Treatment of acute VTE

Initial treatment with anticoagulants

After diagnosis, the treatment objectives of initial therapy are prevention of DVT extension or prevention of pulmonary embolism (PE) occurrence or recurrence, and relief of acute symptoms while averting haemodynamic collapse or death [34]. These objectives are compelling and explain the practice of prescribing therapy if diagnostic testing for VTE is delayed.

Initial VTE treatment requires therapeutic dosages of anticoagulants. With the recent licensing of non-vitamin K antagonist oral anticoagulants (NOACs) for the treatment of VTE, there are now three different approaches to the initial treatment of VTE.

Two-drug approach of VKA with bridging heparin

Patients are initiated on a short course of parenteral heparin (usually low molecular weight heparin (LMWH), or alternatively unfractionated heparin (UFH) or fondaparinux) overlapped and followed by an oral vitamin K antagonist (VKA). Administration of heparins or fondaparinux should overlap during at least 5 days with that of VKA. The parenteral drug is stopped when the level of anticoagulation induced by the VKA has reached an international normalised ratio (INR) of 2.0 on two consecutive tests. VKA is continued for the remaining course of VTE treatment with ongoing INR monitoring of anticoagulant activity [36].

Single-drug approach with rivaroxaban or apixaban

Patients are initiated on rivaroxaban or apixaban as monotherapy without the need for ongoing monitoring. Both drugs are initiated at a high dose, which is reduced after the initial period of treatment. The recommended dose of rivaroxaban for the initial treatment of acute DVT or PE is 15 mg twice daily for the first three weeks followed by 20 mg once daily for the continued treatment and prevention of recurrent DVT and PE [37]. The recommended dose of apixaban for the treatment of acute DVT and treatment of PE is 10 mg taken orally twice daily for the first 7 days followed by 5 mg taken orally twice daily [38].

Sequential drug approach—heparin followed by dabigatran

The recommended daily dose of dabigatran is 300 mg taken as one 150 mg capsule twice daily following treatment with a parenteral anticoagulant for at least 5 days. The duration of therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding [39].

National Institute for Health and Care Excellence (NICE) recommendations

NICE recommends that therapeutic anticoagulation should be initiated immediately, preferably with a LMWH, fondaparinux, rivaroxaban, or UFH [36, 40, 41]. The recent approval of apixaban and dabigatran are not included in the NICE guideline. NICE guidelines make specific recommendations on the treatment of patients with severe renal impairment or established renal failure that include the use of UFH with dose adjustments based on the activated partial thromboplastin time and recommendations on how to use LMWH.

Thrombolysis

Thrombolysis—lysis of a thrombus by pharmacological stimulation of fibrinolysis—is conceptually attractive, with the goal of restoring patency in occluded veins, potentially reducing post-thrombotic syndrome (PTS).
 
The CaVent randomised trial compared catheter-directed thrombolysis with standard therapy for iliofemoral deep vein thrombosis (DVT) and found reductions in PTS at 2 years. Thrombolytic therapy increased vein patency at 6 months (66% vs 47%) and was associated with significantly less PTS at 24 months (41% vs 56%). Thrombolysis was associated with more bleeding, and there was no reduction in VTE recurrence or in mortality [42]. A follow up analysis performed after five years demonstrated that the patients who underwent thrombolysis had a persistent and increased clinical benefit, with PTS being present in 43% of the thrombolysis group and 71% of those undergoing standard therapy [55]. In contrast, the ATTRACT study, comparing pharmacomechanical thrombolysis in proximal DVT (femoral or above) showed no benefit of intervention over standard care (PTS present in 47% vs 48% at 2 years, respectively) [56]. The optimal endovascular thrombolytic approach needs further investigation.
 
NICE state that catheter-directed lysis may be useful if patients meet all of the following criteria: iliofemoral DVT, symptoms for fewer than 14 days, good functional status, life expectancy greater than 1 year, and low risk of bleeding [36].
 
There is good evidence describing the systemic administration of thrombolysis for submassive PE. Randomised trials have shown that systemic thrombolysis does not reduce mortality and is associated with a greater risk of bleeding than standard anticoagulation [34]. Thrombolysis is recommended only for patients with PE who experience haemodynamic compromise or deterioration while receiving standard anticoagulant therapy [36].

NICE recommendations [36] are:

For DVT

  • Consider catheter-directed thrombolytic therapy for patients with symptomatic iliofemoral DVT who have:
    • symptoms of fewer than 14 days' duration and
    • good functional status and
    • a life expectancy of 1 year or more and
    • a low risk of bleeding

For PE

  • Consider pharmacological systemic thrombolytic therapy for patients with PE and haemodynamic instability
  • Do not offer pharmacological systemic thrombolytic therapy to patients with PE and haemodynamic stability

Inpatient versus outpatient treatment of VTE

Traditionally, VTE treatment required hospitalisation for administration of heparin. With the advent of LMWH, outpatient management of DVT was shown to be possible, with evidence from a meta-analysis of six randomised trials comparing outpatient LMWH treatment with inpatient treatment demonstrating the acceptable safety and efficacy profile of this approach [43]. Management of DVT through outpatient services is now common in the UK. This treatment approach improves quality of life and reduces health care system costs. Patients with DVT are unlikely to be suitable for outpatient treatment if they have severe symptoms, renal impairment, poor social circumstances, or a high risk of bleeding [34].

For patients with PE, outpatient management is not as widely accepted, but is standard practice in some hospitals. Meta-analysis has shown that several prediction rules accurately select patients who are at low risk of death and therefore are potentially appropriate for outpatient PE management [44].