Bedridden Thromboprophylaxis: Efficacy and Safety Profile

Efficacy and Safety Profile

Leizorovicz A et al. Circulation 2004;110:874–8791.

Study Design:

An international, multicentre, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of Fragmin® for the prevention of venous thromboembolism (VTE) in acutely ill medical patients (N=3,706). Patients were assigned to receive either s.c. Fragmin® (5,000 IU o.d.; n=1,518) or placebo (n=1,473) for 14 days and were followed up for 90 days.

Primary endpoint:

Incidence of VTE by Day 21.

Secondary endpoints:

Mortality by Days 14, 21 and 90; symptomatic deep vein thrombosis (DVT) or asymptomatic DVT at Day 21; major and minor bleeding; drug-related allergic reactions; thrombocytopenia by Day 21; symptomatic VTE at Day 90.

Results:

Patients treated with Fragmin® had a lower incidence of VTE at Day 21 compared with patients treated with placebo (2.77% vs. 4.96%, P=0.0015). This observed benefit was maintained at 90 days. The incidence of proximal DVT by Day 21 was lower among patients receiving Fragmin® than those receiving placebo (symptomatic: 0.11% vs 0.40%; asymptomatic: 1.79% vs. 3.65%). 2 placebo and no Fragmin® patients had fatal pulmonary embolism ( PE) by Day 21. There was no significant difference in mortality between both groups at 14, 21 or 90 days. Patients treated with Fragmin® had a higher incidence of major bleeding than patients treated with placebo (0.49% vs. 0.16%, P=0.15).

Conclusion:

Fragmin® reduced clinically important VTE with a low risk of bleeding in acutely ill medical patients.

 

Kucher et al. Arch Intern Med 2005;165:341–3452.

Study Design:

Retrospective analysis of the PREVENT trial to determine if fixed rather than weight-based dosages of Fragmin® are as effective and safe for the prevention of VTE in obese and elderly medical patients. Obese patients (n=1,118) and elderly patients (n=1,226) received either Fragmin® (5,000 IU, o.d.) or placebo.

Primary endpoint:

Symptomatic VTE, fatal PE, sudden death or asymptomatic proximal DVT by Day 21.

Results:

In obese patients, primary end point incidence was higher in those treated with placebo rather than Fragmin® (4.3% vs. 2.8%), however, no difference was observed between obese and non-obese patients who reached the primary endpoint receiving either treatment. In elderly patients (≥ 75 years old), primary end point incidence was higher in those treated with placebo rather than Fragmin® (8.0% vs. 4.2%). The incidence of PE and DVT was higher in elderly patients compared to younger patients; this was the case in both the Fragmin® and placebo groups.

Fragmin® did not increase incidence of major bleeding events by Day 21 in obese (0% vs. 0.7% placebo; P=0.99) and in elderly (1.1% vs. 0.7% placebo; P=0.12) patients.

Conclusion:

A fixed dose of Fragmin® (5,000 IU, o.d.) was as effective in VTE prevention at Day 21 in obese vs. non-obese and in elderly vs. younger hospitalised patients. With respect to safety, no significant differences in mortality or major bleeding were observed between Fragmin® and placebo treated patients, in both the obese and elderly subgroups.

References

  1. Leizorovicz et al. Circulation 2004;110:874–879.
  2. Kucher et al. Arch Intern Med 2005;165:341–345.

*Including, but not limited to: congestive cardiac failure (NYHA class III or IV), acute respiratory failure or acute infection, who also have a predisposing risk factor for VTE such as age over 75 years, obesity, cancer or previous history of VTE.~
†In patients with chronic renal insufficiency or acute renal failure.

PP-FRA-GBR-0153.  June 2019