New guidelines on the diagnosis and treatment of venous thromboembolism (VTE) were recently jointly issued by the American Academy of Family Physicians and the American College of Physicians. The guidelines are based on a systematic review of the evidence and are published, along with the systematic reviews, in the 2/2007 and 3/2007 issues of the Annals of Internal Medicine.
Part 2 Treatment
The treatment recommendations are summarized as follows:
Low-molecular-weight heparin (LMWH), as opposed to unfractionated heparin, should be used whenever possible for the initial inpatient treatment of DVT; either is an appropriate choice for initial inpatient treatment of PE. The authors note the importance of achieving therapeutic anticoagulation quickly in patients with VTE. In previous trials of unfractionated heparin, this was not accomplished and instead, many patients had both subtherapeutic and supratherapeutic levels. This is contrasted with LMWH with which it is possible to reliably achieve therapeutic anticoagulation quickly. The current evidence, based on systematic reviews, shows that LMWH is at least as effective as unfractionated heparin in the treatment of PE but further trials need to be completed to establish it as the preferred treatment. There is, however, consistent evidence demonstrating both mortality benefit and a lower risk of major bleeding in trials of LMWH as the initial therapy of DVT.
Outpatient treatment of DVT, and possibly PE, with LMWH is safe and cost-effective for carefully selected patients, and should be considered if the required support services are in place. The cited studies for this recommendation had strict inclusion and exclusion criteria; specifically, patients with previous VTEs, thrombophilic conditions or significant comorbid illnesses were excluded, as well as pregnant women and patients unlikely to adhere to outpatient therapy.
Compression stockings should be used routinely to prevent postthrombotic syndrome, beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis. In the trials examining the use of compression stockings, there was a greater than 50% relative risk reduction in the incidence of postthrombotic syndrome. No difference was noted between the use of over-the-counter stockings and custom-fit stockings.
There is insufficient evidence to make specific recommendations for the types of anticoagulation management of VTE in pregnant women. There is a fivefold increased risk of VTE during pregnancy but there is not adequate evidence to guide the treatment choice in this population. It is clear that Vitamin K antagonists should be avoided during pregnancy since these cross the placenta and are associated with embryopathy between 6 and 12 weeks gestation and fetal bleeding at time of delivery. LMWH and unfractionated heparin do not have these associations.
Anticoagulation should be maintained for 3 to 6 months for VTE secondary to transient factors, and for more than 12 months for recurrent VTE. While the appropriate duration of recurrent or idiopathic VTE is not definitively known, there is evidence of substantial benefit for extended-duration therapy. In a pooled analysis comparing lengths of anticoagulation there was a trend toward fewer recurrences with longer treatment but the confidence interval crossed 1. The evidence for extended-duration therapy only has follow-up to 4 years and the risk-benefit ratio of continuous, conventional anticoagulation may change with longer treatment. As always, the clinician must weigh the benefits, harms and patient preferences when making deciding on the length of anticoagulation.
LMWH is safe and efficacious for the long-term treatment of VTE in selected patients (and may be preferable for patients with cancer). LMWH may be useful in patients in whom the INR is difficult to control.
Finally, the study examined the modalities of vena cava filters and catheter-directed thrombolyis but did not make recommendations due to the insufficient evidence in these areas. There is a single randomized trial that addressed the incidence of VTE recurrence after vena cava filter placement. Patients were followed for 2 years and placed on anticoagulation. While there was a slight reduction in symptomatic PE when compared with anticoagulation alone, there was also a significant increase in recurrent DVT. With regards to catheter-directed thrombolysis, most of the studies are observational or case series; there is one small randomized trial comparing this therapy to conventional sequential anticoagulation and it suggests that, in well-chosen patients, this treatment may be efficacious.
Qaseem A et al. Current diagnosis of venous thromboembolism in primary care: A clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med 2007 Mar 20; 146:454-8.
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