piazza how i treat dvt ucsf vasc symp 1.0 [read-only]
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TRGThrombosis Research Group
HARVARD MEDICAL SCHOOLTEACHING AFFILIATE
BRIGHAM ANDWOMEN’S HOSPITAL
With All the New Drugs, This is How I Treat Acute DVT and
Superficial Phlebitis
Gregory Piazza, MD, MSDivision of Cardiovascular Medicine
Brigham and Women’s HospitalApril 20, 2018
TRGThrombosis 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
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TRGThrombosis Research Group
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.
TRGThrombosis 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.
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TRGThrombosis Research Group
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.
TRGThrombosis Research Group
A 55-year-old woman with acute left leg swelling and pain
• Because of the high suspicion for DVT, the patient was referred directly for venous ultrasound.
• Venous ultrasound demonstrated left femoral and popliteal DVT.
L FV
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Risk Stratification for Acute DVT
Acute DVT
Iliofemoral DVT Non‐iliofemoral DVT
Consider catheter‐assisted fibrinolysis
“PharmacomechanicalTherapy”
Therapeutic anticoagulation and
compression stockings
TRGThrombosis Research Group
Which Anticoagulant to Use in Acute DVT
• Preferred in patients undergoing fibrinolysis, surgical or catheter thrombectomy, or IVC filter insertion
UnfractionatedHeparin
• Preferred in patients who require only anticoagulation
Injectables or Direct Oral
Anticoagulants
• Used in patients with suspected or confirmed heparin-induced thrombocytopenia (HIT)
Direct Thrombin Inhibitors
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Efficacy of DOACs for VTE Treatment: Meta-Analysis
van der Hulle T, et al. J Thromb Haemost. 2014;12:320
TRGThrombosis Research Group
Safety of DOACs for VTE Treatment: Meta-Analysis
van der Hulle T, et al. J Thromb Haemost. 2014;12:320
Relative Risk
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Anticoagulation Strategy in Evolution
Overlapping LMWH/WarfarinBridge
UFH/WarfarinBridge
SwitchingLMWH to
Dabigatran
(RE-COVER)
LMWH to Edoxaban
(HOKUSAI-VTE)
Oral Monotherapy
Rivaroxaban (15 mg 2x/d for 3 wks,
then 20 mg/d) (EINSTEIN)
Apixaban (10 mg 2x/d for 1 wk, then
5 mg 2x/d) (AMPLIFY)
TRGThrombosis 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).
Kearon C, et al. CHEST 2016 ;149:315
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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
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Beware May-ThurnerSyndrome• 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
Fazel R, et al. N Engl J Med 2007; 357:53
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Duration of Anticoagulation
Acute DVT
IndeterminateProvoked Unprovoked(idiopathic)
Treat with 3-6 months of
anticoagulation
Assess individual risk of VTE recurrence
Consider indefinite duration
anticoagulation if low bleeding risk
Clinical risk factors:•Past/family history of VTE•Male gender•Thrombophilia•Chronic medical conditions (COPD, heart failure, inflammatory disorders)•Obesity•Chronic immobilization
Cancer
Consider prolonged anticoagulation as long as cancer is
active
Goldhaber SZ and Piazza G. Circulation 2011;123:664
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Prevention of Recurrent Unprovoked VTE
Study Intervention RecurrentVTE**
PREVENT Warfarin, INR 1.5-2 vs. placebo
↓64%
ELATE Warfarin, INR 2-3vs. INR 1.5-2
↓63%
THRIVE III Ximelagatran vs. placebo
↓84%
EINSTEIN-DVT
Rivaroxaban vs. placebo
↓82%
AMPLIFY-EXT Apixaban vs. placebo
↓81%
RE-SONATE Dabigatran vs. placebo
↓93%
RE-MEDY Dabigatran vs. warfarin, INR 2-3
Non-inferior
**Regardless of thrombophilia status
Prandoni P, et al. Haematologica 2007;92:199Goldhaber SZ and Piazza G. Circulation 2011;123:664
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Extended Secondary Prevention for All VTE: EINSTEIN CHOICE
Weitz JI, et al. N Engl J Med 2017;376:1211
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Selecting the Optimal Agent for Extended Therapy
Increased Risk of Recurrent VTE after Standard Therapy
No Cancer
Non-High Bleeding Risk and Willing to
Continue Anticoagulation
DOAC OR Low- or Conventional-
Intensity Warfarin
High Bleeding Risk OR Not Willing to
Continue Anticoagulation
Low-Dose Aspirin OR Low-Dose Apixaban or Rivaroxaban
Cancer
LMWH Monotherapy
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n = 676
CLOT Trial: DalteparinMonotherapy vs. Warfarin
Lee AYY, et al. N Engl J Med 2003;349:146
52%
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DOACs in Cancer Patients with VTE: HOKUSAI VTE CANCER
p = 0.09
p = 0.04
Raskob GE, et al. N Engl J Med. 2018; 378:615
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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.
TRGThrombosis 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.
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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.
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Algorithm for Superficial Vein Thrombosis
Severe Symptom Treatment
Fondaparinux 2.5 mg QD Enoxaparin 1 mg/kg QD
Assess Symptom Severity
Severe Non-Severe
Superficial Vein Thrombosis
Isolated With DVT or CancerIf concomitant DVT or cancer, treat with full-dose anticoagulation, otherwise…
If non-severe, treat conservatively with analgesia, otherwise…
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CALISTO: Fondaparinux for Superficial Vein Thrombosis
Decousus H, et al. N Engl J Med. 2010;363:1222
TRGThrombosis Research Group
CALISTO: Fondaparinux for Superficial Vein Thrombosis
Decousus H, et al. N Engl J Med. 2010;363:1222
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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.
Clinicaltrials.gov: NCT01499953
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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.
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Take-Home Points
• The DOACs offer enhanced safety and similar efficacy compared with warfarin for acute treatment of DVT as well as long-term secondary prevention.
• The DOACs have facilitated home treatment of non-high risk acute DVT.
• The role of the DOACs in treatment of superficial vein thrombosis has yet to be defined.