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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].

Is recurrent venous thromboembolism after therapy reduced by low-molecular-weight heparin compared with oral anticoagulants?

G Ferretti, E Bria, D Giannarelli, P Carlini, A Felici, M Mandala, P Papaldo, A Fabi, M Ciccarese, F Cuppone, FL Cecere, C Nuzzo, E Terzoli, and F Cognetti.

Review published: 2006.

CRD summary

This review, which evaluated incidence of recurrent venous thromboembolism (VTE) events after treatment with low molecular weight heparin compared with oral anticoagulant therapy, found no significant difference in VTE events after cessation of therapy. The authors' conclusions may be slightly strong when

considering the possibility of bias in this review.

Authors' objectives

To evaluate whether the incidence of recurrent venous thromboembolism (VTE) events after therapy differs if the patient was treated with low molecular weight heparin (LMWH) compared with oral anticoagulant therapy (OAT).

Searching

MEDLINE (1966 onwards), the Cochrane Controlled Trials Register, the American Society of Haematology abstract database and the American Society of Clinical Oncology abstract database were

searched; the search terms were reported. Non-English language studies were excluded.

Study selection

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for the review.

Specific interventions included in the review

Interventions eligible for inclusion were those in which the patients were randomly allocated to long-term treatment with LMWH or OAT. The OATs evaluated were warfarin and acenocoumarol, and the INR ranges studied were 2.0 to 3.0 (10 studies) and 2.0 to 3.5 (1 study). The LMWHs investigated were enoxaparin, dalteparin, nadroparin, tinzaparin and bemiparin, and the doses given were 3,500 to 5,000 IU every day (qd), 85 to 175 IU/kg qd, 1,025 IU/10 kg twice daily, and 1 to 1.5 mg/kg qd. The treatment

periods lasted from 3 to 6 weeks and follow-up ranged from 3 to 9 weeks.

Participants included in the review

Studies of patients with objectively diagnosed symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) or both were eligible for inclusion. The proportion of patients with cancer in individual studies varied from 3.8 to 100%.

Outcomes assessed in the review

The primary outcome was the incidence of recurrent symptomatic VTE during treatment and follow-up.

How were decisions on the relevance of primary studies made?

It appears that two reviewers independently assessed the primary studies.

Assessment of study quality

Studies were assessed for adequacy of allocation concealment, double-blinding, blinding of the outcome assessors and use of intention-to-treat (ITT) analysis. The authors did not state how many reviewers performed the validity assessment.

Data extraction

Two reviewers independently extracted the data. The incidence of recurrent symptomatic VTE in each treatment arm was used to calculate the relative risk (RR) and its associated 95% confidence interval (CI) for each study.

Methods of synthesis

How were the studies combined?

The RRs for each study were pooled in a meta-analysis using fixed-effect and random-effect models. The analysis was weighted by the number of events in each treatment group in each study using the inverse variance and Mantel-Haenszel methods. All analyses used ITT data. If ITT data were not available, the

analysis was based on information provided by the individual study.

How were differences between studies investigated?

A chi-squared test was used to assess statistical heterogeneity between the studies. A subgroup analysis investigated effects in patients with cancer.

Results of the review

Eleven RCTs (n=2,907) were included in this review.

During active treatment, LMWH was associated with a statistically significant reduction in the risk of recurrent VTE compared with OAT (RR 0.63, 95% CI: 0.47, 0.83, p=0.001).

In a subgroup analysis of cancer patients alone (4 studies), during active treatment LMWH was also associated with a statistically significant reduction in the risk of recurrent VTE compared with OAT (RR 0.52, 95% CI: 0.35, 0.76, p=0.001).

Tests for heterogeneity showed that there was no evidence of statistically significant differences between the studies combined in each analysis.

No significant difference was found in the RR of recurrent symptomatic VTE after cessation of active treatment during the follow-up period for patients treated with OAT compared with LMWH.

Funnel plot analyses did not reveal any evidence of publication bias.

Authors' conclusions

There was a significant reduction in the risk of recurrent VTE in favour of LMWH treatment over OAT. Patients treated with LMWH do not seem to have more frequent recurrent VTE events than patients treated with OAT, even after cessation of therapy. The evidence of benefit of LMWH over OAT came mostly from studies that included cancer patients.

CRD commentary

This review addressed a clear research question. The inclusion criteria were clear with regards to the study design and intervention, outcomes and patient characteristics. The authors searched four relevant databases but appeared to exclude any non-English papers that were found, which might have introduced

language bias. The authors also attempted to identify some unpublished material by searching conference abstracts. Two reviewers independently selected the studies and extracted the data, which helps minimise errors and reviewer bias. Publication bias was also assessed and heterogeneity between the studies was investigated. Aspects of validity of the primary studies were assessed but, since the results of the assessment were not explicitly used in the analysis, the strength of the primary studies could not be ascertained. The authors' conclusions may be slightly strong when taking into account the possibility of bias in this review.

Implications of the review for practice and research

The authors did not state any implications for practice or further research.

Bibliographic details

Ferretti G, Bria E, Giannarelli D, Carlini P, Felici A, Mandala M, Papaldo P, Fabi A, Ciccarese M, Cuppone F, Cecere FL, Nuzzo C, Terzoli E, Cognetti F. Is recurrent venous thromboembolism after therapy reduced by low-molecular-weight heparin compared with oral anticoagulants? Chest 2006; 130(6): 1808-1816. [PubMed: 17167001]

Indexing Status

Subject indexing assigned by NLM

MeSH

Anticoagulants /administration & dosage /adverse effects; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Heparin, Low-Molecular-Weight /administration & dosage /adverse effects; Humans; Long-Term Care; Pulmonary Embolism prevention & control; Randomized Controlled Trials as Topic; Recurrence /prevention & control; Substance Withdrawal Syndrome /prevention & control; Venous Thrombosis /prevention & control; Vitamin K /antagonists & inhibitors

AccessionNumber

12007000277

Database entry date

09/08/2008

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: 17167001

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