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TRG HARVARD MEDICAL SCHOOL TEACHING AFFILIATE Thrombosis Research - PDF document

Aug 13, 2023 •137 likes •301 views

BRIGHAM AND WOMENS HOSPITAL With All the New Drugs, This is How I Treat Acute DVT and Superficial Phlebitis Gregory Piazza, MD, MS Division of Cardiovascular Medicine Brigham and Womens Hospital April 20, 2018 TRG HARVARD MEDICAL

  1. BRIGHAM AND WOMEN’S HOSPITAL With All the New Drugs, This is How I Treat Acute DVT and Superficial Phlebitis Gregory Piazza, MD, MS Division of Cardiovascular Medicine Brigham and Women’s Hospital April 20, 2018 TRG HARVARD MEDICAL SCHOOL TEACHING AFFILIATE Thrombosis Research Group Disclosures • BMS- grant/research support • Daichii-Sankyo- grant/research support • BTG/EKOS- grant/research support • Janssen- grant/research support • Bayer- scientific advisory panel • Portola- scientific advisory panel TRG Thrombosis Research Group 1

  2. A 55-year-old woman with acute left leg swelling and pain • She recently underwent left knee arthroscopy for a partial medial meniscus tear. • She initially noted left knee swelling and pain but subsequently found the symptoms extended to her ankle. • She suspected it was typical for knee surgery and self-prescribed bed rest. TRG Thrombosis Research Group A 55-year-old woman with acute left leg swelling and pain • Her medical history was remarkable for obesity, type 2 diabetes, hypertension, hyperlipidemia, GERD, and obstructive sleep apnea. • Her medications included metformin, lisinopril, atorvastatin, omeprazole, and ibuprofen. • She was a 1-pack-per-day smoker and worked as a telemarketer. TRG Thrombosis Research Group 2

  3. A 55-year-old woman with acute left leg swelling and pain • On physical examination, she was afebrile with a blood pressure of 128/72 mmHg, heart rate of 77 bpm, and oxygen saturation of 99% on RA. • She had 2+ pitting edema from her left ankle to lower thigh and trace edema on the right. • Her left leg was slightly erythematous and tender to palpation. TRG Thrombosis Research Group A 55-year-old woman with acute left leg swelling and pain • Because of the high L FV suspicion for DVT, the patient was referred directly for venous ultrasound. • Venous ultrasound demonstrated left femoral and popliteal DVT. TRG Thrombosis Research Group 3

  4. Risk Stratification for Acute DVT Acute DVT Iliofemoral DVT Non‐iliofemoral DVT Consider catheter‐ Therapeutic assisted fibrinolysis anticoagulation and “Pharmacomechanical compression Therapy” stockings TRG Thrombosis Research Group Which Anticoagulant to Use in Acute DVT Unfractionated • Preferred in patients undergoing fibrinolysis, surgical or catheter Heparin thrombectomy, or IVC filter insertion Injectables or • Preferred in patients who require Direct Oral only anticoagulation Anticoagulants Direct Thrombin • Used in patients with suspected or confirmed heparin-induced Inhibitors thrombocytopenia (HIT) TRG Thrombosis Research Group 4

  5. Efficacy of DOACs for VTE Treatment: Meta-Analysis TRG van der Hulle T, et al. J Thromb Haemost. 2014;12:320 Thrombosis Research Group Safety of DOACs for VTE Treatment: Meta-Analysis Relative Risk TRG van der Hulle T, et al. J Thromb Haemost. 2014;12:320 Thrombosis Research Group 5

  6. Anticoagulation Strategy in Evolution LMWH/Warfarin UFH/Warfarin Overlapping Bridge Bridge LMWH to LMWH to Switching Dabigatran Edoxaban ( RE-COVER ) ( HOKUSAI-VTE ) Rivaroxaban (15 Apixaban (10 mg Oral mg 2x/d for 3 wks, 2x/d for 1 wk, then Monotherapy then 20 mg/d) 5 mg 2x/d) ( EINSTEIN ) ( AMPLIFY ) TRG Thrombosis Research Group Optimal Anticoagulation for Acute VTE: 2016 CHEST Guideline Update • In patients with DVT of the leg or PE and no cancer, as long-term (first 3 months) anticoagulant therapy, we suggest dabigatran, rivaroxaban, apixaban or edoxaban over VKA therapy (all Grade 2B). TRG Kearon C, et al. CHEST 2016 ;149:315 Thrombosis Research Group 6

  7. Contraindication Checklist for Home-Therapy of Acute DVT High Thrombotic Load • Massive DVT (iliofemoral) • Concomitant PE Increased Risk of Bleeding • Active bleeding or bleeding disorder (thrombocytopenia) • Advanced renal or liver disease Special Populations • Body weight <45 kg or >100 kg • Advanced elderly, pediatric patients, or pregnant women Symptom Control • Pain • Difficulty ambulating Concomitant Medical Disorder Requiring Admission TRG Thrombosis Research Group Beware May-Thurner Syndrome • Compression of the left common iliac vein by the right common iliac artery • Most common in young women • May present as a iliofemoral DVT or as chronic venous insufficiency TRG Fazel R, et al. N Engl J Med 2007; 357:53 Thrombosis Research Group 7

