Factors influencing dabigatran or warfarin medication persistence in patients with nonvalvular atrial fibrillation.

Factors influencing differences in persistence between dabigatran and warfarin in patients with nonvalvular atrial fibrillation (NVAF) remain unclear. AIM: Compare differences in persistence between new dabigatran and warfarin users in patients newly diagnosed with NVAF, adjusting for sociodemographics, clinical characteristics, patient out-of-pocket cost and other covariates. METHODS: A retrospective matched-cohort study was conducted using a US claims database of Medicare and commercially insured patients with NVAF aged≥ 18 years. Persistence and monthly out-of-pocket costs for dabigatran or warfarin were calculated and adjusted for covariates using Cox proportional hazard models. RESULTS & CONCLUSION: Unadjusted persistence was significantly lower among dabigatran users (n = 1025) compared with matched warfarin users (38 vs 46%). Adjusting for covariates rendered this difference insignificant (hazard ratio = 0.930).

The cost of cardiovascular-disease-related death in patients with type 2 diabetes mellitus.

OBJECTIVES: To assess the magnitude of difference in all-cause healthcare resource utilization (HCRU) and costs between patients with type 2 diabetes mellitus (T2DM) who died from a cardiovascular disease (CVD)-related cause in the year preceding death vs. those who did not die during this same period. METHODS: A large US administrative claims database was used to identify patients with T2DM who died of a CVD-related cause from July 2012 to April 2015. These patients were matched 1:1 to patients with T2DM who did not die, using direct matching methods. HCRU and costs were assessed in each of the four quarters (Q4: 12-10 months; Q3: 9-7 months; Q2: 6-4 months; and Q1: 3-0 months) prior to death and compared between patient cohorts using paired t-tests and McNemar's tests. RESULTS: A final matched cohort of 7648 patients who died and 7648 patients who did not die were identified. A significantly higher proportion of patients who died utilized inpatient services vs. those who did not die (Q4: 12.6% vs. 4.6%, p < .001; Q3: 14.6% vs. 4.6%, p < .001; Q2: 17.6% vs. 5.5%, p < .001; and Q1: 65.0% vs. 10.1%, p < .001). In addition, patients who died incurred significantly higher all-cause costs (Q4: $8882 vs. $3970, p < .001; Q3: $10,462 vs. $3661, p < .001; Q2: $12,564 vs. $4169, p < .001; and Q1: $36,076 vs. $6319, p < .001). CONCLUSIONS: T2DM patients with a CVD-related death had significantly greater HCRU and costs in the year including and preceding death compared to those who did not die.

Incremental burden of type 2 diabetes in patients experiencing cardiovascular hospitalizations.

OBJECTIVE: To evaluate the incremental economic burden of type 2 diabetes in patients experiencing cardiovascular (CV) hospitalizations. RESEARCH DESIGN AND METHODS: Adults with ≥1 CV hospitalization were identified using a US-based healthcare claims database from 1 July 2011 to 30 June 2014. Outcomes for patients surviving the index hospitalization were compared between patients with vs. without type 2 diabetes (cohorts were identified in the pre-index period). Subsequent CV hospitalizations were evaluated using Cox proportional hazards models. All-cause and CV-related healthcare resource utilization (HCRU) and costs captured on a per-patient per-month (PPPM) basis during a variable follow-up period were evaluated using appropriate multivariable regression models. RESULTS: Of 316,207 patients with ≥1 CV hospitalization, 23% had comorbid type 2 diabetes. The mean age ± SD was 62.6 ± 12.3 years and 64.4% were male. During follow-up, the type 2 diabetes cohort had a 19% higher risk of subsequent CV hospitalizations compared to the non-type-2-diabetes cohort (p < .001). This difference in risk was highest in patients aged 35-44 years. Subsequent all-cause hospitalizations for the type 2 diabetes cohort were longer (mean length of stay, 6.7 vs. 6.3 days; p < .001), with higher total bed-days PPPM (mean, 0.52 vs. 0.43; p < .001), compared to the non-type-2-diabetes cohort. The type 2 diabetes cohort had a significantly higher incremental cost for both the index CV hospitalization (mean cost difference, $1046; p < .001) and all-cause costs PPPM following discharge (mean cost difference, $749; p < .001). CONCLUSIONS: Comorbid type 2 diabetes was associated with an increased risk of subsequent CV hospitalizations and higher costs and HCRU during the follow-up period.

