1.
Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States.
Baker, WL, Cios, DA, Sander, SD, Coleman, CI
Journal of managed care pharmacy : JMCP. 2009;(3):244-52
Abstract
BACKGROUND Atrial fibrillation (AF) affects a significant proportion of the American population and increases ischemic stroke risk by 4- to 5-fold. Oral vitamin K antagonists, such as warfarin, can significantly reduce this stroke risk but can be difficult to dose and monitor. Previous research on the effects of setting (e.g., randomized controlled trials, anticoagulation management by specialty clinics, usual care by community physicians) on the proportion of time spent within therapeutic range for the international normalized ratio (INR) has not specifically examined anticoagulation in AF patients. OBJECTIVES Use traditional meta-analytic and meta-regressive techniques to evaluate the effect of specialty clinic versus usual care by community physicians on anticoagulation control, measured as the proportion of time spent in therapeutic INR range, for AF patients that received warfarin anticoagulation in the United States. METHODS Studies included in a previously published meta-analysis (van Walraven et al., 2006), which systematically searched reports between 1987 and 2005, were also screened for inclusion in our analysis. A subsequent systematic literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Clinical Trials from January 2005 through February 2008 was conducted. Studies were included if they (a) contained at least 1 warfarin-treated group including more than 25 patients for whom INR control was monitored for at least 3 weeks; (b) included patients treated for AF in the United States; (c) used a patient-time approach (patient-year) to report outcomes; and (d) reported data on the proportion of time spent in traditional therapeutic INR ranges (i.e., a lower limit INR between 1.8 and 2.0 and an upper limit INR between 3.0 and 3.5. Studies with INR goals outside this range were excluded). The proportion of time spent within the therapeutic INR range for each study group was expressed as an incidence density using a person-time approach (in years). All studies were pooled using a random effects model and were weighted by the inverse of the variance of proportion of time spent in the therapeutic range. In order to determine how study setting influenced the proportion of time spent within a therapeutic INR range, both subgroup and meta-regression analyses were conducted. RESULTS This analysis included 8 studies and a total of 14 unique warfarin- treated groups; 3 of the 8 studies and 4 of the warfarin groups were not included in the previous meta-analysis (van Walraven et al., 2006). Overall, patients spent a mean 55% (95% CI = 51%-58%) of their time in the therapeutic INR range. Meta-regression suggested that AF patients treated in a community usual care setting compared with an anticoagulation clinic spent 11% (95% CI = 2%-20%, n = 6 studies with 9 study groups) less time in range. CONCLUSIONS In the United States, AF patients spend only about one-half the time within therapeutic INR. Anticoagulation clinic services are associated with somewhat better INR control compared with standard community care.
2.
Individual patient meta-analysis of self-monitoring of an oral anticoagulation protocol.
Perera, R, Heneghan, C, Fitzmaurice, D, ,
The Journal of heart valve disease. 2008;(2):233-8
Abstract
BACKGROUND AND AIM OF THE STUDY Oral anticoagulation with vitamin K antagonists is effective for the prevention and treatment of thromboembolic events. Recent systematic reviews have shown that self-monitoring improved the quality of oral anticoagulation therapy (OAT), with patients spending more time in the therapeutic range than traditionally monitored patients, and with a concomitant decrease in the incidence of adverse effects. However, methodological and reporting heterogeneity has limited the strength of the reviews' conclusions. Differences were noted in terms of the assessment of outcome measures and the analysis methods used. For instance, not all used an intention-to-treat analysis, which may have over-inflated the results. Interpretation was limited by missing data: for example, it was not possible to combine mean tests in range, mean time in range, or to determine the level of deviant values. Time-to-event data (e.g., death, thromboembolic events) were reported as numbers of events, which prevented adequate analysis. In order to overcome these limitations and allow further investigation of the data, the study aim is to undertake an Individual Patient Data (IPD) meta-analysis. METHODS AND STUDY DESIGN The IPD analysis will include data from randomized trials that have compared self-monitoring (self-testing or self-management) OAT versus a control group, and that measured adverse events defined as major hemorrhage, thromboembolism, and death. The data to be requested for each trial will include: outcomes, demographic and psychosocial (e.g., quality of life) data. The primary outcomes of interest will be time to major hemorrhage, thromboembolism, and death. The secondary outcomes will be minor hemorrhage, percentage time within range, percentage tests within range, and patient satisfaction. The primary analysis will be by intention to treat, and multilevel models with patients and trials as the two levels, will be explored to investigate treatment effects on various outcomes. Patient-level covariates will be incorporated into the models in an attempt to account for statistical heterogeneity, as well as to investigate interactions with treatment effect. CONCLUSION Predictive models should lead to the identification of those most likely to benefit from self-monitoring of oral anticoagulation, and potentially also to a targeted and a more cost-effective use of the intervention.