Chest

Chest

Volume 129, Issue 5, May 2006, Pages 1155-1166
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Original Research: Anticoagulation
Effect of Study Setting on Anticoagulation Control: A Systematic Review and Metaregression

https://doi.org/10.1378/chest.129.5.1155Get rights and content

Background

For patients receiving therapy with oral anticoagulants (OACs), the proportion of time spent in the therapeutic range (ie, anticoagulation control) is strongly associated with bleeding and thromboembolic risk. The effect of study-level factors, especially study setting, on anticoagulation control is unknown.

Objectives

Describe anticoagulation control achieved in the published literature. We also used metaregressive techniques to determine which study-level factors significantly influenced anticoagulation control.

Studies

All published randomized or cohort studies that measured international normalized ratios (INRs) serially in anticoagulated patients and reported the proportion of time between INRs ranging from 1.8 to 2.0 and 3.0 to 3.5.

Results

We identified 67 studies with 123 patient groups having 50,208 patients followed for a total of 57,154.7 patient-years. A total of 68.3% of groups were from anticoagulation clinics, 7.3% were from clinical trials, and 24.4% were from community practices. Overall, patients were therapeutic 63.6% of time (95% confidence interval [CI], 61.6 to 65.6). In the metaregression model, study setting had the greatest effect on anticoagulation control with studies in community practices having significantly lower control than either anticoagulation clinics or clinical trials (−12.2%; 95% CI, −19.5 to −4.8; p < 0.0001). Self-management was associated with a significant improvement of time spent in the therapeutic range (+7.0%; 95% CI, 0.7 to 13.3; p = 0.03).

Conclusions

Patients who have received anticoagulation therapy spend a significant proportion of their time with an INR out of the therapeutic range. Patients from community practices showed significantly worse anticoagulation control than those from anticoagulation clinics or clinical trials. This should be considered when interpreting the results of, and generalizing from, studies involving OACs.

Section snippets

Search Strategy and Study Inclusion Criteria

We searched the MEDLINE database using the search strategy shown in Appendix 1. The rest of our search strategy, along with its outcome, is illustrated in Figure 1. Studies were included if they contained original data measuring anticoagulation control in at least one patient group over time. This required the calculation of serial INRs on each person and an interpolation of the values between actual measures so that anticoagulation status could be determined on each day of observation. We

Results

The MEDLINE search retrieved 1,835 citations (Appendix 1), of which 190 appeared to study anticoagulation monitoring (Fig 1). A total of 79 of these articles studied anticoagulation control using a patient-time approach. We identified a further 39 articles from alternative sources including Embase (n = 8), Web of Science (n = 13), and hand searching (n = 18). Of the resulting 118 articles, we excluded 51 because the INR measures were not used to assess anticoagulation (n = 7), a target INR

Discussion

To our knowledge, this is the first systematic review and metaregression of studies measuring anticoagulation control. We found a large number of studies that used a patient-time approach to measure the percentage of time in a typical therapeutic target range. The overall percentage of time spent in the therapeutic range was 63.5% (95% CI, 61.6 to 65.6%). However, anticoagulation control varied extensively among study groups, with study setting, drug type, and self-monitoring being the most

Appendix 1: medline research strategy for study

  • 1

    acenocoumarol.mp. or ACENOCOUMAROL/ (825)

  • 2

    dicumarol.mp. or DICUMAROL/ (1310)

  • 3

    ethyl biscoumacetate.mp. or Ethyl Biscoumacetate/ (163)

  • 4

    phenprocoumon.mp. or PHENPROCOUMON/ (705)

  • 5

    Warfarin.mp. or WARFARIN/ (11151)

  • 6

    ADMINISTRATION, ORAL/or oral.mp. (301044)

  • 7

    1 or 2 or 3 or 4 or 5 or 6 (312429)

  • 8

    *ANTICOAGULANTS/ (15843)

  • 9

    INR.mp. or International Normalized Ratio/ (2675)

  • 10

    international normalized ratio.mp. (2104)

  • 11

    9 or 10 (3108)

  • 12

    prothrombin time.mp. or Prothrombin Time/ (9487)

  • 13

    PT.mp. (12621)

  • 14

    PTR.mp. (340)

  • 15

    12 or 13 or 14

Acknowledgment

We thank Steve Doucette for his help with the analyses and Dr. Phillip Wells for reviewing previous drafts of this study.

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    This study was supported in part by Institute for Safe Medication Practices Canada. Dr. Forster was an Ontario Ministry of Health Career Scientist when this study was conducted. No authors have conflicts of interest to disclose.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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    Copyright © 2006 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.