Health Care Resource Utilization and Costs Among Newly Diagnosed and Oral Anticoagulant-Naive Nonvalvular Atrial Fibrillation Patients Treated with Dabigatran or Warfarin in the United States.

BACKGROUND: Warfarin has a long history of use to reduce the risk of stroke in patients with atrial fibrillation (AF), but it requires frequent laboratory monitoring to maintain international normalized ratio levels in the therapeutic range. Dabigatran, a novel oral anticoagulant (OAC), has demonstrated efficacy in reducing the risk of stroke and systemic embolism and does not require laboratory monitoring. OBJECTIVE: To compare health care resource utilization (HCRU) and costs of OAC-naive patients newly diagnosed with nonvalvular atrial fibrillation (NVAF), using dabigatran or warfarin. METHODS: This retrospective observational study used data from medical and pharmacy claims extracted from the HealthCore Integrated Research Database representing commercial and Medicare Advantage members. Adults aged > 18 years with a medical diagnosis claim of NVAF were identified between October 1, 2010, and December 31, 2011. The date of first observed OAC prescription claim was the index date. Patients were followed for up to 12 months after the index date. Patients were assigned to the dabigatran or warfarin treatment groups based on their first OAC prescription fills. To reduce potential for selection bias, the cohorts were matched on baseline characteristics using propensity score matching. HCRU was measured and compared between groups on a per-patient-per-month (PPPM) basis for all-cause HCRU, as well as stroke, myocardial infarction, and bleed-specific HCRU. Pharmacy, medical, and total costs were also compared and adjusted to 2012 U.S. dollars. Generalized linear models were conducted to compare all-cause health care costs between cohorts. RESULTS: After propensity score matching, 1,648 patients were included in the analysis (824 each in the dabigatran and warfarin treatment groups). In the post-index period, patients in the dabigatran group had significantly fewer all-cause PPPM physician office visits (mean [SD] 1.29 [± 0.95] vs. 2.02 [± 1.53], P < 0.001) and outpatient visits (mean [SD] 2.17 [± 2.90] vs. 3.52 [± 3.32], P < 0.001) compared with those in the warfarin group. There were no between-group differences in outcomes for the number of stroke, myocardial infarction, or bleeding-related office visits. All-cause medical costs for the dabigatran cohort were lower than the warfarin cohort; however, the difference did not reach statistical significance ($2,696 [SD ± $6,699] vs. $2,893 [± $6,819], P = 0.179). All-cause pharmacy costs were higher in the dabigatran group versus the warfarin group ($455 [± $429] vs. $328 [± $517], P < 0.001). The dabigatran cohort also had significantly higher stroke-related ($32 [± $71] vs. $20 [± $55], P = 0.006) and nonstroke-related pharmacy costs ($423 [± $422] vs. $308 [± $515], P < 0.001). Despite higher pharmacy costs for the dabigatran cohort, both treatment groups had statistically similar all-cause total costs ($3,151 [± $6,744] vs. $3,221 [± $6,869], P = 0.701). CONCLUSIONS: This real-world study showed that among patients newly diagnosed with NVAF who were OAC naive, dabigatran use was associated with significantly less HCRU in terms of physician and outpatient visits but higher pharmaceutical costs in up to 12 months of follow-up. Similar to other real-world studies, this research supports the finding that higher pharmacy costs for dabigatran users was offset by lower medical costs, making total health care costs comparable between dabigatran and warfarin. DISCLOSURES: This work was supported by Boehringer Ingelheim Pharmaceuticals, which is the manufacturer of dabigatran, one of the products included in the analysis of this work. The authors were responsible for all content and editorial decisions. Jain and Tan are employed by HealthCore, a research consultancy which was funded by Boehringer Ingelheim Pharmaceuticals for work on this study. Fu was employed by HealthCore at the time of this study. Lim, Wang, Elder, and Sander are employees of Boehringer Ingelheim Pharmaceuticals. Study concept and design were contributed by Wang, Sander, and Tan, along with Fu and Jain. Fu, Tan, and Jain collected the data, and data interpretation was performed by Lim, Wang, and Sander, along with Jain, Tan, and Fu. The manuscript was written by Jain, Elder, Tan, and Wang, along with Lim and Fu, and revised by Jain, Wang, Elder, and Tan. Some of the results of this study were presented at Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke (QCOR) 2014 Scientific Sessions on June 2-4, 2014, in Baltimore, Maryland.

