteoporosis- 0.1%
 Purple toe syndrome-0.01%

22. Some facts about warfarin
 It is safe to breastfeed during warfarin therapy
as there is minimal excretion into breast milk.
 Warfarin reduces the scarring on the liver
caused by Hepatitis C.
 Dosage adjustments are generally not
necessary in renal impariment. Patients with
CKD required on average 25% reduction of
warfarin dose.

23. What’s wrong with traditional
anticoagulants

24. Traditional anticoagulants have 2 major
limitations:
1. Narrow therapeutic window of adequate
anticoagulation without bleeding
2. Highly variable dose-response, requiring
monitoring by lab testing

25. 3 new oral anticoagulants
(NOAC)
Debigatran
Rivaroxaba
n

26. Apixaban

27. Indication
1. Prevention of venous thromboembolism in a
patient undergoing total hip or knee replacement
2. Prevention of stroke or systemic embolism in
patients who have non-valvular atrial fibrillation
and has one or more risk factors for developing
stroke or systemic embolism
3. Rivaroxaban for the prevention of recurrent
venous thromboembolism and for the treatment
of deep vein thrombosis and pulmonary
embolism.

28. Contraindication
 Known hypersensitivity to ingredients of NOAC
 Clinically significant active bleeding
 Renal impairment GFR <30ml/min
 Hepatic disease. (Child Pugh – C)
 Recent high risk bleeding lesion (eg. ICH < 6
months)
 Pregnancy or breast feeding
 Recent stroke, surgery, GI bleed or ulcer
 Recent fibrinolytic therapy <10days
 Concomitant warfarin therapy

29. Prescribing an NOAC
1. Detailed History
EXCLUSION Criteria:
-Known hypersensitivity to NOAC preparation
-Pregnant or breastfeeding
-Stable warfarin therapy
-Prosthetic heart valve
-Recent stroke

30. 3. Assess bleeding risk
-Disorder of haemostasis
-Recent surgery (≤ 1 month ago)
-GI bleed ≤ 12 months ago
-Ulcer ≤ 30 days ago
-Fibrinolytic treatment last 10 days
-Dual antiplatelet therapy

31. 3. Lab tests – FBC, U&E, LFTs
Contraindications:
-Poor renal function (CrCl ≤ 30 mL/ min,
apixaban: ≤ 15 mL/min)
-Liver disease (e.g. ALT > 3x upper limit of
normal)
-Hb ≤ 10 g/dL

32. 4. Is patient on warfarin ?
Stop warfarin
Start a new oral anticoagulant when INR is < 2

33. Limitations of NOAC
 Cost is high though cost effective than warfarin.
(Debigatran vs warfarin -450$/ month vs 30$/ month)
 No antidote available right now though can be removed by
dialysis. New antidote is under phase II trial.
 Possibly increased risk of MI
 major GI bleeding may be higher.
 Carefully selected patients for Phase III trial are not
representative of real world data. More Phase IV trials are
needed until then it should be used in selected patients.

34. Advantages over warfarin
1. Stable and predictable pharmacokinetics
2. No interaction with diet and alcohol
3. No significant drug interaction apart from
ketoconazole, amiodarone, verapamil
4. No monitoring required
5. Intracerebral and life threatening bleeding rates
are lower than warfarin.

36. Thank you