Traditional anticoagulants

Transcription

1 TEGH Family Practice Clinic Day April 4, 03 Use of Anticoagulants in 03: What s New (and What Isn t) Bill Geerts, MD, FRCPC Director, Thromboembolism Program, Sunnybrook HSC Professor of Medicine, University of Toronto National Lead, VTE Prevention, Safer Healthcare Now! Anticoagulants in 03 Unfractionated heparin Low molecular weight heparins: dalteparin (Fragmin ) enoxaparin (Lovenox ) tinzaparin (Innohep ) [fondaparinux (Arixtra )] Warfarin (Coumadin ) Novel Oral Anticoagulants (NOACs): Direct thrombin inhibitor - dabigatran (Pradaxa ) Direct FXa inhibitors - apixaban (Eliquis ) - rivaroxaban (Xarelto ) Traditional anticoagulants Traditional Anticoagulants Are all INDIRECT inhibitors of coagulation heparin (Coumadin ) Heparin AT LMWH AT X LMWH - dalteparin (Fragmin ) II - enoxaparin (Lovenox ) - tinzaparin (Innohep ) fibrinogen Fibrin Thrombus Low Molecular Weight Heparins dalteparin (Fragmin ), enoxaparin (Lovenox ), tinzaparin (Innohep ) Predictable drug effect - rapid onset, 4 hr coverage, no lab monitoring Flexible dosing: thrombosis vs bleeding risks 5 years experience Prophylaxis of choice for most hospital patients Only anticoagulant safe in pregnancy More effective than in cancer patients with VTE Using LMWH for Treatment of VTE Generally avoid if severe renal dysfunction Use pre-filled syringes (and round up) - e.g. for 74 kg use enoxaparin 0 mg not mg Use patient s actual body weight (no maximum) - e.g. for 50 kg use enoxaparin 50 mg BID Almost all patients self-inject - use CCAC only as a last resort BUT daily SC injection, renal clearance, cost

2 Treatment of DVT/PE: 3 options (INR.0-3.0) 5-7 d? 3 mosindefinite pregnancy, adenocarcinoma, failed therapeutic, high bleeding risk, short duration of treatment, patient preference LMWH SHOULD Replace LDH as thromboprophylaxis LMWH is:. More effective than LDH in some patients (stroke, cancer surgery, arthroplasty, trauma). Once daily vs BID/TID with LDH 3. Virtually eliminates risk of HIT 4. No greater bleeding (very uncommon) 5. Not more costly than heparin (or cheaper) 6. Eliminating LDH reduces options standardization 03 Thromboprophylaxis Summary Patient Group Options Duration Acute medical LMWH Discharge illness Surgery: general, gyne, thorac, urol LMWH Discharge Major orthopedics -THR, TKR rivaroxaban LMWH - Hip fracture surg LMWH High bleeding risk mechanical -6 weeks -6 weeks Until LMWH can start Warfarin (Coumadin ) 60 years experience Highly effective in a wide variety of thromboembolic conditions Only anticoagulant for mechanical heart valves Low bleeding risk for most patients Regular INRs required (undervalued by OHIP) Contraindicated in pregnancy Sometimes complex & requires obsessive Mx Effects of diet, physical activity, EtOH, other drugs, acute illness Using Warfarin Safely Monitor regularly (up to every 6 weeks if stable) Longitudinal records of doses, INRs by both MD and patient Avoid aspirin/plavix unless proven benefit Add PPI if must be on a platelet inhibitor Encourage generous vitamin K intake Optimal BP control Education, education, education Repeatedly reinforce compliance The novel/new oral anticoagulants (NOACs) apixaban (Eliquis ) dabigatran (Pradaxa ) rivaroxaban (Xarelto ) Consider anticoagulant clinic

