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Studies show promising results for oral VTE prophylaxes after joint arthroplasty
One drug study finds relationship between age and risk of VTE and bleeding was not a factor.
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Early research on oral prophylaxes indicate they are safe and effective in preventing venous thromboembolism following joint arthroplasty, and the dosage for one treatment may work regardless of patients’ age, gender or weight.
In a phase III, multicenter trial, Andreas A. Kurth, MD, and colleagues studied 2,076 total knee arthroplasty patients who received 40 mg of subcutaneous enoxaparin (Sanofi-Aventis), 150 mg of the oral anticoagulant dabigatran etexilate (Rendix, Boehringer-Ingelheim) or 220 mg of dabigatran etexilate daily. An evaluation of 75% of the patients revealed that both doses of the oral prophylaxis were as effective in preventing venous thromboembolism (VTE) and death as enoxaparin. They also reported total VTE and mortality rates of 37.7% for enoxaparin-treated patients and rates of 36.4% and 40.5% for the 220-mg and 150-mg doses of dabigatran etexilate, respectively.
A review of all of the patients also showed similar major bleeding rates (between 1.3% and 1.5%) for the three study groups.
“Oral administration of dabigatran etexilate once daily, given early in the postoperative period, was effective and safe for the prevention of total VTE in patients undergoing total knee replacement surgery,” they reported in their abstract.
Double-blind study
The double-blind study included patients with a mean age of 67 years and a mean weight of about 80 kg. Most of the patients were women, Kurth said during his presentation at the 8th European Federation of National Associations of Orthopaedics and Traumatology Congress.
Patients in the enoxaparin group received 40 mg a day beginning 12 hours before surgery. The dabigatran etexilate-treated patients took a half dose 1 to 4 hours after surgery and then began their respective full dosage on the following day.
“The primary endpoint was the composite of VTE and all causes of mortality during treatment,” Kurth said.
The investigators also determined the rate of proximal deep vein thrombosis (DVT) and/or pulmonary emboli (PE) and major blood loss. They found proximal DVT and/or PE rates of 2.6% for the 220 mg dabigatran etexilate group and 3.8% for the 150 mg group, while the enoxaparin group demonstrated a 3.5% rate.
The research also revealed one death in each study group, according to the abstract.
Investigators are also finding promising results with the oral Factor Xa inhibitor, rivaroxaban (Bayer Healthcare and Ortho-McNeil Pharmaceuticals Inc., a subsidiary of Johnson and Johnson). In three phase II trials, Ola E. Dahl, MD, PhD, and colleagues studied more than 1,000 patients who received either oral rivaroxaban (2.5 mg to 30 mg) or enoxaparin for 5 to 9 days following total hip or total knee arthroplasty.
The investigators found comparable safety and efficacy between enoxaparin and 5-mg to 20-mg daily doses of rivaroxaban. Moreover, they discovered no link between patients’ weight, gender or age and the dose/response between the treatment and clinically relevant bleeding or DVT, PE or death, according to their abstract.
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“Dose adjustment for age, gender and body weight will not be necessary with rivaroxaban, excluding the extremes (eg, mega-fat and very thin),” Dahl told Orthopaedics Today International.
To determine the efficacy of rivaroxaban, the investigators studied the rates of DVT, PE or death in 1,380 patients. To assess for safety, they noted any cases of clinically relevant bleeding in 1,854 patients who took the medication.
“Overall, logistic regression showed a positive dose/response relationship with rivaroxaban for clinically relevant bleeding (P<.001), and a flat relationship for the primary efficacy endpoint (P=.115),” the investigators wrote.
Age may impact VTE risk
They also found that age increased the risk of VTE. While DVT, PE or all-cause mortality occurred in 20.2% to 26.6% of patients older than 70 years, it was only noted in 9.4% to 17.3% of patients younger than 60 years. Similarly, 5.7% to 15.4% of patients over 70 had clinically relevant bleeding compared to 1.4% to 12% of those younger than 60 years.
After adjusting for age, the investigators found higher rates of DVT, PE and mortality in women, but found less frequent rates of clinical bleeding.
They also discovered no significant correlation between weight and safety and efficacy after adjusting for gender, age and study, and reported that weight did not impact the dose/response relationships.
While Dahl said that he did not know why weight did not change the dose/response relationship, he and his colleagues saw similar findings with other modern anticoagulants. “I have a simple speculation that blood volume in adult humans is roughly independent of weight,” he said.
For more information:References:
- Ola E. Dahl, MD, can be reached at the Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, London, SW3 6LR, England; +44-20-7351-8346; e-mail: oladahl@start.no. He is on a scientific steering committee linked to rivaroxaban and dabigatran development programs in major joint arthroplasty patients.
- Andreas A. Kurth, MD, can be reached at University Hospital Frankfurt/Main, Marienburgst. 2, 60528 Frankfurt/Main, Germany; +49-69-67050; e-mail: A.Kurth@em.uni-frankfurt.de.Orthopaedics Today International was unable to determine whether or not Kurth has any financial disclosures to report.
- Kurth AA, Dahl OE, Van Dijk, et al. A new oral anticoagulant, Dabigatran Etexilate, is effective and safe for the prevention of venous thromboembolism after total knee replacement. #F376.
- Dahl OE, Eriksson BI, Homering M, et al. The effect of patient age, gender and weight on the efficacy and safety of Rivaroxaban (BAY 59-7939) for the prevention of venous thromboembolism after major orthopaedic surgery. #F385. Both presented at the 8th European Federation of National Associations of Orthopaedics and Traumatology Congress. May 11-15, 2007. Florence.