Health Care Resource Utilization, Costs, and Persistence in Patients Newly Diagnosed as Having Nonvalvular Atrial Fibrillation and Newly Treated With Dabigatran versus Warfarin in the United States.

PURPOSE: This study compared health care resource utilization (HCRU), costs, and persistence among patients newly diagnosed as having nonvalvular atrial fibrillation (NVAF) and newly treated with dabigatran versus warfarin. METHODS: This retrospective claims-based study used data from a large US managed care organization. The earliest claim for dabigatran or warfarin during October 1, 2010 through October 31, 2011 was the index date, with cohort assignment based on index medication. Evidence of newly diagnosed NVAF within 30 days before the index date and no claims for oral anticoagulants during the 12-month preindex period were required. Cohorts were matched using propensity scores. Per-patient-per-month HCRU, costs, and persistence were calculated during the variable follow-up period of up to 12 months after the index date. Descriptive and multivariable analyses were used to examine differences in outcomes. FINDINGS: After matching, 869 patients per cohort were identified (mean age, 67.8 years; 40.4% female). Compared with warfarin, dabigatran had fewer per-patient-per-month emergency department (0.10 vs 0.13, P = 0.010), office (1.98 vs 2.96, P < 0.001), and outpatient (1.05 vs 1.48, P < 0.001) visits. Despite higher mean pharmacy costs for dabigatran (P < 0.001), mean total health care (P = 0.309) and medical costs (P = 0.568) were similar to warfarin. Persistence was higher with dabigatran versus warfarin (median, 204 vs 161 days; mean, 213.7 vs 195.5 days, P = 0.001). IMPLICATIONS: Among patients newly diagnosed as having NVAF, those newly treated with dabigatran had lower HCRU, higher persistence, and similar total health care costs compared with those treated with warfarin.

Hospital Admissions, Costs, and 30-Day Readmissions Among Newly Diagnosed Nonvalvular Atrial Fibrillation Patients Treated with Dabigatran Etexilate or Warfarin.

BACKGROUND: Oral anticoagulation such as warfarin and dabigatran is indicated for atrial fibrillation (AF) patients at risk of ischemic stroke. Dabigatran etexilate was developed to address the limitations of warfarin, including the need for regular blood monitoring, which has the potential to lead to higher health care resource use, particularly in hospitalized patients. OBJECTIVE: To evaluate whether hospitalization cost, length of hospital stay (LOS), likelihood of readmission within 30 days, and cost of readmissions differed across inpatient encounters among nonvalvular atrial fibrillation (NVAF) patients that were newly diagnosed and newly treated with either dabigatran or warfarin. METHODS: A retrospective cohort study was conducted using IMS Health's Charge Detail Master (CDM) database. Hospitalizations were identified based on a primary or secondary AF diagnosis, dabigatran or warfarin use, and a discharge date from January 2011 through March 2012. The identified patients without valvular procedures and transient AF were required to have a minimum of 12 months of pharmacy and private practitioner records prior to the inpatient encounter to ensure that they were newly treated on dabigatran or warfarin. Propensity score matching was used to balance baseline characteristics between treatment cohorts. Outcomes assessed were LOS, 30-day readmissions, and costs. Because individual patients could have more than 1 hospital observation, generalized estimating equations (GEE) with a gamma distribution (log link) were used for the analysis of continuous outcome measures (e.g., LOS and costs) and a binominal distribution for dichotomous outcomes (hospital readmissions). RESULTS: Two cohorts were propensity score matched (1:2) on demographic and clinical characteristics. The dabigatran cohort included 646 hospitalizations, and the warfarin cohort included 1,292 hospitalizations. Hospitalizations were on average 13% shorter (4.8 vs. 5.5 days, P less than 0.001) and cost 12% less ($14,794 vs. $16,826, P = 0.007) when dabigatran was used versus warfarin. No differences in 30-day readmissions were observed. CONCLUSIONS: Hospital encounters among newly diagnosed NVAF patients during which warfarin was initiated had longer lengths of stay and incurred higher costs than those during which dabigatran was initiated.

