Subcutaneous Low-Molecular-Weight Heparin versus Standard Heparin and the Prevention of Thromboembolism in Medical Inpatients

Abstract

In a multicenter, double-blind clinical trial in 1,968 inpatients 1 daily subcutaneous administration of LMW heparin plus 2 placebo injections or 3 × 5,000 IU unfractionated (UF) heparin was given for 10 (8-11) days. The primary end point was the incidence of proximal deep-vein thrombosis or pulmonary embolism. Patients were assessed during the study period for development of proximal deep-vein thrombosis by compression sonography at days 1 and 10 and for pulmonary embolism by scintigraphy in symptomatic patients. Aim of the study was to demonstrate the equivalence of both treatment regimens. A total of 1,968 patients were randomized to receive UF or LMW heparin. Of these, 378 patients were excluded during the study period, so that 780 patients on UF and 810 on LMW heparin were included in the efficacy analysis. Four primary end points were observed with UF and 6 with LMW heparin, demonstrating the equivalence of treatments (p = 0.012). Additionally, pulmonary embolism was suspected as the cause of death in 6 patients who died during the study (3 per treatment group). A higher frequency of death (n = 32) was observed in the LMW-heparin group (p = 0.02) particularly documented in a part of the centers. Safety analysis showed a higher frequency of local pruritus, local erythema and subcutaneous hematoma, a higher increase in plasma levels of triglycerides, total cholesterol, alanine aminotransferase and aspartate aminotransferase, and a decrease of antithrombin III in patients receiving UF heparin. A decrease in platelet count (values ranging between 40,000 and 80,000/μl) was observed in 4 patients with UF and in none with LMW heparin. No severe thrombocytopenia was observed. Subcutaneous LMW heparin is as effective as UF heparin for prophylaxis of thromboembolism in bedridden, hospitalized medical patients.

Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis

“…Of these, 13 articles were excluded because of an inappropriate patient population (studies evaluating treatment of venous thromboembolism, n ϭ 8; acute coronary syndrome, n ϭ 4; hemodialysis, n ϭ 1); 11 articles were excluded because of the absence of comparison between UFH and LMWH; 32 articles were excluded because no quantitative results were reported on HIT or thrombocytopenia; 12 articles were excluded because of an undefined threshold for thrombocytopenia; 3 RCTs measuring thrombocytopenia were excluded because their definitions of thrombocytopenia were considered inadequate (platelet counts less than 70 ϫ 10 9 /L, less than 80 ϫ 10 9 /L, and less than 50 ϫ 10 9 /L, respectively). [6][7][8] One article 9 was excluded because of significant overlap of the reported patients between it and a previous study. One nonrandomized study comparing HIT incidence with LMWH and UFH was excluded because it had been published in abstract form only and appropriate data could not be extracted 10 ; 2 articles were meta-analyses; one article was a review.…”

Venous Thromboembolism in Hospitalized Patients With Heart Failure

“…A randomized, double-blind controlled trial in 442 hospitalized elderly patients bedridden for acute illness demonstrated similar efficacy of enoxaparin 20 mg once daily compared with LDUH 5000 U twice daily. 64 66 Although the results including all patients demonstrated equivalence between the 2 therapies in incidence of venographically detected VTE, in the subset of 206 patients with HF, enoxaparin was associated with a numerically lower incidence of VTE (9.7% versus 16.1%, Pϭ0.0139 for equivalence). No patients with HF developed PE during enoxaparin therapy, whereas 1 patient in the LDUH group was found to have PE on autopsy.…”

“…58,[61][62][63][64][65][66][67][68] A randomized, double-blind controlled trial in a high-risk group of 959 hospitalized medical patients compared enoxaparin 40 mg once daily with LDUH 5000 U three times daily. Enoxaparin was found to be at least as efficacious as LDUH with fewer adverse events.…”

Individual patient data meta‐analysis of enoxaparin vs. unfractionated heparin for venous thromboembolism prevention in medical patients

“…However, generalizing our results to include other LMWHs is difficult given the limited data available regarding comparative efficacies (most studies compare LMWHs with placebo or UFH) and the different regimens used. These results may not transfer directly to cases where other LMWHs did not show superiority compared with UFH for VTE prophylaxis in medical patients [25,26].…”