Frequency of adverse events in patients with poor anticoagulation: a meta-analysis

Abstract

DOI:P atients taking anticoagulants orally over the long term have international normalized ratios (INRs) that fall outside the individual therapeutic range more than one-third of the time.1 Improved anticoagulation control reduces hemorrhagic and thromboembolic event rates. 2,3 Many studies have shown that such event rates are higher when patients' INRs are outside the therapeutic range.4-11 A study that systematically measures the proportion of hemorrhages and thromboemboli that occur when INRs are above and below the therapeutic range, respectively, will help both physicians and policy-makers gauge the potential effect of improved anticoagulation control. In our investigation, we measured and analyzed these proportions. MethodsWe identified pertinent citations in English in the MEDLINE and EMBASE (1980EMBASE ( -2006 databases using the search strategy outlined in Appendix 1. This strategy combined medical subject headings and keywords related to anticoagulation (e.g., anticoagulants, warfarin) and to hemorrhages and thromboemboli (e.g., cerebrovascular accident, bleed). We retrieved the full text of articles for further review if the title or abstract suggested that patients taking anticoagulants were studied and data on hemorrhages or thromboemboli were reported. Studies were included in our review if the majority of patients taking anticoagulants orally had an INR range with a lower limit between 1.8 and 2 and an upper limit between 3 and 3.5, and the INR at the time of the hemorrhagic or thromboembolic event was recorded; these limits represent the most common therapeutic ranges for patients taking oral anticoagulants. All citations and studies were reviewed for inclusion by a single author (N.O.). We considered all major hemorrhages (i.e., those that required hospital admission, a transfusion or surgery, or that reduced hemoglobin levels by ≥ 20 g/L) and thromboemboli (stroke, myocardial infarction, venous thromboembolism or systemic emboli, confirmed by objective tests). We excluded patient groups taking anticoagulants by mouth with concomitant antiplatelet therapy, because their risk of hemorrhagic and thromboembolic events is considerably higher than the risks of patients taking anticoagulants alone. 12,13From each study, we abstracted the total number of major hemorrhages and thromboemboli that could be assigned to particular INR ranges. Some studies assigned events to INRs based on measurements taken at the time of the event or at hospital admission, whereas others used measurements made beforehand to approximate the INR at the time of the event. We grouped the events into 3 INR ranges: below, DOI:10.1503/cmaj.061523 Natalie Oake, Dean A. Fergusson, Alan J. Forster, Carl van Walraven Frequency of adverse events in patients with poor anticoagulation: a meta-analysis Background: Patients taking anticoagulants orally over the long term have international normalized ratios (INRs) outside the individual therapeutic range more than one-third of the time. Improved anticoagulation control will reduce hem...

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