Venous thromboembolism: Highlights from recent studies

More than 600,000 cases of venous thromboembolism (VTE) occur annually in the United States.¹ Appropriate use of prophylaxis in patients with risk factors for VTE and prompt treatment of those with evidence of VTE are essential to reduce the substantial morbidity, mortality, and costs associated with this common and potentially life threatening disorder.^2,3

The complications of VTE include pulmonary embolism (PE) and chronic postthrombotic syndrome. PE is the third most common cardiovascular disease in the United States.⁴ It is associated with a high mortality rate, which in the presence of shock may be as high as 31% to 58%.^5,6 About 10% of hospital deaths are attributed to PE.^7,8 More than 90% of the patients who die of PE die within 2.5 hours of presentation.⁹ These statistics underscore the importance of VTE prophylaxis in at-risk patients, prompt recognition of clinical signs and symptoms of VTE, and appropriate treatment.

This Clinical Update presents highlights from recent studies on various aspects of VTE, such as the use of prophylaxis and predicting the outcome of acute PE.

DVT in patients with COPD

Shetty and associates¹⁰ analyzed data from a large US registry of patients with ultrasonography-confirmed deep venous thrombosis (DVT) and found that 12% of the patients had chronic obstructive pulmonary disease (COPD). Their study included 668 patients with COPD and 3907 patients without COPD.

Patients with COPD were older, more likely to be male, and more likely to be inpatients at the time of DVT diagnosis than were patients who did not have COPD. The patients with COPD were more likely to be admitted to the ICU, require mechanical ventilation, and receive inferior vena cava filters (Table). They also were more likely to have concomitant PE and congestive heart failure.

Guidelines for VTE prophylaxis

The American College of Chest Physicians (ACCP) has established guidelines for the prevention of VTE.^2,11 However, a recent study by Amin and associates¹² documented very low rates of adherence to VTE guidelines in acute-care hospitals in the United States. In fact, they found that about two thirds of atrisk medical patients are not receiving appropriate VTE prophylaxis at discharge.

Their study evaluated adherence to the 2000 ACCP guidelines¹¹ from 2002 to 2005. The analysis focused on at-risk medical patients and included data from 196,104 discharges from 227 hospitals. The patients were at least 40 years of age, were hospitalized for at least 6 days, and had no contraindications to anticoagulation. The overall rate of VTE prophylaxis was 61.8%; however, the rate of appropriate prophylaxis-that which is in accordance with the ACCP guidelines-was only 33.9%.

Of the discharged patients who did not receive appropriate prophylaxis, 38.4% received no prophylaxis at all, 4.7% received only mechanical prophylaxis, 6.3% received inappropriate doses, and 16.7% did not receive prophylaxis for the recommended duration.

The effectiveness of VTE interventions

Segal and associates¹³ reviewed 101 articles that reported the results of randomized controlled trials, systematic reviews of trials, and observational studies of the efficacy of various interventions in the treatment of DVT and PE. Highlights of their findings include:
• Low molecular weight heparin (LMWH) is at least as effective as unfractionated heparin in the treatment of PE and is modestly superior to unfractionated heparin in the initial treatment of DVT.
• Compared with unfractionated heparin, LMWH is cost-effective or cost-saving in the treatment of VTE.
• Early use of compression stockings reduces the risk of postthrombotic syndrome.
• The results of high-quality, randomized trials support the use of LMWH rather than oral anticoagulants, especially in patients with cancer.

Using fondaparinux and IPC to prevent VTE

Does combining pharmacological in patients undergoing abdominal surgery? Yes, according to Turpie and colleagues.¹⁴ They found that adding fondaparinux to the use of intermittent pneumatic compression (IPC) reduced the risk of VTE by nearly 70%.

Their study included 842 adults who underwent abdominal surgery. They were randomly assigned to receive subcutaneous fondaparinux (2.5 mg) or placebo, starting 6 to 8 hours after surgery, for 5 to 9 days. All patients received IPC. The follow-up period was 32 days.

