In the absence of prophylaxis and using different radiological screening tests, DVT rates have been reported in a significant percentage of medical patients.[14
] Using autopsy studies, 2.5% of 200 medically ill patients followed up prospectively with no prophylaxis, were observed to have fatal PE.[17
] Comparing unfractionated heparin (UFH) with placebo in medically ill patients, the rate of radiologically detected DVT was reduced significantly without bleeding complications.[15
LMWH was also compared with placebo in medically ill patients; in a randomized double-blind trial, Dahan and colleagues[14
] used enoxaparin once daily or placebo in 275 medical patients over the age of 60 years. The incidence of radiologically proven DVT was reduced from 9% in the placebo group to 3% in the group of patients receiving enoxaparin (P
= 0.03). Except for injection site hematoma that was more frequent in the LMWH group, there was no difference in major bleeding in the two groups.
The MEDENOX trial[16
] (prophylaxis in MEDical patients with ENOXaparin) was a randomized, double-blind, placebo-controlled study designed to study the value of LMWH at a two-dose level, in reducing the incidence of VTE in medical patients. Patients were older than 40 years with expected hospital stay of at least 6 days and had been recently immobilized for 3 days or less. Patients were admitted with acute heart failure, New York Heart Association (NYHA) class III or IV, or acute respiratory failure (but not requiring immediate ventilatory support). Other patients included in this study had one of the following three medical conditions: acute infectious disease without septic shock, acute rheumatic disorder or an active episode of inflammatory bowel disease and at least one predefined VTE risk factor (age > 75 years, cancer, previous history of VTE, obesity, varicose veins, hormone replacement therapy and chronic heart or respiratory failure). A total of 1102 patients were enrolled, evaluable patients (n
= 866) were divided into three treatment groups: placebo, enoxaparin at a dosage of 20 mg and 40 mg, all given once daily subcutaneously. The incidence of radiologically proven VTE was reduced from 14.9% in the placebo group to 5.5% in the group that received enoxaparin at 40 mg (P
< 0.001), a risk reduction of 63%. However, there was no significant difference in the incidence of VTE between the group that received low dose enoxaparin (20 mg) and the placebo group. Additionally, there was no significant difference in major bleeding among the three groups.
In another study, Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients Trial (PREVENT), Leizorovicz and colleagues[19
] randomized 3706 medical patients to receive either 5000 IU of dalteparin once daily or placebo for 14 days. The patients underwent a bilateral compression ultrasound on day 21 to search for asymptomatic proximal thrombi. The incidence of VTE was reduced from 4.96% in the placebo group to 2.77% in the dalteparin group, an absolute risk reduction of 2.19% or a relative risk reduction of 45% (relative risk: 0.55; 95% CI: 0.38–0.80; P
= 0.0015). The observed benefit was maintained at 90 days. The overall incidence of major bleeding was low but higher in the dalteparin group (nine patients; 0.49%) compared with the placebo group (three patients; 0.16%).
A meta-analysis of seven randomized trials comparing prophylactic UFH or LMWH versus placebo in medically ill patients, excluding acute myocardial infarction or ischemic stroke, was performed.[20
] The primary end points were DVT detected at the end of the treatment period and clinical PE; other end points include death and major bleeding. More than 15,000 patients were included. A significant decrease in DVT and clinical PE was observed with heparins as compared to control (risk reductions: 56 and 58% respectively, P
< 0.001 in both cases), without a significant difference in the incidence of major bleedings or deaths. Above discussed studies indicate that VTE prophylaxis with UF or LMWH is safe and effective in high-risk medical patients.