Reduction of venous thromboembolism following prolonged prophylaxis with the low molecular weight heparin Certoparin after endoprothetic joint replacement or osteosynthesis of the lower limb in elderly patients

Abstract

The peri- and postsurgical thromboembolic prophylaxis with low molecular weight heparins is a well established therapy regimen, but the optimum duration of prophylaxis after surgery still remains uncertain. A few studies have pointed to the fact that the thromboembolic risk of high-risk patients persists longer than the in-hospital period correlating with respective hypercoagulatory conditions. The aim of the present study was to test if a prolongation of thromboprophylaxis with the low molecular weight heparin Certoparin further reduces the rate of thromboembolism in high-risk patients after orthopedic surgery. The "Long-term Thromboprophylaxis"-Study was a multicenter, randomized, double-blind, placebo-controlled trial. 360 patients who underwent endoprothetic joint replacement or osteosynthesis of the lower limb were initially enrolled, all of them received prophylactically 3000 U anti-Xa of Certoparin once daily for 14 days followed by randomization to prolonged Certoparin application or to placebo up to day 42. Patients were screened for deep vein thrombosis by sonography every week. Coagulation markers (fibrin monomers and D-dimers) were determined during the course of the study. Venous thromboembolism during the prolongation period was observed in 18 patients receiving placebo versus 8 patients of the prolonged Certoparin group (12.1% versus 5.0%, intention-to-treat sample). The analysis revealed a statistically significant difference in favor of Certoparin (p=0.020), which was confirmed by per-protocol analysis (14.2% versus 5.5%, p=0.012). The differences remained significant, if analyses considered only clinically symptomatic thromboembolic events (p=0.040). Patients who developed a thrombosis showed a strong increase of coagulation markers as compared to patients without subsequent thrombosis. The respective differentiation started around 18 days before diagnosis of thrombosis. Only one minor bleeding complication was observed during prolonged Certoparin prophylaxis. The present study shows that patients after joint replacement or osteosynthesis of the lower extremities have a persisting risk to develop thromboembolic complications beyond the routine duration of thromboprophylaxis. Extended prophylaxis with Certoparin resulted in a significantly lower rate of thromboembolism and should be strongly recommended.

Incidence, risk profile and morphological pattern of venous thromboembolism after prostate cancer surgery

“…Beneficial effects of prolonged heparin prophylaxis have been described in other high-risk patient groups, such as those undergoing surgery for malignant disease other than prostate cancer or orthopaedic surgery [24][25][26], resulting in a significantly lower incidence of VTE. Our data suggest that the concept of prolonged heparin prophylaxis after RPE should be prospectively evaluated.…”

Prospective, Non-interventional Study on the Real-World Use of Certoparin in Daily Practice—The PROMEMBER Study

“…This is likely based on the physician's assessment as to the type of intervention/surgery and the assumed thromboembolic risk: patients receiving a reduced duration of prophylaxis might have undergone less severe interventions (such as arthroscopy) and one might question whether or not the particular patient should have received any prophylaxis. On the other hand, a prolonged prophylaxis (30%-39% of patients) has been, while not being covered by the labeling, documented to be effective in clinical studies 2 and recommended in current guidelines 1 because of the persistently elevated thromboembolic risk.…”

“…Within this context, there were a number of predefined objectives: (1) to determine the incidence of symptomatic thromboembolic events; (2) to determine the incidence of major bleeding complications; (3) to describe use of certoparin preparations, dosing, and duration of treatment in different indications and its comparison with SPC; and (4) to assess the timing of certoparin use before and after the surgical intervention.…”

Venous Thromboembolism in Orthopaedic Surgery

“…The ACCP guidelines recommend the optimal duration of VTE prophylaxis to be 28 to 35 days following THAs, and 10 to 14 days following TKAs (Kolb et al, 2003). Currently, the mean length of hospital stay is between 3 to 4 days, therefore full compliance with this recommendation is difficult for both the patient and the provider.…”