Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons

Abstract

Objective To analyse clinical outcomes with new oral anticoagulants for prophylaxis against venous thromboembolism after total hip or knee replacement.Design Systematic review, meta-analysis, and indirect treatment comparisons. Medline and CENTRAL (up to April 2011), clinical trials registers, conference proceedings, and websites of regulatory agencies. Data sourcesStudy selection Randomised controlled trials of rivaroxaban, dabigatran, or apixaban compared with enoxaparin for prophylaxis against venous thromboembolism after total hip or knee replacement. Two investigators independently extracted data. Relative risks of symptomatic venous thromboembolism, clinically relevant bleeding, deaths, and a net clinical endpoint (composite of symptomatic venous thromboembolism, major bleeding, and death) were estimated using a random effect meta-analysis. RevMan and ITC software were used for direct and indirect comparisons, respectively.Results 16 trials in 38 747 patients were included. Compared with enoxaparin, the risk of symptomatic venous thromboembolism was lower with rivaroxaban (relative risk 0.48, 95% confidence interval 0.31 to 0.75) and similar with dabigatran (0.71, 0.23 to 2.12) and apixaban (0.82, 0.41 to 1.64). Compared with enoxaparin, the relative risk of clinically relevant bleeding was higher with rivaroxaban (1.25, 1.05 to 1.49), similar with dabigatran (1.12, 0.94 to 1.35), and lower with apixaban (0.82, 0.69 to 0.98). The treatments did not differ on the net clinical endpoint in direct or indirect comparisons.Conclusions A higher efficacy of new anticoagulants was generally associated with a higher bleeding tendency. The new anticoagulants did not differ significantly for efficacy and safety.

Direct Oral Anticoagulants Vs. Enoxaparin for Prevention of Venous Thromboembolism Following Orthopedic Surgery: A Dose–Response Meta‐analysis

“…The availability of different regimens of comparators complicates an integrated assessment of the overall efficacy and safety of new agents relative to the current standard of care, as well as indirect comparisons among the new agents, but this factor has not always been considered in published meta‐analyses for single1, 2, 3, 4, 5, 6, 7 or multiple8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 agents. Dose regimen of the comparator has been acknowledged as a potential source of heterogeneity for a number of previous analyses 1, 2, 3, 5, 6, 10, 11, 12, 13, 14, 18.…”

The necessity of pharmacological prophylaxis against venous thromboembolism in major joint arthroplasty

“…A recent systematic review and meta-analysis concluded that the risk of symptomatic VTE was lower with rivaroxaban [relative risk (RR) 0.48; 95 % CI 0.31-0.75] and similar with dabigatran, when compared with enoxaparin. However, the RR of clinically relevant bleeding was higher with rivaroxaban (RR 1.25; 95 % CI 1.05-1.49) and similar with dabigatran (RR 1.12; 95 % CI 0.94-1.35) [9]. These figures suggest that chemical agents with a greater efficacy in VTE prophylaxis come at the cost of a higher risk of bleeding [9][10][11].…”

“…However, the RR of clinically relevant bleeding was higher with rivaroxaban (RR 1.25; 95 % CI 1.05-1.49) and similar with dabigatran (RR 1.12; 95 % CI 0.94-1.35) [9]. These figures suggest that chemical agents with a greater efficacy in VTE prophylaxis come at the cost of a higher risk of bleeding [9][10][11]. Rivaroxaban may also be more cost-effective than enoxaparin, with a 30-day course of 10 mg rivaroxaban costing £63.00, compared with £121.20 for a 30-day course of 40 mg enoxaparin [12].…”

Primary Joint Arthroplasty Surgery: Is the Risk of Major Bleeding Higher in Elderly Patients? A Retrospective Cohort Study

“…Even though elderly patients are considered at higher risk for bleeding and venous thromboembolism (5,7,10) most studies that assess safety and efficacy of VTE prophylaxis after major orthopedic surgery did not include an independent analysis or special considerations for this population (6,13,14,(22)(23)(24)(25)(26). Therefore, recommendations of dose adjustments are only based on the assumption of a physiological impairment of renal and hepatic function that occurs with age, but not on objective evidence of the increased risk of bleeding in this group of patients (15,(27)(28)(29).…”

“…Despite that numerous studies have assessed the efficacy and safety of different anticoagulant agents in general population (12)(13)(14), there is still a lack of evidence regarding its use in special populations such as elderly patients, considering that patients who are candidates to major orthopedic surgery are frequently older than 65 years (10,15,16).…”