Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic review and meta-analysis.

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Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic review and meta-analysis.

CMAJ. 2008 Jul 29;179(3):235-44

Authors: Oake N, Jennings A, Forster AJ, Fergusson D, Doucette S, van Walraven C

BACKGROUND: Patients taking oral anticoagulant therapy balance the risks of hemorrhage and thromboembolism. We sought to determine the association between anticoagulation intensity and the risk of hemorrhagic and thromboembolic events. We also sought to determine how under-or overanticoagulation would influence patient outcomes. METHODS: We reviewed the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL databases to identify studies involving patients taking anticoagulants that reported person-years of observation and the number of hemorrhages or thromboemboli in 3 or more discrete ranges of international normalized ratios. We estimated the overall relative and absolute risks of events specific to anticoagulation intensity. RESULTS: We included 19 studies. The risk of hemorrhage increased significantly at high international normalized ratios. Compared with the therapeutic ratio of 2-3, the relative risk (RR) of hemorrhage (and 95% confidence intervals [CIs]) were 2.7 (1.8-3.9; p < 0.01) at a ratio of 3-5 and 21.8 (12.1-39.4; p < 0.01) at a ratio greater than 5. The risk of thromboemboli increased significantly at ratios less than 2, with a relative risk of 3.5 (95% CI 2.8-4.4; p < 0.01). The risk of hemorrhagic or thromboembolic events was lower at ratios of 3-5 (RR 1.8, 95% CI 1.2-2.6) than at ratios of less than 2 (RR 2.4, 95% CI 1.9-3.1; p = 0.10). We found that a ratio of 2-3 had the lowest absolute risk (AR) of events (AR 4.3%/yr, 95% CI 3.0%-6.3%). Conclusions: The risks of hemorrhage and thromboemboli are minimized at international normalized ratios of 2-3. Ratios that are moderately higher than this therapeutic range appear safe and more effective than subtherapeutic ratios.

PMID: 18663203 [PubMed - indexed for MEDLINE]

One Comment

  1. The target INR for warfarin therapy for non-valve-related thromboprophylaxis is generally 2-3, although this target is occasionally adjusted upward for patients with high thromboembolic risk and downward for patients with high bleeding risk. Interestingly, this meta-analysis does not support such a practice. A target INR of less than 2 was not associated with a statistically significant reduction in hemorrhagic risk relative to a target of 2-3 (RR 1.1 for <2 vs 1.0 for 2-3). A target INR of 3-5 was not associated with a statistically significant reduction in thromboembolic risk relative to a target INR of 2-3 (RR 0.9 for 3-5 vs 1.0 for 2-3). Bleeding risks increased significantly for INR > 3 and thromboembolic risk increased significantly for INR < 2. The large standard error in this study suggests that the numbers were not adequate to detect small differences. However, this meta-analysis suggests that there is little benefit in non-valve thromboprophylaxis to aim for target INR's outside the 2-3 range.

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