There is currently limited information available
on the benefits and risks of extended thromboprophylaxis after hip fracture
surgery. SAVE-HIP3 was a randomised, double-blind study conducted
to evaluate the efficacy and safety of extended thromboprophylaxis
with the ultra-low molecular-weight heparin semuloparin compared
with placebo in patients undergoing hip fracture surgery. After
a seven- to ten-day open-label run-in phase with semuloparin (20
mg once daily subcutaneously, initiated post-operatively), patients
were randomised to once-daily semuloparin (20 mg subcutaneously)
or placebo for 19 to 23 additional days. The primary efficacy endpoint
was a composite of any venous thromboembolism (VTE; any deep-vein
thrombosis and non-fatal pulmonary embolism) or all-cause death until
day 24 of the double-blind period. Safety parameters included major
and clinically relevant non-major bleeding, laboratory data, and
treatment-emergent adverse events (TEAEs). Extended thromboprophylaxis
with semuloparin demonstrated a relative risk reduction of 79% in
the rate of any VTE or all-cause death compared with placebo (3.9% Cite this article:
Post-operative complications after total hip
or knee replacement can delay recovery, prolong hospitalisation, increase
rates of re-admission and, in the most severe cases, lead to long-term
disability or even death. In this analysis of pooled data from four
large, randomised, phase III clinical trials that compared the oral,
direct Factor Xa inhibitor rivaroxaban with subcutaneous enoxaparin
for the prevention of venous thromboembolism after total hip or
knee replacement (n = 12 729), the incidence of complications, including
bleeding and adverse events related to surgery (such as wound infection,
wound dehiscence and haemarthrosis) are reported. Interventions
and procedures relating to surgery are also compared between the
groups. Bleeding events, including excessive wound haematoma and
surgical-site bleeding, occurred at similar rates in the rivaroxaban
and enoxaparin groups. Over the total study duration, adverse surgical
events occurred at a similar rate in the rivaroxaban group compared
with the enoxaparin group after total knee replacement (2.26% This analysis shows that the incidence of adverse surgical events
with rivaroxaban was similar to enoxaparin.
In order to compare the effect of oral apixaban
(a factor Xa inhibitor) with subcutaneous enoxaparin on major venous
thromboembolism and major and non-major clinically relevant bleeding
after total knee and hip replacement, we conducted a pooled analysis
of two previously reported double-blind randomised studies involving 8464
patients. One group received apixaban 2.5 mg twice daily (plus placebo
injection) starting 12 to 24 hours after operation, and the other
received enoxaparin subcutaneously once daily (and placebo tablets)
starting 12 hours (± 3) pre-operatively. Each regimen was continued
for 12 days ( Apixaban 2.5 mg twice daily is more effective than enoxaparin
40 mg once daily without increased bleeding.
A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous thromboembolism in three studies of patients undergoing elective hip and knee replacement (RECORD programme). A pooled analysis of data from these studies (n = 9581) showed that rivaroxaban was more effective than enoxaparin in reducing the incidence of the composite of symptomatic venous thromboembolism and all-cause mortality at two weeks (0.4% vs 0.8%, respectively, odds ratio 0.44; 95% confidence interval 0.23 to 0.79; p = 0.005), and at the end of the planned medication period (0.5% vs 1.3%, respectively; odds ratio 0.38; 95% confidence interval 0.22 to 0.62; p <
0.001). The rate of major bleeding was similar at two weeks (0.2% for both) and at the end of the planned medication period (0.3% vs 0.2%). Rivaroxaban started six to eight hours after surgery was more effective than enoxaparin started the previous evening in preventing symptomatic venous thromboembolism and all-cause mortality, without increasing major bleeding.