The Role of the Newer Anticoagulants

Transcription

1 The Role of the Newer Anticoagulants WARFARIN = Coumadin DAGIBATRAN = Pradaxa RIVAROXABAN = Xarelto APIXABAN = Eliquis

2 INDICATION DABIGATRAN (Pradaxa) RIVAROXABAN (Xarelto) APIXABAN (Eliquis) Stroke prevention in non-valvular AF with at least one additional stroke risk factor 150 mg twice daily Reduce to 110 mg twice daily for people 75 years of age Consider 110 mg twice daily for people 20 mg daily Reduce to 15 mg daily for people with CrCl ml/min 5 mg twice daily Reduce to 2.5 mg twice daily for people with at least two of the following characteristics: CrCl ml/min Higher risk of major bleeding 80 years Body weight 60 kg Serum creatinine 133 micromol/l Duration Indefinite Indefinite Indefinite PBS listed NO NO NO Prevention of VTE in THR and TKR 220 mg once daily 150 mg once daily (CrCl ml/min) 10 mg daily 2.5 mg twice daily Duration THR = days TKR = 10 days THR = 35 days TKR = 14 days THR = days TKR = days PBS listed YES YES YES Treatment of DVT Not TGA approved 15 mg twice daily for 3 weeks then 20 mg daily[b,c] Not TGA approved PBS listed NO YES NO Prevention of recurrent DVT or PE Not TGA approved 20 mg daily[b,c] Not TGA approved PBS listed NO YES NO Abbreviations: CrCl = Creatinine clearance, DVT = deep vein thrombosis, PE = pulmonary embolism, THR = total hip replacement, TKR = total knee replacement, VTE = venous thromboembolism.

3 Based on the RE-LY study Dabigatran for preventing stroke in AF 1. Reduced incidence of stroke and systemic embolism 2. Reduced risk of ICH 3. Similar risk of major bleeding (which increases for all treatments with age and renal impairment) 4. Increased risk of GI bleed with 150mg dose only 5. Increased rate of dyspepsia 6. Increased risk of MI (not statistically significant) 7. No change to all-cause mortality Advantages of New Agents: 1. Reduction in risk of ICH 2. No need for monitoring 3. Less drug interactions than warfarin, but still need to be cautious with: a. PGP inhibitors such as amiodarone, verapamil and systemic ketoconazole which increase levels of dabigatran b. PGP inducers such as St John s Wort, carbamazepine and rifampicin c. A list of these meds can be found on PI for dabigatran on Medical Director Disadvantages of New Agents: 1. Lack of antidote. Not sure how significant a problem this is going to be. a. Life threatening bleeding b. Trauma c. Emergency surgery d. Treatment options include the usual such as blood transfusion, haemodialysis, activated charcoal, administration of prothrombin or recombinant VIIa 2. Contraindicated in severe renal impairment (CrCl < 30 ml/min) and severe liver impairment (Child-Pugh B or C) 3. No long term follow-up data 4. Uncertain compliance a. Have shorter half-life so increased risk of stroke (compared with warfarin) with missed doses b. Dabigatran does increase clotting time but not sure if that correlates well with clinical situation 5. Not been tested on people unsuited to warfarin 6. Contraindicated in severe renal impairment (usually Cr Cl < 30mL/min) 7. Cost approximately $36 vs $18

4 Which Newer Agent to Choose? Based on the RE-LY (dabigatran), ARISTOTLE (apixaban) and ROCKET-AF (rivaroxaban) trials 1. All 3 new agents have reduced risk of ICH but absolute risk reductions were small. 2. All 3 need caution with renal impairment but especially dabigatran. 3. Dabigatran and Apixaban were superior to warfarin in reducing stroke. Rivaroxaban was non-inferior to warfarin. All of these effects reduced if had good TTR 4. Dabigatran and rivaroxaban have increased risk of GI bleeding. 5. Apixaban also reduced overall mortality and reduced risk major bleeding 6. Rivaroxaban is only once daily dosing but increases risk of GI bleeding. It also only showed non-inferiority to warfarin whereas the others were superior to warfarin 7. If already taking warfarin and well controlled (TTR > 60%) then might be better to stay with the drug you know There are no head to head trials between the agents; only compared to warfarin Best stroke risk reduction: dabigatran and apixaban, warfarin if good TTR If high risk of GI bleeding, avoid rivaroxaban, dabigatran (high dose) If high risk of ICH: Any of the 3 newer agents can be used better than warfarin If mild/moderate renal impairment be careful with dabigatran especially If severe renal impairment best to stay with warfarin Dabigatran etexilate for preventing stroke and systemic embolism in atrial fibrillation. Medicine Today. 2013; 14(3): New oral anticoagulant drugs mechanisms of action. Australian Prescriber. 2010; 33: Apixaban approved: now which anticoagulant to use. Medscape. Jan 18, 2013 [May have industry bias] Good anticoagulant practice. NPS Medicine Wise. Feb 2013

5 The role of anticoagulation in non-valvular AF Risk of stroke Start anticoagulants based on assessment of risk of stroke using CHADS 2 or CHA 2 DS 2 -VASc: - If score = 0, patient low risk. Consider aspirin - If score 1, calculate risk using CHA 2 DS 2 -VASc; o If score = 0, not for any blood thinning treatment o If score =1, consider aspirin o If score >2, for anticoagulation - If score >2, then benefits from anticoagulation Risk of bleeding Identify risk factors for bleeding calculate risk of bleeding using HAS-BLED score: - If score >3, then patient considered to be higher risk - People patient is high risk, anticoagulation is NOT precluded but needs careful monitoring - Treat correctable risk factors for bleeding Online risk calcuators can be found on and can be saved as a favourite The benefits of warfarin (stroke reduction) outweigh the risks of ICH regardless of the HAS-BLED score (If CHADS > 1) The absolute risk of ICH is low with warfarin: 0.2% per year When using any anticoagulation, the risk of bleeding is also associated with: - Increasing age >75 years - Renal impairment < 30mL/min - The additional use of antiplatelet agents and/or NSAIDs Risk of falls In people with AF, those at higher risk of falls ALSO had a higher risk of stroke One study has shown benefit of warfarin in this double risk group, despite higher risk of ICH (1.9 Hazard Ratio) Age The risk of stroke increases with every decade of life The relative benefit of warfarin for preventing stroke does not change with age (whereas aspirin does become less beneficial with age > 75 yrs)