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AT10 Presentation
- 1. Antithrombotic Therapy for VTE Disease: 10th edition ALLYSON CORD, PHARMD CANDIDATE 2016
- 2. VENOUS THROMBOEMBOLISM DVT: blood clot formed in a vein that partially or completely blocks circulation PE: obstruction of the pulmonary artery or one of its branches by material that originated elsewhere in the body (thrombus) Causes: Virchow’s triad Alterations in blood flow (stasis) Vascular endothelial injury Hypercoagulable state Malignancy, Factor V Leiden mutation, protein S deficiency, protein C deficiency, antiphospholipid antibodies, IBD, pregnancy
- 3. Clinical Presentation DVT Unilateral extremity swelling, discoloration, pain, tenderness PE SOB Chest pain Tachypnea Tachycardia Hypotension (hemodynamically unstable or massive PE) SBP <90 mmHg for a period >15 minutes, or requires vasopressors or inotropic support http://www.dvtforum.com/index.asp?action=start
- 4. Diagnosis D-dimer Degradation product of fibrin clot Sensitive but not specific Radiographic contrast studies – venography, pulmonary angiography Gold standard Most accurate and reliable Expensive and invasive Ultrasound Less invasive
- 5. Etiology Classification Provoked Transient/reversible Surgery, pregnancy, immobilization Persistent Malignancy, indefinite hypercoagulable state Unprovoked Unidentifiable cause
- 6. Anticoagulation Therapy for VTE Disease CHEST GUIDELINE, 10TH ED
- 7. Choice of Anticoagulant DVT/PE and no cancer (Grade 2B) Recommend dabigatran, rivaroxaban, apixaban, or edoxaban over VKA therapy, and VKA therapy over LMWH DVT/PE and cancer (Grade 2C) Recommend LMWH over dabigatran, rivaroxaban, apixaban, edoxaban, or VKA therapy No need to change the choice of anticoagulant after the first 3 months of therapy (Grade 2C) NOAC > VKA > LMWH Cancer = LMWH
- 8. NOAC evidence 4 new RCTs and extensive clinical experience Risk reduction similar between NOACs and VKA Risk reduction greater with LMWH than VKA in patients with cancer Risk reduction seems to be similar between all NOACs No direct comparison Risk of bleeding less with NOACs than VKA GI bleeding may be higher, though Risk may be less with apixaban Risk of fatal bleeding similar between VKA and NOACs Conclusion, less bleeding and greater convenience with NOACs
- 9. Parenteral Anticoagulation Dosing UFH 80 U/kg IV bolus followed by 18 U/kg/hr 5000U IV bolus followed by 1000 U/hr Enoxaparin 1 mg/kg SQ Q12H 1.5 mg/kg SQ QD CrCl < 30: 1 mg/kg SQ Q24H Fondaparinux < 50kg: 5mg SQ QD 50-100kg: 7.5mg SQ QD > 100kg: 10mg SQ QD Tinzaparin 175 U/kg SQ QD CrCl < 30: use with caution Nadroparin 171 U/kg SQ QD CrCl 30-50: reduce dose by 25-33% CrCl < 30: CI Dalteparin – off-label
- 10. Oral Anticoagulation Therapy Vitamin K Antagonist - warfarin Started on day 1 or 2 of parenteral anticoagulation Maintain overlap for at least 5 days and INR therapeutic for 48 hours INR goal = 2-3 Many diet, drug, and disease interactions OR NOAC – rivaroxaban, apixaban, edoxaban, dabigatran Preferred VTE treatment
- 11. Rivaroxaban (Xarelto) Dosing DVT/PE treatment: 15mg BID x 21 days followed by 20mg QD Take with food Extremes in weight do not influence Does not require parenteral anticoagulation prior to initiation Reduction in risk of recurrence: 20mg QD Renal and hepatic impairment CrCl < 30: avoid use Moderate-severe hepatic impairment: avoid use
