Date post: | 14-Apr-2017 |
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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%
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