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Rivaroxaban (Xarelto): Treatment of Venous Thromboembolic Events (Deep Vein Thrombosis [DVT], Pulmonary Embolism [PE]) and Prevention of Recurrent DVT and PE [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2015 Aug.

2OBJECTIVES AND METHODS

2.1. Objectives

To perform a systematic review of the beneficial and harmful effects of rivaroxaban 15 mg and 20 mg for the treatment of pulmonary embolism and/or DVT.

2.2. Methods

Studies were selected for inclusion in the systematic review based on the selection criteria presented in Table 2.

Supplemental Issues

  • Evaluation of the non-inferiority margin (NIM) used in the EINSTEIN PE trial
  • Summary of EINSTEIN DVT extension trial

The literature search was performed by an information specialist using a peer-reviewed literature search strategy.

Published literature was identified by searching the following bibliographic databases: MEDLINE (1946–) with in-process records and daily updates via Ovid; Embase (1974–) via Ovid; and PubMed. The search strategy consisted of both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings (MeSH), and keywords. The main search concepts were Xarelto, rivaroxaban, venous thromboembolism, DVT, and PE.

No methodological filters were applied to limit retrieval by publication type. Where possible, retrieval was limited to the human population. Retrieval was not limited by publication year or by language. Conference abstracts were excluded from the search results.

The initial search was completed on June 12, 2013. Regular alerts were established to update the search until the meeting of the Canadian Drug Expert Committee on October 16, 2013. Regular search updates were performed on databases that do not provide alert services.

Grey literature (literature that is not commercially published) was identified by searching relevant sections of the CADTH Grey Matters checklist (http://www.cadth.ca/en/resources/finding-evidence-is/grey-matters), which includes the websites of regulatory agencies, health technology assessment agencies, clinical trial registries, and professional associations. Google and other Internet search engines were used to search for additional web-based materials. These searches were supplemented by reviewing the bibliographies of key papers and through contacts with appropriate experts. In addition, the manufacturer of the drug was contacted for information regarding unpublished studies.

Two CADTH Common Drug Review (CDR) clinical reviewers independently selected studies for inclusion in the review based on titles and abstracts, according to the predetermined protocol. Full-text articles of all citations considered potentially relevant by at least one reviewer were acquired. Reviewers independently made the final selection of studies to be included in the review, and differences were resolved through discussion. Included studies are presented in Table 3; excluded studies (with reasons) are presented in Appendix 3.

Tables

Table 2Inclusion Criteria For The Systematic Review

Patient PopulationPatients with confirmed PE and/or DVT

Subgroups:
  • intended treatment duration
  • cancer versus non-cancer status
  • age
  • renal function
InterventionRivaroxaban 15 mg b.i.d. for the first three weeks and 20 mg q.d. thereafter for at least 3 months
ComparatorsHeparinsa plus VKA
Fondaparinux plus VKA
LMWH alone
OutcomesKey efficacy outcomes:
Survival rate
Recurrent PE and or DVT
Quality of life
Length of hospitalization
Post-thrombotic syndrome
Degree of pulmonary reperfusion
Pulmonary hypertension

Harms outcomes:
SAEs, WDAEs, and AEs

Adverse events of interest:
Bleeding (major and minor), and hospitalization due to bleeding
Heparin-induced thrombocytopenia
Liver function
Study DesignPublished and unpublished RCTs

AE = adverse event; b.i.d. = twice daily; q.d. = once daily; RCT = randomized controlled trial; SAE = serious adverse event; WDAE = withdrawal due to adverse event.

a

Unfractionated heparin (intravenously or subcutaneously administered) or low-molecular-weight heparin.

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Bookshelf ID: NBK344337
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