3 New Oral Anticoagulants (NOACs) Are all DIRECT inhibitors of coagulation Approved in Canada Today apixaban dabigatran rivaroxaban Heparin LMWH fibrinogen X II Fibrin Thrombus Oral Xa inhibitors rivaroxaban (Xarelto) apixaban (Eliquis) Oral IIa inhibitors dabigatran (Pradaxa) Orthopedic prophylaxis Stroke prevention in AF VTE treatment Other indications No No No No No Med/surg thromboprophylaxis Mechanical heart valves Cancer, pregnancy # # # # ODB supported Warfarin vs New Oral Anticoagulants NOACs: Advantages Property NOACs Onset of action Slow (4-7 days) Rapid (-3 hrs) Dosing Variable (50-fold) Fixed Half-life Long (40 hrs) Medium (0-5 hrs) Lab monitoring Regularly Generally not Renal elimination No Yes (variable) Offset Slow (4-5 days) Shorter (- days) Antidote Yes, rapid Not proven, but Drug cost/month ~$5 (+ lab costs) ~$5 Property Rapid onset of action Less variability in anticoagulant effect No routine lab monitoring Relatively rapid offset of action Relatively inexpensive All of the above Advantages No need for IV/SC anticoag Fixed dose (or limited options) Convenient for patients, docs Simplifies pre-procedure Mx Generally affordable Potential for greater/longer use fewer thromboemboli Treatment of DVT/PE: 3 options NOACs in Atrial Fibrillation 3 (INR.0-3.0) 5-7 d? 3 mosindefinite pregnancy, adenocarcinoma, failed therapeutic, high bleeding risk, short duration of treatment, patient preference rivaroxaban (Xarelto ) 5 mg PO BID x 3 wks 0 mg daily Drug Dose Study No. dabigatran (Pradaxa ) rivaroxaban (Xarelto ) apixaban (Eliquis ) 0 mg BID or 50 mg BID RE-LY 8,3 0 mg BID ROCKET-AF 4,64 5 mg BID ARISTOTLE 8,0 All 3 NOACs appear to be at least as effective as All 3 NOACs appear to be at least as safe as All 3 NOACs were associated with reduced intracranial bleeding

4 Dabigatran Dosing in AF Contra-indications: Severe renal impairment (CrCL <30 ml/min) High risk for clinically significant bleeding Poorly compliant Concomitant treatment with strong P-glycoprotein inhibitors, e.g. ketoconazole. Dabigatran 50 mg BID Age <75, normal renal function, low bleeding risk Dabigatran 0 mg BID Age >75 CrCl Amiodarone Higher bleeding risk Rivaroxaban Dosing in AF Contra-indications: Severe renal impairment (CrCL <0 ml/min) High risk for clinically significant bleeding Poorly compliant Concomitant treatment with strong CYP 3A4 inducers (rifampin, St. John s Wort) Concomitant use of HIV protease inhibitors, ketoconazole Rivaroxaban 0 mg once daily Standard dose Rivaroxaban 5 mg once daily CrCl 0-30 High bleeding risk Switching Anticoagulants Warfarin to a NOAC Stop 3 days later, start NOAC [or get INR and start NOAC when INR <.0] NOAC to Warfarin Start, continue NOAC Stop NOAC when INR >.0 (N.B. timing of INR is critical before a dose of the NOAC) Laboratory Monitoring New OAC Poor correlation between standard coag tests and drug level Major variability in reagent/analyzer Timing of the test is critical 0 4 Assessment of reversal dabigatran rivaroxaban aptt PT (NOT INR) Monitoring of blood level (not yet!) Clinical Monitoring of Patients Taking NOACs ESSENTIAL Life-threatening diseases, life-threatening drugs Frequency depends on clinical stability Kidney function (at least yearly) Check and reinforce ADHERENCE Education Pre-Procedure Stopping of NOACs (apixaban, dabigatran, rivaroxaban) Renal Function (CrCL, ml/min) Half-life (hours) How far in advance of procedure should NOAC be stopped? days days <30 * More than 5 * Use of NOAC contra-indicated 4-5 days (check aptt or INR first)

5 Post-Procedure Restart of NOACs Ask yourself: Is it OK that the patient be fully anticoagulated hours after a dose? NOAC (stop - days preop if renal function normal) OR DAYS Restart NOAC at therapeutic doses* DVT prophylaxis with LMWH or prophylactic dose of NOAC Restart NOAC at therapeutic doses* Management of Bleeding on New Oral Anticoagulants. No specific antidotes for any. No human reversal of bleeding studies 3. No effect of vitamin K, plasma Rivaroxaban vs Dabigatran Feature Dabigatran Rivaroxaban Bioavailability <6% >80% Target Factor IIa Factor Xa Half life -7 hrs 6-3 hrs Drug Few (P-gp) Few (CYP 3A4) interactions Renal excretion 85% <35% Using NOACs Safely Careful selection of patients: good renal function, comorbidity, highly compliant, cost not an issue Know the drugs: pharmacology, findings of main clinical trials Avoid antiplatelet agents unless essential Education, education, education Periodic clinical monitoring Administration capsule BID tablet NOACs: Summary apixaban (Eliquis ), dabigatran (Pradaxa ), rivaroxaban (Xarelto ) Effective anticoagulants VTE prophylaxis in orthopedics, stroke prevention in AF, acute and longer-term VTE treatment Convenient - oral, rapid onset, no lab monitoring Lab - dabigatran (aptt), rivaroxaban (PT) Procedures - stop - days before (if renal function normal); be careful afterwards if increased bleeding risk