Peri and Post -Operative: Efficacy and Safety Profile

Efficacy and Safety Profile

Dahl OE et al. Thromb Haemost 1997;77:26–311.

Study Design:

Prospective, double-blind, randomised study to determine the benefits of prolonged thromboprophylaxis beyond hospital stay following hip replacement surgery. Patients undergoing hip arthroplasty (N=227) received initial prophylaxis with Fragmin, dextran and graded elastic stockings. On Day 7 patients received either s.c. Fragmin® (5,000 IU o.d.; n=117) or placebo (n=110) for 4 weeks.

Primary endpoints:

Prevalence of deep vein thrombosis  (DVT) and pulmonary embolism (PE) on Day 7, late prevalence of DVT and PE on Day 35 and incidence of DVT and PE from Day 7 to Day 35.

Safety endpoints:

Reoperation due to bleeding, wound haematoma, local haematomas at injection sites (>2 cm) and other bleedings were recorded.

Results:

The overall prevalence of DVT on Day 7 was 15.9%. By Day 35, the prevalence of DVT was higher in placebo-treated patients compared with Fragmin®-treated patients (31.7% vs. 19.3%, P=0.034). The incidence of DVT from Day 7 to Day 35 was also higher in placebo-treated patients compared with Fragmin®-treated patients (25.8% vs. 11.8%, P=0.017).

There were no patients with clinical symptoms of PE on Day 7. The incidence of symptomatic PE from Day 7 to Day 35 was 2.8% in the placebo-treated group compared with zero in the Fragmin®-treated group.

Conclusion:

Prolonged thromboprophylaxis with Fragmin® (5,000 IU o.d.) for 35 days significantly reduced the frequency of DVT after hip replacement surgery.

 

Kakkar W et al. Lancet 1993;341:259–2652.

Study Design:

Multicentre, randomised trial of patients undergoing major abdominal surgery, to compare the safety of two anticoagulants: Fragmin® (n=1,894) and standard heparin (SH; n=1,915). Each was given s.c. preoperatively and continued for a minimum of 5 postoperative days. Patients were followed up for at least 4 weeks.

Primary endpoints:

The frequency of major bleeding events and the efficacy of Fragmin® or SH in preventing postoperative venous thromboembolism (VTE).

Secondary endpoint:

Evidence of major bleeding postoperatively, wound haematomas, evacuation of haematomas, further surgery to control bleeding.

Results:

Major bleeding events occurred in 3.6% patients treated with Fragmin® and 4.8% patients treated with SH (P=0.10). There was a lower frequency of severe bleeding in the Fragmin® group than the SH group (1.0% vs. 1.9%, P=0.02) and wound haematoma (1.4% vs. 2.7%, P=0.007).

The requirement for further surgery following bleeding was reduced in the Fragmin® group, and incidence of injection site bruising was less frequent. The incidence of PE and DVT was the same for both Fragmin® and SH-treated patients, indicating that no significant differences were found in the efficacy of the two agents.

Conclusion:

The efficacy of Fragmin® and SH was similar in preventing postoperative VTE, however the incidence of bleeding events was lower with Fragmin®.

 

Hull et al. Arch Intern Med 2000;160:2208–22153.

Study Design:

A randomised, double-blind trial to determine the need for out-of-hospital thromboprophylaxis for patients who have hip arthroplasty. Of 569 patients, 199 were treated with preoperative Fragmin®, 190 were treated with postoperative Fragmin® and 180 received warfarin in hospital, followed by placebo out of hospital. Treatments were extended out of hospital for an interval of 35 days.

Primary endpoints:

DVT and proximal DVT, confirmed by venography.

Secondary endpoint:

Major, minor and trivial bleeding events, wound haematoma.

Results:

Of the patients receiving pre- and postoperative Fragmin®, the cumulative frequencies of proximal DVT were 3.1% (P=0.02) and 2.0% (P=0.007) compared to 9.2% of those receiving warfarin/placebo. The cumulative frequencies of all DVT events for pre- and postoperative Fragmin® groups were 17.2% (P<0.001) and 22.2% (P=0.003) compared to 36.7% who developed DVT in the warfarin/placebo group.

No major bleeding occurred during the extended prophylaxis interval, whilst rates of minor bleeding and wound haematoma were low and similar for all groups. Trivial bleeding was more frequent in the Fragmin® groups (17.6% preoperative, 20.0% postoperative) than the placebo group (8.9%), mostly due to bruising at the injection site.

Conclusion:

Fragmin® thromboprophylaxis for hip arthroplasty patients, administered for 35 days after hospitalisation, resulted in significantly lower frequencies of deep vein thrombosis compared with in-hospital warfarin therapy.

References

  1. Dahl et al. Thromb Haemost 1997;77:26–31.
  2. Kakkar V et al. Lancet 1993;341:259–265.
  3. Hull et al. Arch Intern Med 2000;160:2208–2215.

*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-0149.  June 2019