Although the risk for venous thromboembolism (VTE) in hospitalized patients is often thought of as a complication of surgery, recent evidence suggests that hospitalizations for acute medical illnesses, including cardiac, respiratory, and infectious conditions, account for a similar proportion of VTE episodes. Interestingly enough, two thirds of fatal pulmonary embolism occur in medically ill patients.1
Pharmacologic thromboprophylaxis has been proven to reduce the incidence of venous thromboembolism in both surgical patients and acutely ill medical patients.2 In surgical patients, thromboprophylaxis has been shown to reduce the incidence of fatal pulmonary embolism and the rate of death from any cause.3 In medical patients, the Prophylaxis in Medical Patients with Enoxaparin (MEDENOX) study has confirmed that prophylaxis with low-molecular-weight heparins (LMWHs) can prevent VTE.4
In this recently published international, multicenter, randomized, double-blind, parallel-group study (LIFENOX), the authors included 193 sites in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia.5 The study randomized hospitalized, acutely ill medical patients (N=8323) to Graduated Elastic Stockings (GES) plus enoxaparin 40 mg subcutaneous once daily or to GES plus placebo for 10 ± 4 days. Eligible patients had to be ≥40 years of age and recruited within 48 hours of hospitalization for heart failure, active cancer, or severe systemic infection. The final intention-to-treat population included 8307 patients (all from outside United States and Europe). The study drug was discontinued in the event of creatinine clearance of <30 ml per minute, thrombocytopenia with a platelet count of <50,000 per cubic millimeter, definite venous thromboembolism requiring anticoagulant treatment, or proven heparin-induced thrombocytopenia.
The primary efficacy outcome was 30-day all-cause mortality and the primary safety outcome was the incidence of major bleeding up to 48 hours after receiving the last dose of study drug. The 30-day all-cause mortality was similar among both groups [4.9% of the GES plus enoxaparin group died within thirty days of randomization versus 4.8% of the GES plus placebo group; RR 1.0 (95% CI: 0.8-1.2)]. There was also no difference in the incidence of major bleeding between groups [0.4 GES plus enoxaparin vs. 0.3% GES plus placebo; RR 1.4 (95% CI: 0.7-3.1)].
Although this trial is considered a negative one, we should keep in mind that the study was conducted entirely at sites outside of the United States and Europe, with 74% of patients enrolled coming from India or China. Did genetic factors impact the results or are medical patients just inherently different than surgical patients?
1. Alikhan R, Peters F, Wilmott R, et al. Fatal pulmonary embolism in hospitalized patients: a necropsy review. J Clin Pathol 2004;57:1254-7.
2. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Guidelines (8th Edition). Chest 2008;133(6 Suppl):381S-453S.
3. Kakkar VV, Corrigan TP, Fossard DP, et al. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. Lancet
4. Samama MM, Cohen AT, Darmon JY, et al. A ...