- 12. Rivaroxaban (Xarelto) Characteristics ADR Bleeding/thrombosis Spinal/epidural hematoma DDI CYP 3A4 (major) CYP 2J2 (minor) P-gp Pregnancy C D/c 24 hours prior to surgery CrCl < 50: consider d/c 3-5 days prior
- 13. Apixaban (Eliquis) Dosing DVT treatment: 10mg BID x 7 days followed by 5mg BID Does not require parenteral anticoagulation prior to initiation Reduction in risk of recurrence: 2.5mg BID after at least 6 months of DVT treatment Renal impairment CrCl < 30: use with caution Under nonvalvular atrial fibrillation ≥ 80 yoa AND weighs ≤ 60kg or SCR ≥ 1.5 reduce dose by 50% Hepatic impairment Moderate: use with caution Severe: not recommended
- 14. Apixaban (Eliquis) Characteristics ADR Bleeding/thrombosis Spinal/epidural hematoma DDI CYP 3A4 (major) Reduce dose by 50% CYP 1A2, 2C19, 2C8, 2C9 (minor) P-gp Pregnancy B D/c 24-48 hours prior to surgery
- 15. Edoxaban (Savaysa) Dosing DVT/PE treatment: 60mg QD Requires 5-10 days of parenteral anticoagulation prior to initiation Weight dose adjustment ≤ 60kg: reduce dose by 50% Renal impairment CrCl > 95: avoid CrCl 15-50: reduce dose by 50% CrCl < 15: avoid Hepatic impairment Moderate-severe: avoid
- 16. Edoxaban (Savaysa) Characteristics ADR Bleeding/thrombosis Spinal/epidural hematoma Abnormal LFTs DDI with specific P-gp inhibitors Verapamil, quinidine, macrolides, oral itraconazole, oral ketoconazole Reduce dose by 50% Pregnancy C D/c 24 hours prior to surgery
- 17. Edoxaban (Savaysa) CrCl > 95 CrCl 95-51 CrCl 50-15 CrCl < 15 > 61kg Avoid 60mg 30mg Avoid P-gp Avoid 30mg 15mg Avoid ≤ 61kg Avoid 30mg 15mg Avoid P-gp Avoid 15mg avoid Avoid
- 18. Dabigatran (Pradaxa) Dosing DVT/PE treatment/prevention: 150mg BID After 5-10 days of parenteral anticoagulation Take with full glass of water Dispense in original container Discard 4 months after opening Renal CrCl < 50 and concomitant P-gp: 75mg BID CrCl ≤ 30: dose not provided Non-valvular a fib with CrCl 15-30: 75mg BID If with P-gp, avoid CrCl < 15: not studied, CI per CHEST Hepatic Severe impairment: avoid
- 19. Dabigatran (Pradaxa) Characteristics ADR Bleeding/thrombosis Spinal/epidural hematoma GI upset DDI P-gp inhibitor Pregnancy C d/c 1-2 days or 3-5 days (CrCl < 50) before surgery Reversal Idarucizumab (Praxbind) 5g dose (2 2.5g vials) Give within 15 mins Dialyzable
- 20. NOAC Comparison NOAC Parenteral needed Weight adj DDI Reversal Unique Rivaroxaban No No 3A4, P-gp No Take with food Apixaban No ~ No 3A4, P-gp No Pregnancy B Edoxaban Yes Yes P-gp No CrCl > 95: avoid Dabigatran Yes No P-gp Praxbind, dialyzable GI upset
- 21. Thrombophilia Recommended treatment: UFH or LMWH followed by VKA Sufficient data not available regarding safety and efficacy of NOACs in patients with thrombophilia RAPS: rivaroxaban vs enoxaparin with warfarin in APS Antithrombin deficiency Heparin resistance – need larger doses Not as much AT for heparin to reduce Protein C deficiency Warfarin-induced skin necrosis
- 22. Duration of Anticoagulant Therapy Active treatment = 3-6 months Secondary prophylaxis Primary risk factor – provoked vs unprovoked Provoked by transient/reversible risk factor = lowest risk of recurrence 3 months Unprovoked/unidentifiable = moderately high risk of recurrence Base duration of therapy on secondary risk factors and bleeding risk Provoked by progressive/persistent factor = highest risk of recurrence Indefinite therapy Secondary risk factors – location and history Second episode = indefinite therapy UE or isolated distal (unprovoked or transient provoked) = 3 months Indefinite therapy only recommend in low-moderate bleeding risk!