Long-Term Costs of Ischemic Stroke and Major Bleeding Events among Medicare Patients with Nonvalvular Atrial Fibrillation.

Purpose. Acute healthcare utilization of stroke and bleeding has been previously examined among patients with nonvalvular atrial fibrillation (NVAF). The long-term cost of such outcomes over several years is not well understood. Methods. Using 1999-2009 Medicare medical and enrollment data, we identified incident NVAF patients without history of stroke or bleeding. Patients were followed from the first occurrence of ischemic stroke, major bleeding, or intracranial hemorrhage (ICH) resulting in hospitalization. Those with events were matched with 1-5 NVAF patients without events. Total incremental costs of events were calculated as the difference between costs for patients with events and matched controls for up to 3 years. Results. Among the 25,465 patients who experienced events, 94.5% were successfully matched. In the first year after event, average incremental costs were $32,900 for ischemic stroke, $23,414 for major bleeding, and $47,640 for ICH. At 3 years after these events, costs remained elevated by $3,156-$5,400 per annum. Conclusion. While the costs of stroke and bleeding among patients with NVAF are most dramatic in the first year, utilization remained elevated at 3 years. Cost consequences extend beyond the initial year after these events and should be accounted for when assessing the cost-effectiveness of treatment regimens for stroke prevention.

Patterns and predictors of use of warfarin and other common long-term medications in patients with atrial fibrillation.

BACKGROUND AND OBJECTIVE: No study has been published that compared persistence and discontinuation of warfarin with other long-term medications in patients with atrial fibrillation (AF). The objective of this study was to evaluate persistence and discontinuation patterns in AF patients taking warfarin and other common long-term medications and identify predictors of persistence and discontinuation in this population. METHODS: Patients with warfarin prescription within 3 months after AF hospitalization discharge and 12-month data before and after the first prescription were evaluated using administrative claims data (1 January 2005 - 31 December 2007). For comparison, persistence patterns for other long-term medications for treatment of hypertension, hyperglycemia, heart disease, and dyslipidemia, including once- (od) and twice- (bid) daily medications, were evaluated. Non-persistence was defined as the presence of a ≥60-day gap in medication use. Permanent discontinuation was defined as no use of the medication for ≥90 days until the end of the follow-up period. Multivariate analysis was conducted to identify predictors of warfarin non-persistence and discontinuation. RESULTS: 28 384 patients with AF were identified; 16 036 (56.5%) had a warfarin prescription following AF hospitalization. 53.5% of warfarin users were persistent for at least 1 year, similar to other long-term medications commonly prescribed to the AF population (ranging between 45.2% and 61.3%). 42.6% of warfarin users permanently discontinued warfarin within 1 year, also consistent with the discontinuation rate of 32.9-52.0% of other long-term medications. Residence in the South and West regions of the US, history of cardiac dysrhythmias, and warfarin cost-sharing significantly decreased the likelihood of warfarin persistence and increased the likelihood of discontinuation, while older age, history of ischemic stroke, and warfarin use before hospitalization significantly increased warfarin persistence and decreased the likelihood of discontinuation. Adherence of od and bid medications was similar. CONCLUSION: Persistence and discontinuation with warfarin in patients with AF is consistent with other long-term medications. Identifying factors associated with non-persistence and discontinuation with long-term medications can help in developing targeted adherence programs.