The incidence of VTE was 1.7% in the fondaparinux group and 5.3% in the placebo group (risk reduction, 69.8%; P = .004). The incidence of proximal DVT also was significantly lower in the fondaparinux group (0.2% vs 1.7%; P = .037). Major bleeding events were more likely to occur with fondaparinux than with placebo (1.6% vs 0.2; P = .006). Such bleeding did not involve a critical organ and was not fatal.

The investigators concluded that the addition of fondaparinux to the use of IPC significantly reduces the risk of VTE in patients undergoing abdominal surgery.

Predicting outcome in acute PE

Jimenez and associates¹⁵ compared the ability of 2 prognostic models to predict short-term outcomes in 599 patients with acute PE. The PE Severity Index (PESI) was used to stratify patients into risk classes from 1 to 4, and the Geneva prediction rule was used to classify patients as low risk or high risk.

The 30-day mortality rate was significantly lower in patients classified as low risk than in those classified as high risk using either of the prediction models. This pattern was not observed for rates of nonfatal recurrent VTE or major bleeding. However, the PESI classified fewer patients as low risk than did the Geneva model. The area under the receiver operating characteristic curve was significantly higher for the PESI than for the Geneva score.

The investigators concluded that the PESI is better than the Geneva score at quantifying the prognosis of patients with PE. The PESI can identify those who are at very low risk for adverse events during the initial treatment of PE and, therefore, can be used to select patients for outpatient treatment.

Using D-dimer to predict PE mortality

Grau and associates¹⁶ studied 588 patients who had symptomatic PE. D-dimer levels were 500 to 2499 ng/mL in 47.8% of the patients, 2500 to 4999 ng/mL in 26%, and 5000 ng/mL or higher in 20.4%. At 3 months' follow-up, the mortality rate was 10.5%. PE was the cause of death in 18 patients (3%). The incidence of nonfatal VTE was 4.8%, and the incidence of nonfatal bleeding was 6%.

The relative risk of overall mortality was 1.91 in patients with the intermediate range of D-dimer levels and 2.94 in the highest D-dimer group, compared with patients with the lowest D-dimer levels. The risk of fatal PE was increased among those with the highest levels (odds ratio, 4.4); they also had an increased risk of death from other causes (odds ratio, 2.1). Higher Ddimer levels also were associated with more severe disease as assessed by clinical findings.

Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy, occurring in about 1% to 5% of patients.¹⁷ Complications include VTE, arterial thrombosis, skin necrosis, and limb gangrene.^18,19 Before the introduction of the direct thrombin inhibitors, the mortality rate associated with HIT was 20% to 25%.^20-22 Several recent studies have evaluated the efficacy of argatroban in the treatment of HIT in certain patient populations.

• Patients with CAD: Jang and colleagues²³ conducted a study of patients with HIT who had received heparin therapy for coronary artery disease (CAD). Argatroban was given to 121 patients; a control group consisted of 26 patients who did not receive any direct thrombin inhibitor.

They found that the use of argatrobanwas associated with a significantly lower incidence of new thrombosis (10% vs 30% in the control group). The composite end point of death, amputation, or new thrombosis was significantly reduced at 37 days. The incidence of bleeding was lower in the argatroban group. The authors concluded that argatroban is effective and safe in the management of HIT in patients with CAD.

• Acutely ill patients: Gray and associates²⁴ retrospectively studied 488 acutely ill patients with HIT, 390 of whom received argatroban. They found that argatroban reduced the risk of new thrombosis and thrombosis-related death. A benefit was also shown when the outcome measure was a composite end point of thrombosis-related death, amputation secondary to ischemic complications of HIT, or new thrombosis. Argatroban was not associated with a significant increase in the incidence of major bleeding. The investigators concluded that agratroban is safe and effective in managing HIT in acutely ill patients.

References:

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