Essence of this Article

Prompt diagnosis and treatment of deep vein thrombosis (DVT) is essential to decrease both the risk of recurrence and a potentially fatal pulmonary embolism (PE). Traditionally, initial treatment of DVT and PE begins with a parenteral anticoagulant, transitioning to longer-term Vitamin K antagonist (VKA) therapy. Another option is the direct Factor Xa inhibitor rivaroxaban, an oral anticoagulant. This single-drug approach removes the need for overlapping administration of heparin and a VKA, which can be complex owing to the requirement for coagulation monitoring and dose-adjustment of the VKA. The use of compression stockings is an important adjunct to pharmacological treatment in patients with DVT. Other venous thromboembolism (VTE) treatment approaches may include: surgery; catheter-guided thrombectomy; or thrombolytic therapy.

Venous thromboembolism is a serious public health concern

The most effective and economical approach to decreasing the burden of VTE is to prevent the development of DVT and PE in patients at high risk.

Learn more about preventing VTE

However, DVT and PE continue to be a common problem in hospitalized patients, and in some cases this may be attributable to underutilization of thromboprophylaxis. DVT and PE also develop spontaneously in non­hospitalized patients. Prompt diagnosis and treatment of DVT are essential to decrease the risk of recurrence and also a potentially fatal PE.

The goals of DVT and PE treatment are:

  • Prevention of thrombus growth
  • Symptomatic relief
  • Prevention of DVT and PE recurrence

Treatment of DVT and PE with anticoagulants

Traditionally, initial treatment of DVT and PE begins with a parenteral anticoagulant, transitioning to longer-term vitamin K antagonist (VKA) therapy, often with warfarin. Because VKAs have a delayed onset of action, the transition requires close monitoring of the international normalized ratio (INR), which should be in the therapeutic range (INR 2.0–3.0) before discontinuation of the parenteral agent.156

ACCP guidelines for the treatment of DVT and PE with anticoagulants157

  ACCP recommendation Grade of recommendation
Initial anticoagulation
Acute DVT or PE Parenteral anticoagulation (overlapping with a VKA) or rivaroxaban 1Ba
  LMWH or fondaparinux suggested over:  
  i.v. UFH 2C
  s.c. UFH 2B
PE with hypotension Thrombolytic therapy (for patients who do not have high risk of bleeding) 2C
Long-term therapy
DVT or PE without cancer VKA suggested over LMWH 2C
  LMWH suggested over dabigatran or rivaroxaban 2Ca
DVT or PE with cancer LMWH suggested over VKA 2B
  VKA suggested over dabigatran or rivaroxaban 2Ba
Duration of anticoagulant therapy
Proximal DVT or PE 3 months recommended over shorter duration 1B
First proximal DVT or PE provoked by surgery or a non-surgical transient risk factor 3 months 1B (2B if provoked by a non­surgical risk factor and a low/moderate risk of bleeding)
Unprovoked DVT or PE Extended therapy if risk of bleeding is low/moderate 2B
  3 months if risk of bleeding is high 1B
DVT or PE associated with active cancer Extended therapy recommended over 3 months therapy 1B (2B if risk of bleeding is high)
aNo Grade of recommendation available for rivaroxaban or dabigatran.
ACCP, American College of Chest Physicians; DVT, deep vein thrombosis; LMWH, low molecular weight heparin; PE, pulmonary embolism; UFH, unfractionated heparin; VKA, vitamin K antagonist.

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The direct Factor Xa inhibitor rivaroxaban is the first novel oral anticoagulant approved in the EU for the treatment of DVT, PE and prevention of recurrent DVT and PE in adult patients.158 Rivaroxaban can be used for the initial and longer-term treatment of DVT, PE and recurrent VTE. This single-drug approach removes the need for overlapping administration of heparin and a VKA, which can be complex owing to the requirement for coagulation monitoring and dose-adjustment of the VKA.

EU marketing approval for rivaroxaban was received following a review of data from the randomized, controlled phase III EINSTEIN clinical trial programme.

Drug Target Dose/regimen Supporting data
UFH Factor Xa and thrombin (indirect via AT) Weight-adjusted s.c. bolus dose followed by i.v. infusion; overlapping with a VKA for at least 5 days and until INR >2.0 for 2 consecutive days  
LMWH Factor Xa and thrombin (indirect via AT) Weight-adjusted s.c. regimen; overlapping with a VKA for at least 5 days and until INR >2.0 for 2 consecutive days COLUMBUS159
Fondaparinux Factor Xa (indirect via AT) Weight-adjusted s.c. regimen (standard dose 7.5 mg) od; overlapping with a VKA for at least 5 days and until INR >2.0 for 2 consecutive days160 MATISSE DVT160

MATISSE PE161
VKA Vitamin K (inhibits synthesis of Factors II, VII, IX and X) Oral, commenced in parallel with initial parenteral agent, which is then discontinued once INR is in the range 2.0–3.0146

For warfarin, typical induction 5 mg (for older, frailer patients) or 10 mg (for younger, healthier patients) od for 2 days, followed by adjusted-doses to maintain a target INR of 2.5 (range, 2.0–3.0)

Treatment continues for 3–12 months depending on risk factors, or longer if risk factors for recurrence persist
Cochrane Database Systematic Review162
Rivaroxaban (Treatment of DVT and prevention of recurrent VTE only Factor Xa (direct) Oral, 15 mg bid for 3 weeks then 20 mg od

Oral 15 mg bid for 3 weeks then 20 mg od for patients with moderate (CrCl 30–49 ml/min) or severe (CrCl 15–29 ml/min) renal impairment158

A reduction of the dose from 20 mg od to 15 mg od should be considered if the patient’s assessed risk of bleeding outweighs the risk of recurrent DVT and PE
EINSTEIN DVT163

EINSTEIN PE164

EINSTEIN EXT163
AT, antithrombin; bid, twice daily; CI, confidence interval; DVT, deep vein thrombosis; INR, international normalized ratio; LMWH, low molecular weight heparin; od, once daily; PE, pulmonary embolism; s.c., subcutaneous; UFH, unfractionated heparin; VKA, vitamin K antagonist.

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Other treatment approaches for DVT and PE

The use of compression stockings is an important adjunct to pharmacological treatment in patients with DVT. Other VTE treatment approaches may include surgery, catheter-guided thrombectomy or thrombolytic therapy.157 Thrombolytic agents are given by regional catheter-directed infusion or systemically, and they dissolve fresh thrombi and restore venous flow more rapidly than anticoagulants.156

Thrombolytic therapy is associated with an increased risk of bleeding (major bleeding occurs in 5–10% of patients).165 For this reason, it is generally reserved for patients with a DVT that threatens the viability of a limb,156 or for PE associated with cardiogenic shock or hypotension.144