Impact of atrial fibrillation and oral anticoagulation on hospital costs and length of stay.

PURPOSE: The results of a study assessing hospital length of stay (LOS) and inpatient costs associated with nonvalvular atrial fibrillation (AF) and AF-related warfarin use during hospitalization are presented. METHODS: Managed care administrative claims data were used to construct cohorts of patients hospitalized with AF as a primary (n = 1,868) or secondary (n = 11,200) discharge diagnosis and control groups of patients with similar demographics and clinical characteristics who were hospitalized during the same period (2002-07). Multivariate regression analyses were performed to estimate the incremental impact of AF on hospital LOS and costs per admission, as well as the incremental impact of in hospital warfarin use on the evaluated LOS and cost outcomes. RESULTS: The cohort of patients with AF as a secondary discharge diagnosis had a mean LOS 1.84 days greater (p < 0.001) and a mean hospital costs $3,146 higher (p < 0.001) than the control cohort; in hospital warfarin use in those patients was associated with a mean increase in LOS of 1.45 days (p < 0.001) and a mean increase in hospital costs of $1,761 per admission (p < 0.001). In the cohort of patients with AF as a primary discharge diagnosis, inpatient warfarin therapy was also associated with longer hospital stays (mean increase, 1.26 days; p < 0.001) and higher hospital costs (mean increase, $678; p = 0.031). CONCLUSION: Hospitalizations of patients with a secondary diagnosis of AF are significantly longer and more costly than those of patients without a secondary diagnosis of AF, especially when warfarin is used during the hospital stay. Among patients with a primary diagnosis of AF, warfarin therapy during hospitalization is associated with significant increases in mean LOS and hospital costs.

Cost efficiency of anticoagulation with warfarin to prevent stroke in medicare beneficiaries with nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: in controlled trials, anticoagulation with warfarin reduces stroke risk by nearly two thirds, but the benefit has been less pronounced in clinical practice. This report describes the extent of warfarin use, its effectiveness, and its impact on medical costs among Medicare patients with nonvalvular atrial fibrillation. METHODS: using claims from >2 million beneficiaries in the Centers for Medicare and Medicaid Services 5% Sample Standard Analytic Files, we identified patients with nonvalvular atrial fibrillation from 2004 to 2005. Warfarin use was inferred from 3 or more tests of the international normalized ratio within 1 year. Incidence of ischemic/hemorrhagic stroke and major bleeding was evaluated. Adjusted risk was calculated by Cox proportional-hazards regression. Medical costs (reimbursed amounts in 2006 US dollars) were estimated by multivariate linear regression. RESULTS: of patients with nonvalvular atrial fibrillation (N=119 764, mean age=79.3 years), 58.5% were categorized as warfarin users based on the study definition. During an average of 2.1 years' follow-up, the rate of ischemic stroke was 3.9 per 100 patient-years. After multivariate adjustment, ischemic stroke incidence was 27% lower in patients taking warfarin than in patients not taking warfarin (P<0.0001), with no increase in hemorrhagic stroke and a slightly elevated risk of a major bleed. Use of warfarin was independently associated with lower total medical costs, averaging $9836 per patient per year. CONCLUSIONS: these results indicate that 41.5% of Medicare patients with nonvalvular atrial fibrillation are not anticoagulated with warfarin. The incidence of stroke and overall medical costs were significantly lower in patients treated with warfarin.

Costs and outcomes of noncardioembolic ischemic stroke in a managed care population.

