Guidelines Focus on VTE Diagnosis and Treatment

By Diana Mahoney 

New venous thromboembolism guidelines aimed at primary care physicians emphasize the need for swift diagnosis and initial treatment with low-molecular-weight heparin over the unfractionated formulation. The guidelines are intended to help patients in their initial "front-line" treatment.

Compared with unfractionated heparin, low-molecular-weight heparin (LMWH) is associated with a reduced risk of major bleeding and mortality in the treatment of deep venous thrombosis (DVT), and as such "should be used whenever possible for the initial inpatient treatment" of these patients, according to the guidelines, which were issued jointly by the American Academy of Family Physicians and the American College of Physicians (Ann. Intern. Med. 2007;146:204-10).

Venous thromboembolism (VTE) presents a primary care challenge. Risk factors for the condition, such as recent hospitalization, surgery, trauma, and immobilization, are well known, but early diagnosis--which is critical to a successful outcome--is difficult because thromboembolic events are often "clinically silent," according to Dr. B. Gail Macik, of the division of hematology and oncology at the University of Virginia, Charlottesville.

While recent advances in diagnosis and prophylactic treatment are poised to have a significant impact on reducing VTE-associated mortality, they can only do so if they are well disseminated through the primary care ranks, which, historically, they have not been, said Dr. Macik, who was not involved in writing the new guidelines.

In fact, most management guidelines to date have been geared toward patients with difficult or complicated disease in specific health care settings, such as intensive care units, Dr. Macik noted. In contrast, the new guidelines offer "clinically relevant screening and treatment recommendations specifically for primary care physicians who are the most likely to have front line contact with [undiagnosed] VTE," she said. "As with most guidelines, these leave wiggle room for individual application, but the concise review and recommendation for care is very welcome."

The management recommendations are based on the findings of a comprehensive systematic literature review published in 2003 and updated by Dr. Jodi B. Segal and colleagues at the Johns Hopkins University Evidence-based Practice Center, Baltimore (Ann. Intern. Med. 2007; 146:211-22).

Key topics addressed by the recommendations for management include:

1. Home-based treatment. Patients who have adequate support at home can receive LMWH treatment on an outpatient basis. Data on the risks among inpatients versus outpatients demonstrate only slight differences in the rates of recurrent VTE, major bleeding, and death. However, most studies relevant to this question "excluded patients with previous VTE, thrombophilic conditions, or significant comorbidity, pregnant patients and patients unlikely to adhere to outpatient therapy," the authors wrote. Also, several of the studies allowed for brief inpatient admissions for stabilization prior to randomization to outpatient treatment.
2. Compression stockings. On the basis of evidence demonstrating a marked reduction in the incidence of postthrombotic syndrome among patients with DVT who wear compression stockings, the guidelines recommend the routine use of either over-the-counter or custom-fit stockings beginning 1 month after diagnosis of proximal DVT, and continuing for a minimum of 1 year. Of three randomized controlled trials that studied the use of compression stockings, the two that enrolled patients within 1 month of developing proximal DVT showed a significant reduction in postthrombotic syndrome, while no such benefit was seen in the one trial that enrolled patients 1 year after the DVT event, the authors reported, noting that "most diagnoses of post-thrombotic syndrome occurred early, within the first two years after DVT."
3. Pregnancy. Anticoagulation management during pregnancy is particularly important, as the risk of VTE in women during pregnancy is five times greater than the risk in nonpregnant women, the authors stated. However, the available data are insufficient to recommend specific therapies in pregnant women. The guideline does recommend avoiding vitamin K antagonists because they can cross the placenta and have been associated with fetal bleeding as well as embryopathy between 6-12 weeks' gestation. "Neither LMWH nor unfractionated heparin crosses the placenta, and neither is associated with embryopathy or fetal bleeding," the authors wrote.
4. Secondary and idiopathic VTE. For VTE secondary to transient risk factors, such as surgery, trauma, or immobilization, the available evidence indicates that patients may be well served with 3-6 months of oral anticoagulation therapy.
   
   With respect to idiopathic VTE, the available data suggest that extended duration anticoagulation therapy is associated with a reduced relative risk of recurrence, although the optimal duration is not known as the length of therapy in the trials varied substantially and the results reflect follow-up only to 4 years. Consequently, the guideline advises continuing anticoagulant therapy for more than 12 months for recurrent VTE but that providers should "weigh the benefits, harms, and patient preferences in deciding on the duration of anticoagulation."
5. Long-term treatment. When long-term treatment with LMWH is compared with vitamin K antagonists, the former is "safe and efficacious for the long-term treatment of VTE in selected patients, and may be preferable for patients with cancer," as studies have linked LMWH to a survival advantage in this population. Specifically, the data suggest that "LMWH may be a useful treatment for patients in whom INR [international normalized ratio] control is difficult."
6. Pulmonary embolism. Regarding pulmonary embolism treatment, "LMWH is at least as effective as unfractionated heparin," according to a review of the available evidence, thus either drug is appropriate for initial treatment, said Dr. Vincenza Snow, director of clinical programs and quality of care for the ACP. The authors did note, however, that additional trials are needed to more rigorously examine the efficacy of LMWH for pulmonary embolism.