Prophylaxis in MEDical Patients with ENOXaparin - MEDENOX

Description:

This randomized, double-blind, multicenter study compared two daily doses of subcutaneous enoxaparin with placebo for prevention of thromboembolism in patients hospitalized for acute medical illnesses.

Hypothesis:

Enoxaparin will reduce the risk of venous thromboembolism in hospitalized patients with acute medical illnesses.

Study Design

Study Design:

Patients Enrolled: 1,102
NYHA Class: 27% class III; 10% class IV
Mean Follow Up: 110 days
Mean Patient Age: mean age 73 ± 10 years
Female: 50

Patient Populations:

Medical patients >40 years of age with a projected hospital stay of at least six days, no prolonged immobilization, and one of the following illnesses: class III or IV heart failure, acute respiratory failure not requiring mechanical ventilation, acute infection without shock, acute rheumatic or musculoskeletal disorder, or inflammatory bowel disease. Patients with any but the first two diagnoses also had to have a clinical risk factor for thromboembolism, including age >75, cancer, previous venous thromboembolism, obesity, varicose veins, hormone therapy, or chronic heart or respiratory failure.

Exclusions:

Pregnancy, stroke or major surgery within three months, contrast allergy, renal failure, HIV infection, uncontrolled hypertension, active peptic ulcer disease, bacterial endocarditis, thrombocytopenia, hypersensitivity to heparin, known thrombotic diathesis, and requirement for anticoagulation therapy

Primary Endpoints:

Occurrence of venous thromboembolism (DVT, pulmonary embolism, or both) between study days 1 and 14. Venous thrombosis was assessed by venography whenever possible, or ultrasonography when venography was infeasible. Pulmonary embolism, when clinically suspected, was diagnosed by perfusion scanning, pulmonary angiography, or computed tomography.

Secondary Endpoints:

Venous thromboembolism between days 1 and 110, death and major and minor hemorrhage

Drug/Procedures Used:

Patients were randomized to subcutaneous enoxaparin 20 mg daily, 40 mg daily, or placebo, for the duration of hospitalization (6-14 days). Most patients were admitted for congestive heart failure, acute infectious process, or other acute respiratory illness.

Concomitant Medications:

Intramuscular injections and treatment with nephrotoxic agents (e.g., gentamicin) were not permitted. Enrolling centers were discouraged from using nonsteroidal anti-inflammatory agents. Support stockings and physical therapy were allowed according to usual clinical practices.

Principal Findings:

Of 1,102 enrolled patients, 866 (79%) completed assessment for deep-vein thrombosis (DVT) by venography or ultrasonography, and were included in the primary analysis. At day 14, venous thromboembolism was significantly less common in the enoxaparin 40 mg/day group compared with placebo (5.5% vs. 14.9%, p<0.001). Venous thromboembolism was equally likely in placebo or enoxaparin 20 mg/day patients (14.9% vs. 15.0%, p=NS).

Only four pulmonary emboli occurred—three in the placebo group and one in the low-dose enoxaparin group. The difference between 40 mg and placebo groups on the primary outcome was maintained to 110 days. There were no differences between study groups in death, hemorrhage, or other adverse events.

Interpretation:

Enoxaparin 40 mg qd, but not 20 mg qd, was associated with a significant reduction in venous thromboembolism—primarily asymptomatic DVT—compared with placebo when used in patients hospitalized with acute medical illnesses.

References:

Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 1999;341:793-800.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism, Acute Heart Failure, Angiography, Nuclear Imaging

Keywords: Neoplasms, Inflammatory Bowel Diseases, Pulmonary Embolism, Respiration, Artificial, Venous Thromboembolism, Risk Factors, Varicose Veins, Thromboembolism, Enoxaparin, Phlebography, Heart Failure, Obesity


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