Dabigatran etexilate (Pradaxa®) is an oral anticoagulant licensed in multiple countries, Europe and Canada, for the prevention of venous thromboembolic events (VTE) in patients undergoing total hip replacement surgery (THR) or total knee replacement surgery (TKR). The label recommendation for therapy initiation of dabigatran etexilate is a half dose given 1–4 hours after surgery. If this is not possible, then dabigatran etexilate should be started the day following surgery with the full dose. In the European pivotal Phase III clinical trials, this initial dosing was delayed until the day after surgery in 14% of the cases. This prompted a post hoc study to analyze if these patients received adequate thromboprophylaxis. Pooled efficacy data of major VTE events (composite of proximal DVT, symptomatic DVT, pulmonary embolism and VTE-related death) from the two European pivotal trials (RE-MODEL;
The oral direct thrombin inhibitor dabigatran etexilate (Pradaxa®) was recently approved in Europe for the prevention of venous thromboembolism (VTE) in patients undergoing elective total knee or total hip replacement surgery. In the Phase III RE-MODEL (
Dabigatran etexilate (Pradaxa®) is an oral direct thrombin inhibitor that was recently approved in Europe and Canada for the prevention of venous thromboembolism (VTE) in patients undergoing elective total knee replacement or total hip replacement surgery. Two pivotal clinical trials, RE-MODEL (
Dabigatran etexilate (Pradaxa®) is an oral direct thrombin inhibitor that was recently approved in Europe and Canada for the prevention of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) surgery. In the phase III studies, concomitant administration of selective nonsteroidal anti-inflammatory drugs (NSAIDs with t½≤12 hours) and acetylsalicylic acid (ASA; <
160 mg/day) was allowed during treatment with dabigatran etexilate or enoxaparin. Due to the potential additional anticoagulant activity of these concomitant therapies a separate post hoc analysis was conducted to investigate the bleeding risk in these patients. We analysed the pooled study population (8,135 patients) from the three phase III trials in THA and TKA surgery (RE-MOBILIZE, RE-MODEL and RE-NOVATE) for major bleeding events (MBE). All MBE, which included surgical site bleeds, were assessed by an independent, expert adjudication committee. We report the rates of MBE and odds ratios (with 95% confidence intervals [CI]) for comparison of the subgroup concomitantly treated with NSAID (or ASA) versus the subgroup of patients without concomitant antithrombotically active medication. The overall rate of MBE (with and without NSAIDs and ASA) was 1.4% [CI 1.0–1.9], 1.1% [0.7–1.5] and 1.4% [1.0–2.0] with dabigatran etexilate 220 mg, 150 mg, and enoxaparin, respectively. Of the total population, 57.4% of patients received concomitant antithrombotic treatment: 54.1% received NSAID and 4.7% received ASA. The MBE rate in patients receiving dabigatran etexilate or enoxaparin plus NSAIDs was similar to the rate in patients taking only dabigatran etexilate or enoxaparin; 1.5% vs. 1.4% [OR 1.05; 0.55–2.01] for dabigatran etexilate 220 mg, 1.1% vs. 1.0% [OR 1.19; 0.55–2.55] for dabigatran etexilate 150 mg, and 1.6% vs. 1.2% [OR 1.32; 0.67–2.57] for enoxaparin. A similar pattern was seen in patients concomitantly receiving ASA; in this small group only a few patients with MBE were observed: 2 (1.6%) in the dabigatran etexilate 220 mg group, 2 (1.6%) in the 150 mg group, and 4 (3.0%) in the enoxaparin group. No relevant differences in risk for MBE were detected between treatments by co-medication subgroup or within treatment groups when comparing patients receiving dabigatran etexilate or enoxaparin only versus those concomitantly receiving NSAIDs or ASA. In conclusion, patients concomitantly receiving dabigatran etexilate and NSAIDs (with t½ ≤12 hours) or ASA (<
160 mg/day) have a similar risk of MBE to patients taking only dabigatran etexilate. These data support the use of dabigatran etexilate for the prevention of VTE in patients after THA or TKA, when concomitant use of NSAIDs or ASA (<
160 mg/day) is required.