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.
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|
|Acute DVT or PE||Parenteral anticoagulation (overlapping with a VKA) or rivaroxaban||1Ba|
|LMWH or fondaparinux suggested over:|
|PE with hypotension||Thrombolytic therapy (for patients who do not have high risk of bleeding)||2C|
|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.
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.
|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
|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
|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.|
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