Anne Holbrook, MD, PharmD
What is the effect of anticoagulation intensity on risk for thromboembolism or hemorrhage in patients taking oral anticoagulants (OAs)?
Studies selected evaluated OA therapy for various indications and reported the number of outcome events and corresponding person-years of observation for ≥ 3 discrete ranges of international normalized ratios (INRs) (< 2, 2 to 3, and > 3). Patients taking both antiplatelet and anticoagulant medications were excluded. Outcomes were thromboembolism and hemorrhage; if severity of events was reported, those of minor severity were not included.
MEDLINE, EMBASE/Excerpta Medica, CINAHL, and Cochrane Central Register of Controlled Trials (all to 2006), and Science Citation Index were searched for studies. 19 studies (n = 80 713, 56% men, mean follow-up 0.2 to 4.6 y) met the selection criteria: 10 retrospective cohort studies, 3 prospective cohort studies, and 6 randomized controlled trials (RCTs). 17 studies reported hemorrhagic events, including those that required hospitalization, blood transfusion, or surgery, or were intracranial or fatal; 16 reported thromboembolic events, including stroke, myocardial infarction, and systemic emboli. The meta-analysis compared outcomes by achieved INR ranges (reference INR range 2 to 3).
There were 98 900 patient-years of follow-up across all trials. Meta-analysis showed that anticoagulation with INRs > 3 increased risk for hemorrhage and anticoagulation with INRs < 2 or > 5 increased risk for thromboembolism (Table). When hemorrhage and thromboembolism were combined, anticoagulation with INRs < 2, between 3 and 5, and > 5 increased risk compared with the reference range (2 to 3) (Table). Significant heterogeneity between studies was detected.
In patients taking oral anticoagulants, anticoagulation with international normalized ratios < 2 or between 3 and 5 increases risk for hemorrhage or thromboembolism compared with a reference range of 2 to 3.
Anticoagulation with achieved international normalized ratios (INRs) in patients taking oral anticoagulants*
*Abbreviations defined in Glossary.
Holbrook A. Review: Anticoagulation with INRs < 2 or between 3 and 5 increases risk for thromboembolic or hemorrhagic events. Ann Intern Med. 2008;149:JC5–5. doi: 10.7326/0003-4819-149-10-200811180-02005
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Published: Ann Intern Med. 2008;149(10):JC5-5.
Coagulopathies, Hematology/Oncology, Venous Thromboembolism.
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