- 23. Management of Recurrent VTE on Anticoagulant Therapy Unusual occurrence so reevaluate: Diagnosis Compliance Underlying malignancy If occurs while on therapeutic VKA or NOAC therapy, suggest switching to LMWH therapy at least temporarily At least 1 month If occurs while on long-term LMWH, suggest increasing dose by 1/4 -1/3
- 24. Aspirin for Extended Treatment of VTE “In patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy and do not have a contraindication to aspirin, we suggest aspirin over no aspirin to prevent recurrent VTE (Grade 2B).” Not a reasonable alternative 80% reduction vs 30% Additional indications
- 25. Systemic Thrombolytic Therapy for PE Suggested indications for thrombolytic use PE associated with hypotension Acute PE that deteriorates after starting anticoagulant therapy Suggest using a peripheral vein over catheter-directed thrombolysis Only use if low risk of bleeding! If massive PE with high bleeding risk, failed systemic thrombolysis, or shock, suggest catheter-assisted thrombus removal Only if appropriate expertise and resources available
- 26. Compression Stockings to Prevent PTS “In patients with acute DVT of the leg, we suggest not using compression stockings routinely to prevent PTS (Grade 2B)” Post-thrombotic syndrome: chronic complication of DVT resulting in chronic venous insufficiency Larger RCT showed no benefit A trial of compression stockings may be tried for s/s associated with PTS
- 27. Whether to Anticoagulate Subsegmental PE Subsegmental PE: no involvement of the more proximal pulmonary arteries Low risk of recurrent VTE clinical surveillance As long as no DVT also present More likely a false positive or arose from a small DVT High risk of recurrent VTE anticoagulation Evaluate bleeding risk
- 28. Treatment of Acute PE Out of the Hospital “In patients with low-risk PE and whose home circumstances are adequate, we suggest treatment at home or early discharge over standard discharge (Grade 2B).” Standard discharge: after first 5 days of treatment
- 29. Summary Non-Cancer: NOAC > VKA > LMWH Cancer: LMWH Recurrent: Switch to LMWH or increase LMWH dose ASA: consider upon anticoagulant d/c Thrombolytic: only in massive or deteriorating PE Compression stockings: do not routinely use Subsegmental: base therapy on risk
- 30. References DiPiro JT, Talbert RL, Yee GC, et. al. Pharmacotherapy: A Pathophysiologic Approach, Ninth Edition. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 10th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2016;149(2):315-352. Kearon C, Akl EA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood 2014; 123(12):1794-1801. Lexi-Drugs. Lexicomp Online. Wolters Kluwer Health, Inc. Hudson, OH. Available at: http://online.lexi.com. Accessed February 4, 2016. Bauer KA. Management of inherited thrombophilia. UpToDate. Wolters Kluwer Health, Inc. Hudson, OH. Available at: http://www,uptodate.com/contents/management-of-inherited-thrombophilia
- 31. Questions?
Editor's Notes
- D-dimer elevated in acute thrombosis
- Recommended for cancer treatment and required prior to starting some of the oral anticoagulants
- Fairly easy dosing
- Complicated dosing
- No change but more evidence. Cancer – continue for 3 months after cancer-free
- Addition
- New addition: Asa therapy may be beneficial in patients who d/c anticoagulant therapy if no Cis. But better than nothing. Use of aspirin should also be reevaluated when patients stop anticoagulant therapy because aspirin may have been stopped when anticoagulants were started.
- Revision, more clarification Deterioration – tachycardia, BP decrease, worsening gas exchange, shock, cardiac markers More evidence supporting systemic than CDT
- Revised
- New addition
- Revision