What is the best choice for prophylaxis against VTE in medical inpatients?

Case

A 76-year-old gentleman is admitted for progressively worsening dyspnea, cough, and bilateral leg edema. Upon admission, his blood pressure is 150/90 mm/Hg, pulse 90 beats per minute, and respiration is 24 per minute.

Pertinent physical findings include jugular venous distension, bilateral crackles, S3 gallop, and 2+ bilateral lower extremity edema. The chest radiograph shows cardiomegaly and pulmonary edema. He is admitted to the hospital with a diagnosis of acute decompensated heart failure and starts aggressive medical therapy.

Overview

Approximately 2 million cases of deep-vein thrombosis (DVT) occur annually in the United States. Based on studies utilizing ventilation-perfusion scanning, half these patients likely have a silent pulmonary embolism (PE); of these, approximately 250,000 die.

The spectrum of venous thromboembolism (VTE), which includes DVT and PE, can vary from being asymptomatic to sudden death. Autopsy studies suggest a leading cause of sudden death in hospitalized medical patients is often a PE. There also are sequelae, such as chronic pulmonary hypertension, occurring in approximately 5% of PE cases, and post-thrombotic syndrome, occurring in approximately 40% of patients with DVT at two years.1

A recent study suggests DVT occurs three times more commonly in the outpatient setting. However, more than half of these patients were hospitalized in the three months prior.2 This is likely due to inadequate in-hospital prevention because of absence of prophylaxis, use of an unsuitable modality, insufficient dose of the drug, or ineffective duration of therapy. Inadequate and omitted VTE prophylaxis for medical patients was clearly demonstrated in the DVT Free Registry. This registry was created by 183 U.S. hospitals and included 5,451 patients, inpatients, and outpatients with ultrasound-confirmed DVT.

The number of medical inpatients who received prophylaxis in the 30 days prior to diagnosis was 28%—lower than the 48% of surgical patients.3 In a recent international registry, IMPROVE, only approximately 50% of hospitalized patients received prophylaxis.4

Virchow’s triad describes three underlying etiologic factors for thrombosis: stasis of blood flow, endothelial injury, and hypercoagulability. Established VTE risk factors reflect these underlying pathophysiologic processes. Important risk factors for VTE include increasing age, prolonged immobility, malignancy, major surgery, multiple trauma, prior VTE, and chronic heart failure.5

However, the magnitude of risk conferred by these and other risk factors varies (see Table 1, p. 35). It is not known how these factors interact to determine a patient’s individual VTE risk, but there is evidence it increases in proportion to the number of predisposing factors present.

In a recent systematic review of nine studies, including approximately 20,000 patients, prophylaxis reduced the rate of symptomatic VTE in at-risk hospitalized medical patients without increasing major bleeding.6