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


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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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.


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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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.


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


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


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)


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


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


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


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%


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.


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.


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


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


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.

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Piazza How I Treat DVT UCSF Vasc Symp 1.0 [Read-Only]