1.
Meta-analysis to assess the quality of international normalized ratio control and associated outcomes in venous thromboembolism patients.
Mearns, ES, Kohn, CG, Song, JS, Hawthorne, J, Meng, J, White, CM, Raut, MK, Schein, JR, Coleman, CI
Thrombosis research. 2014;(2):310-9
Abstract
INTRODUCTION Patients with venous thromboembolism (VTE) frequently require vitamin K antagonists (VKAs) to prevent recurrent events, but their use increases hemorrhage risk. We performed a meta-analysis to assess the quality of international normalized ratio (INR) control, identify study-level predictors of poor control and to examine the relationship between INR control and adverse outcomes in VTE patients. MATERIALS AND METHODS We searched bibliographic databases (1990-June 2013) for studies of VTE patients receiving adjusted-dose VKAs that reported time in range (2.0-3.0) or proportion of INRs in range and/or reported INR measurements coinciding with thromboembolic or hemorrhagic events. Meta-analysis and meta-regression analysis was performed. RESULTS Upon meta-analysis, studies found 59% (95%CI: 54-64%) of INRs measured and 61% (95%CI: 59-63%) of the time patients were treated were spent outside the target range of 2.0-3.0; with a tendency for under- versus over-anticoagulation. Moreover, this poor INR control resulted in a greater chance of recurrent VTE (beta-coefficient=-0.46, p=0.01) and major bleeding (beta-coefficient=-0.30, p=0.02). Patients with an INR<2.0 made up 58% (95%CI: 39-77%) of VTE cases, while those with an INR>3.0 made up 48% (95%CI: 34-61%) of major hemorrhage cases. Upon meta-regression, being VKA-naïve (-14%, p=0.04) and treated in the community (-7%, p<0.001) were associated with less time in range, while being treated in Europe/United Kingdom (compared to North America) was associated with (11%, p=0.003) greater time. CONCLUSIONS Strategies to improve INR control or alternative anticoagulants, including the newer oral agents, should be widely implemented in VTE patients to reduce the rate of recurrent events and bleeding.
2.
Measures of vitamin K antagonist control reported in atrial fibrillation and venous thromboembolism studies: a systematic review.
Mearns, ES, Hawthorne, J, Song, JS, Coleman, CI
BMJ open. 2014;(6):e005379
Abstract
OBJECTIVE To aid trialists, systematic reviewers and others, we evaluated the degree of standardisation of control measure reporting that has occurred in atrial fibrillation (AF) and venous thromboembolism (VTE) studies since 2000; and attempted to determine whether the prior recommendation of reporting ≥2 measures per study has been employed. DESIGN Systematic review. SEARCH STRATEGY We searched bibliographic databases (2000 to June 2013) to identify AF and VTE studies evaluating dose-adjusted vitamin K antagonists (VKAs) and reporting ≥1 control measure. The types of measures reported, proportion of studies reporting ≥2 measures and mean (±SD) number of measures per study were determined for all studies and compared between subgroups. DATA EXTRACTION Through the use of a standardised data extraction tool, we independently extracted all data, with disagreements resolved by a separate investigator. RESULTS 148 studies were included, 57% of which reported ≥2 control measures (mean/study=2.13±1.36). The proportion of time spent in the target international normalised ratio range (TTR) was most commonly reported (79%), and was frequently accompanied by time above/below range (52%). AF studies more frequently reported ≥2 control measures compared with VTE studies (63% vs 37%; p=0.004), and reported a greater number of measures per study (mean=2.36 vs 1.53; p<0.001). Observational studies were more likely to provide ≥2 measures compared with randomised trials (76% vs 33%; p<0.001) and report a greater number of measures (mean=2.58 vs 1.63; p<0.001). More recent studies (2004-2013) reported ≥2 measures more often than older (2000-2003) studies (59% vs 35%; p=0.05) and reported more measures per study (mean=2.23 vs 1.48; p=0.02). CONCLUSIONS While TTR was often utilised, studies reported ≥2 measures of VKA control only about half of the time and lacked consistency in the types of measures reported. A trend towards studies reporting greater numbers of VKA control measures over time was observed over our review time horizon, particularly, with AF and observational studies.