Dataset Information

Type of anaesthesia and the safety and efficacy of thromboprophylaxis with enoxaparin or dabigatran etexilate in major orthopaedic surgery: pooled analysis of three randomized controlled trials.

ABSTRACT:

Background

There has been a shift towards greater use of neuraxial over general anaesthesia for patients undergoing total hip or knee arthroplasty. Furthermore, suggestions that peripheral nerve block may reduce adverse effects have recently been put forward. Although older studies showed a reduction in venous thromboembolism (VTE) with neuraxial compared with general anaesthesia, this difference has not been confirmed in studies using effective current thromboprophylaxis. We used a large data set to investigate the pattern of anaesthesia usage, and whether anaesthesia type affects efficacy and bleeding outcomes of thromboprophylaxis overall, within each treatment group, or for the novel oral anticoagulant dabigatran etexilate versus enoxaparin.

Methods

Three previously reported trials compared 220 mg and 150 mg dabigatran etexilate once daily with enoxaparin after knee or hip arthroplasty. A pooled analysis was performed in patients receiving general or neuraxial anaesthesia, or the combination of either with peripheral nerve block (n = 8062). Outcome measures were major VTE plus VTE-related mortality, major bleeding and major plus clinically relevant bleeding events.

Results

General, neuraxial and combination anaesthesia were used in 29%, 52% and 19% of patients, respectively. Differences in efficacy and safety between anaesthesia subgroups were small and not significant, except for a slightly higher rate of major VTE and VTE-related mortality with general versus neuraxial anaesthesia (odds ratio: 1.40; 95% confidence interval: 1.03-1.90; p = 0.035) in the overall population. There were no significant effects of anaesthesia type on efficacy or safety of dabigatran etexilate versus enoxaparin.

Conclusions

Anaesthesia type did not greatly affect efficacy and safety outcomes in the pooled population of all three treatment groups. The efficacy and safety of dabigatran etexilate was comparable with enoxaparin, regardless of type of anaesthesia.

Trial registration

ClinicalTrials.gov identifiers: NCT00168805, NCT00168818, NCT00152971.

SUBMITTER: Rosencher N

PROVIDER: S-EPMC3444414 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

Type of anaesthesia and the safety and efficacy of thromboprophylaxis with enoxaparin or dabigatran etexilate in major orthopaedic surgery: pooled analysis of three randomized controlled trials.

Rosencher Nadia N Noack Herbert H Feuring Martin M Clemens Andreas A Friedman Richard J RJ Eriksson Bengt I BI

Thrombosis journal 20120618 1

<h4>Background</h4>There has been a shift towards greater use of neuraxial over general anaesthesia for patients undergoing total hip or knee arthroplasty. Furthermore, suggestions that peripheral nerve block may reduce adverse effects have recently been put forward. Although older studies showed a reduction in venous thromboembolism (VTE) with neuraxial compared with general anaesthesia, this difference has not been confirmed in studies using effective current thromboprophylaxis. We used a larg ...[more]

PMID: 22709460

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Project description:Dabigatran etexilate is an oral, reversible, direct thrombin inhibitor licensed for the prevention of venous thromboembolism and stroke prevention in patients with atrial fibrillation. The aim of this study was to investigate whether, and to what extent, a switch from enoxparin to dabigatran etexilate affects the pharmacokinetic (PK) and pharmacodynamic (PD) parameters and safety profile of dabigatran.Enoxaparin 40 mg was administered subcutaneously once daily for 3 days followed by a single dose of dabigatran etexilate 220 mg (test treatment) on day 4 in an open-label, two-way cross-over trial in healthy volunteers. Dabigatran plasma levels were measured using a validated high-performance liquid chromatography tandem mass spectrometry method. Anticoagulant activity was measured using a number of clotting tests, including prothrombinase-induced clotting time (PiCT), activated partial thromboplastin time (aPTT), ecarin clotting time (ECT), and diluted thrombin time (dTT).PK, PD, and safety data were available for 23 subjects for each treatment. The adjusted geometric mean test/reference ratio of area under the concentration-time curve for total dabigatran was 84% (90% confidence interval 67.2-105.0%) and 86% (67.0-110.0%) for maximum plasma concentration. The PiCT test/reference ratio, which represents the activity of enoxaparin and dabigatran, was elevated by approximately 15% for peak maximum effect ratio to baseline and total area under the effect curve (AUEC????) activity, suggesting that some anticoagulant activity of enoxaparin was still present. Enoxaparin pre-treatment increased the AUEC???? of activated partial thromboplastin time by approximately 14%. All other dabigatran-related PD markers were unaffected. Tolerability was good, with only mild and reversible adverse events during the treatment.Prior administration of enoxaparin did not meaningfully affect the PK or PD properties of dabigatran, and the switch from enoxaparin to dabigatran etexilate was well tolerated among the study subjects. These data support the safety of switching patients from enoxaparin to dabigatran etexilate.

Project description:AimThe aim of the present study was to analyse concomitant drug use and its association with outcome in patients (N = 17 701) receiving rivaroxaban or standard of care (SOC) for the prevention of venous thromboembolism after major orthopaedic surgery in the non-interventional, phase IV XAMOS (Xarelto® in the prophylaxis of post-surgical venous thromboembolism after elective major orthopaedic surgery of hip or knee) study.MethodsConcomitant drug use was at the discretion of the treating physician. Prespecified co-medications of interest were cytochrome P450 (CYP) 3A4/P-glycoprotein inhibitors/inducers, platelet aggregation inhibitors (PAIs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Crude event incidences were compared between rivaroxaban and SOC groups.ResultsCYP3A4/P-glycoprotein inhibitor/inducer use was infrequent, in contrast to PAI (~7%) and NSAID (~52%) use. Rivaroxaban was associated with a lower incidence of overall symptomatic thromboembolic events compared with SOC, regardless of co-medication use. In both treatment groups, PAI users, with higher age and prevalence of cardiovascular co-morbidities, had similar higher (>7-fold) incidences of symptomatic arterial but not venous thromboembolic events compared with non-users. NSAID use had no influence on thromboembolic events. However, odds ratios (ORs) for major bleeding events (European Medicines Agency definition) were higher in NSAID users compared with non-users in rivaroxaban [OR = 1.50; 95% confidence interval (CI) 1.06, 2.13] and SOC (OR = 1.70; CI 1.16, 2.49) groups. In PAI users, ORs for major bleeding events were no different from those of non-users in both the rivaroxaban (OR = 1.49; CI 0.84, 2.65) and SOC (OR = 1.46; CI 0.82, 2.62) groups.ConclusionsUse of NSAIDs in XAMOS was frequent and associated with a higher frequency of bleeding events in patients receiving rivaroxaban or SOC, although the benefit-risk profile of rivaroxaban compared with SOC was maintained.

Dataset Information

Type of anaesthesia and the safety and efficacy of thromboprophylaxis with enoxaparin or dabigatran etexilate in major orthopaedic surgery: pooled analysis of three randomized controlled trials.

Background

Methods

Results

Conclusions

Trial registration

Publications

Type of anaesthesia and the safety and efficacy of thromboprophylaxis with enoxaparin or dabigatran etexilate in major orthopaedic surgery: pooled analysis of three randomized controlled trials.

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