  8. Duration of Anticoagulation Acute DVT Unprovoked Provoked Indeterminate Cancer (idiopathic) Treat with 3-6 Assess individual Consider indefinite Consider prolonged months of risk of VTE duration anticoagulation as anticoagulation recurrence anticoagulation if long as cancer is low bleeding risk active Clinical risk factors: •Past/family history of VTE •Male gender •Thrombophilia •Chronic medical conditions (COPD, heart failure, inflammatory disorders) •Obesity •Chronic immobilization TRG Goldhaber SZ and Piazza G. Circulation 2011;123:664 Thrombosis Research Group Prevention of Recurrent Unprovoked VTE Study Intervention Recurrent VTE** PREVENT Warfarin, INR 1.5-2 ↓64% vs. placebo ELATE Warfarin, INR 2-3 ↓63% vs. INR 1.5-2 THRIVE III Ximelagatran vs. ↓84% placebo EINSTEIN- Rivaroxaban vs. ↓82% DVT placebo AMPLIFY-EXT Apixaban vs. ↓81% placebo RE-SONATE Dabigatran vs. ↓93% placebo RE-MEDY Dabigatran vs. Non-inferior warfarin, INR 2-3 **Regardless of thrombophilia status TRG Prandoni P, et al. Haematologica 2007;92:199 Goldhaber SZ and Piazza G. Circulation 2011;123:664 Thrombosis Research Group 8

  9. Extended Secondary Prevention for All VTE: EINSTEIN CHOICE TRG Weitz JI, et al. N Engl J Med 2017;376:1211 Thrombosis Research Group Selecting the Optimal Agent for Extended Therapy Increased Risk of Recurrent VTE after Standard Therapy No Cancer Cancer Non-High Bleeding High Bleeding Risk Risk and Willing to OR Not Willing to LMWH Continue Continue Monotherapy Anticoagulation Anticoagulation Low-Dose Aspirin DOAC OR Low- or OR Low-Dose Conventional- TRG Apixaban or Intensity Warfarin Rivaroxaban Thrombosis Research Group 9

  10. CLOT Trial: Dalteparin Monotherapy vs. Warfarin n = 676 52% TRG Lee AYY, et al. N Engl J Med 2003;349:146 Thrombosis Research Group DOACs in Cancer Patients with VTE: HOKUSAI VTE CANCER p = 0.09 p = 0.04 TRG Raskob GE, et al. N Engl J Med. 2018; 378:615 Thrombosis Research Group 10

  11. A 55-year-old woman with acute left proximal DVT provoked by surgery • The patient was discharged from the office on oral rivaroxaban 15 mg twice daily for 3 weeks and then 20 mg daily for a total of 6 months. • She was recommended to use compression stockings, 30-40 mmHg, thigh-high. • In follow-up, her symptoms resolved quickly and she had no further venous thromboembolic events. TRG Thrombosis Research Group A 62-year-old man with varicose veins and leg pain • The patient had long-standing varicose vein bilaterally but never thought to seek medical attention. • He noted a tender firm “cord-like” mass behind his left knee that felt warm to the touch. • His medical history was only significant for hypertension for which he took HCTZ. TRG Thrombosis Research Group 11

  12. A 62-year-old man with varicose veins and leg pain • On physical examination, the patient had a tender, erythematous cord extending superficially through his popliteal fossa. • He had numerous severe varicose veins bilaterally. • A venous ultrasound confirmed superficial vein thrombosis and no DVT. TRG Thrombosis Research Group Algorithm for Superficial Vein Thrombosis Superficial Vein Thrombosis Isolated With DVT or Cancer If concomitant DVT or cancer, treat with full-dose anticoagulation, otherwise… Assess Symptom Severity Severe Non-Severe If non-severe, treat conservatively with analgesia, otherwise… Severe Symptom Treatment Fondaparinux 2.5 mg QD Enoxaparin 1 mg/kg QD TRG Thrombosis Research Group 12

  13. CALISTO: Fondaparinux for Superficial Vein Thrombosis TRG Decousus H, et al. N Engl J Med. 2010;363:1222 Thrombosis Research Group CALISTO: Fondaparinux for Superficial Vein Thrombosis TRG Decousus H, et al. N Engl J Med. 2010;363:1222 Thrombosis Research Group 13

  14. Rivaroxaban vs. Fondaparinux for Superficial Vein Thrombosis: SURPRISE • Prospective, randomized, open-label, non-inferiority trial of superficial vein thrombosis to evaluate the efficacy and safety of 10 mg rivaroxaban daily compared to fondaparinux 2.5 mg once daily for 45 days. • A combined efficacy endpoint will evaluate thrombus progression, SVT recurrence, DVT, PE and death. • Safety end point will focus on major and clinically- relevant non-major bleeding. TRG Clinicaltrials.gov: NCT01499953 Thrombosis Research Group A 62-year-old man with varicose veins and superficial vein thrombosis • The patient was prescribed 45 days of low-dose fondaparinux 2.5 mg daily with excellent relief of symptoms and no recurrent events. • He was also prescribed compression stockings thigh- high, 30-40 mmHg but found them difficult to wear. • He was eventually referred for consideration of endovenous laser ablation given his episode of superficial vein thrombosis. TRG Thrombosis Research Group 14

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