ORAL ANTICOAGULANT

Dr. Md. Mashiul AlamPhase B ResidentUniversity cardiac centreBSMMU

20 Oct, 2015

Over view of Hemostasis

Over view of Hemostasis

Over view of Hemostasis

Platelet activation

Over view of Hemostasis

Coagulation Casecade

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

Warfarin

Pharmacokinetic dataRoute Oral

Bioavailability 100%

Protein binding 99.5%

Half Life 40 hours

Excretion Renal (92%)

Pregnancy category D

Indication

A. Therapeutic INR 2.5

1. Prevention and treatment of VTE2. Arterial embolism3. AF with stroke risk factor4. Post MI mobile mural thrombus5. Extensive anterior MI6. DCM7. Cardioversion8. Ischemic stroke in antiphospholipid syndrome9. MS and MR with AF

Indication cont’d…B. Therapeutic INR 3.5

1. Recurrent venous thrombosis whilst on warfarin

2. Mechanical prosthetic cardiac valves

Contraindication

Drug InteractionIncreased bleeding risk with warfarin:

1. Antiarrhythmics - amiodarone , propafenone2. Antibiotics - amoxicillin , cephalosporins , fluoroquinolones,

macrolides.3. Anticonvulsants - phenytoin ,sodium valproate4. Antidepressants -duloxetine ,venlafaxine, SSRI.5. Antifungals- fluconazole , itraconazole , ketoconazole.6. Antihyperlipidemics - Ezetimibe , fenofibrate ,Atorvastatin,

fluvastatin ,rosuvastatin

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

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

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%

http://en.wikipedia.org/wiki/File:Coumarin-induced_skin_necrosis.jpg

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.

What’s wrong with traditional anticoagulants

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

3 new oral anticoagulants (NOAC)

Debigatran

Rivaroxaban

Apixaban

Indication1. 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.

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

Prescribing an NOAC1. Detailed HistoryEXCLUSION Criteria: -Known hypersensitivity to NOAC preparation -Pregnant or breastfeeding -Stable warfarin therapy -Prosthetic heart valve -Recent stroke

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

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

4. Is patient on warfarin ?

Stop warfarin

Start a new oral anticoagulant when INR is

< 2

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.

Advantages over warfarin1. 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.

Thank you