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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Apixaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials

XM Li, SG Sun, and WD Zhang.

Review published: 2012.

CRD summary

The authors concluded that available evidence suggested that apixaban was more effective than recommended dose of enoxaparin and had a similar safety profile for thromboprophylaxis after hip and knee arthroplasty. The conclusions reflect the evidence presented and are reliable.

Authors' objectives

To compare the efficacy and safety of apixaban versus enoxaparin for prevention of venous thromboembolism after total hip or knee arthroplasty.

Searching

PubMed, The Cochrane Library, EMBASE, China Biological Medical Literature, Countries Journal full-text, VIP and Wanfang databases were searched from inception to March 2012. Search terms were reported. No language restrictions were applied. Reference lists of relevant articles and reviews were handsearched. Experts in the field were contacted.

Study selection

Randomised controlled trials (RCTs) that compared efficacy and safety of apixaban with enoxaparin for thromboprophylaxis in patients (of any age) who underwent total hip or knee arthroplasty were eligible for inclusion. Experimental trials and trials that focused on pharmacokinetic or pharmacodynamic variables were excluded. Primary outcome measures were efficacy (all venous thromboembolism and all-cause mortality) and safety (bleeding events, categorised as major, clinically relevant non-major or minor events). Secondary outcome measures were major venous thromboembolism, non-fatal pulmonary embolism and mortality.

Three studies included participants with total knee arthroplasty and one study included participants with total hip arthroplasty. Treatments were comparable across studies: apixaban (2.5mg, orally twice daily, started 12 to 24 hours after closure of the surgical wound, three studies; 2.5mg, 5mg or 10mg orally twice daily, started 12 to 24 hours after completion of the surgery, one study); enoxaparin (40mg, subcutaneous injections once daily with the first dose started 12 hours (within three hours) before surgery, two studies; 30mg, subcutaneous injections twice daily, started 12 to 24 hours after completion of the surgery, two studies).

Two reviewers independently assessed study eligibility for inclusion.

Assessment of study quality

Two reviewers independently assessed study quality using the Jadad scoring system for allocation concealment, randomisation, blinding, use of intention-to-treat analysis and withdrawals.

Data extraction

Two reviewers independently extracted data (using a predesigned form) on the proportion of patients with prespecified outcomes in order to calculate risk ratios (RR) with 95% confidence intervals (CI). Study authors were contacted for additional data where necessary. A third reviewer extracted data in case of disagreements; final agreement was achieved by consensus.

Methods of synthesis

Pooled risk ratios and 95% confidence intervals were calculated using random-effects (DerSimonian and Laird) meta-analysis. Heterogeneity was assessed using Χ² test and Ι² statistic. Publication bias was assessed using a funnel plot. Sensitivity analysis explored the influence of omitting studies one at a time.

Results of the review

Four randomised controlled trials (14,065 patients, range 1,471 to 5,765) were included: one phase II and three phase III studies. All the trials were of good quality (Jadad score 5).

Thromboprophylaxis with apixaban compared to enoxaparin was associated with significantly fewer venous thromboembolism and all-cause mortality (RR 0.63, 95% CI 0.42 to 0.95; 8,346 patients). There was evidence of high statistical heterogeneity (Ι²=84%).

There were no significant differences between thromboprophylaxis with apixaban and enoxaparin in safety outcomes for incidence of bleeding events: major bleeding (RR 0.76, 95% CI 0.43 to 1.33; 11,525 patients), clinically relevant non-major bleeding (RR 0.83, 95% CI 0.69 to 1.01; 11,525 patients) and minor bleeding (RR 0.93, 95% CI 0.79 to 1.09; 11,828 patients). There was evidence of statistical heterogeneity for major bleeding (Ι²=45%).

Apixaban was associated with significantly fewer total bleeding compared to enoxaparin (RR 0.88, 95% CI 0.79 to 0.99, Ι²=0%; 11,828 patients).

There were no significant differences between thromboprophylaxis with apixaban and enoxaparin in all secondary efficacy outcomes: major venous thromboembolism (Ι²=64%), non-fatal pulmonary embolism (Ι²=46%) and mortality (Ι²=0%). Sensitivity analyses did not alter overall treatment effects. The authors stated that there was no evidence of publication bias from the funnel plot (data not reported).

Authors' conclusions

Results suggested that apixaban was more effective than recommended dose of enoxaparin and had a similar safety profile for thromboprophylaxis after hip and knee arthroplasty.

CRD commentary

The review addressed a focused question; eligible study designs, patients, interventions and outcomes were prespecified. Several relevant databases were searched and efforts were made to identify unpublished studies. Review processes were conducted in duplicate which minimised risks of error and bias. Key study quality domains were assessed and studies reported to be of good quality. Heterogeneity was explored and study results combined using appropriate meta-analysis. Few studies were included but the overall sample size was adequate (14,065 patients). All of the included studies were funded by the branding pharmaceutical company of apixaban.

The authors’ conclusions reflect the evidence presented and are reliable.

Implications of the review for practice and research

Practice: The authors stated that available evidence suggested that apixaban (an effective direct factor Xa inhibitor given in a fixed, unmonitored oral dose) was an alternative to enoxaparin for preventing venous thromboembolism after hip and knee arthroplasty. They stated that apixaban should be contraindicated in patients susceptible to haemorrhage.

Research: The authors stated that additional head-to-head randomised controlled trials were needed to confirm the superior efficacy of apixaban over enoxaparin for prevention of venous thromboembolism after total hip or knee arthroplasty.

Funding

Not stated.

Bibliographic details

Li XM, Sun SG, Zhang WD. Apixaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials. Chinese Medical Journal 2012; 125(13): 2339-2345. [PubMed: 22882859]

Indexing Status

Subject indexing assigned by NLM

MeSH

Arthroplasty, Replacement, Hip /adverse effects /methods; Arthroplasty, Replacement, Knee /adverse effects /methods; Enoxaparin /therapeutic use; Humans; Pyrazoles /therapeutic use; Pyridones /therapeutic use; Randomized Controlled Trials as Topic; Venous Thromboembolism /etiology /prevention & control

AccessionNumber

12012037570

Database entry date

07/05/2013

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22882859

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