PURPOSE: To evaluate the clinical outcomes and incremental health care costs of ischemic stroke in a US managed care population. PATIENTS AND METHODS: A retrospective cohort analysis was done on patients (aged 18+ years) hospitalized with noncardioembolic ischemic stroke from January 1, 2002, through December 31, 2003, identified from commercial health plan administrative claims. New or recurrent stroke was based on history in the previous 12 months, with index date defined as first date of indication of stroke. A control group without stroke or transient ischemic attack (TIA) was matched (1:3) on age, sex, and geographic region, with an index date defined as the first medical claim during the patient identification period. Patients with atrial fibrillation or mitral value abnormalities were excluded. Ischemic stroke and control cohorts were compared on 4-year clinical outcomes and 1-year costs. RESULTS: Of 2180 ischemic stroke patients, 1808 (82.9%) had new stroke and 372 (17.1%) had a recurrent stroke. Stroke patients had higher unadjusted rates of additional stroke, TIA, and fatal outcomes compared with the 6540 matched controls. Recurrent stroke patients had higher rates of adverse clinical outcomes compared with new stroke patients; costs attributed to recurrent stroke were also higher. Stroke patients were 2.4 times more likely to be hospitalized in follow-up compared with controls (hazard ratio [HR] 2.4, 95% confidence interval [CI]: 2.2, 2.6). Occurrence of stroke following discharge was 21 times more likely among patients with index stroke compared with controls (HR 21.0, 95% CI: 16.1, 27.3). Stroke was also predictive of death (HR 1.8, 95% CI: 1.3, 2.5). Controlling for covariates, stroke patients had significantly higher costs compared with control patients in the year following the index event. CONCLUSION: Noncardioembolic ischemic stroke patients had significantly poorer outcomes and higher costs compared with controls. Recurrent stroke appears to contribute substantially to these higher rates of adverse outcomes and costs.

Burden of illness among patients at high risk versus low risk for major cardiovascular events.

OBJECTIVE: This study was designed to compare the burden of illness (BOI) in patients at high risk versus low risk of developing a major cardiovascular (CV) event. METHODS: This retrospective claims data analysis included commercial health plan members identified with a primary diagnosis on a medical claim for cardiovascular disease (CVD) from January 1, 2001 through December 31, 2002. Patients were categorized as: low risk (LR), high risk (HR), or high risk aged≥55 (HR55), based on the ONTARGET clinical trial. RESULTS: Most patients (85%) were in the LR category (8% in HR55, 7% in HR). A significantly greater proportion of patients in the HR55 group were hospitalized and experienced a greater number of ambulatory visits compared with LR and HR patients. Controlling for covariates, HR55 patients averaged $22,502 in paid healthcare services over 2 years versus $15,645 for HR patients and $11,423 for LR patients (p<0.001). CV-related costs represented about 46% of costs for the HR55 group, versus 41% for the HR group and 31% for the LR group. LIMITATIONS: Claims data are collected for the purpose of payment and not research and the presence of a diagnosis code is not proof of disease, due to possible coding errors or the use of a rule-out criterion. Also, patients who died in the follow-up were not included in the analyses, resulting in lower BOI estimates. Finally, the results of this study reflect treatment of CVD in managed-care settings, and may not be applicable to a different type of population. CONCLUSION: This study demonstrates the high BOI associated with CVD, especially for patients within the high-risk group aged≥55 years. Opportunities exist for reducing costs in this population.

Evaluating the impact of study-level factors on warfarin control in U.S.-based primary studies: a meta-analysis.

PURPOSE: The effect of study-level factors on the proportion of time spent with International Normalized Ratio (INR) values inside the therapeutic range in patients treated with warfarin in the United States was evaluated. METHODS: Studies evaluated in a previous meta-analysis were screened for potential inclusion, in addition to a systematic literature search of databases from January 2005 through February 2008. Studies were included if they (1) contained at least one warfarin dosing group that enrolled >25 patients for whom INR control was monitored for at least three weeks, (2) included only patients treated in the United States, (3) used a patient-time approach to report outcomes, and (4) reported proportion of time spent in the therapeutic INR range. Analyses included determining how study-level factors, such as study setting, year of study publication, INR interpolation method, study design, and presence of self-management, affected outcomes. RESULTS: Twenty-four studies, including a total of 43 unique warfarin groups, were included in the analysis. Overall, patients spent 57% of their time in the therapeutic range (95% confidence interval [CI], 55-59%). Compared with anticoagulation clinics, community management resulted in less time (-13%; 95% CI, -18% to -7.9%) and prospective studies resulted in more time (7.3%; 95% CI, 1.5-13.1%) spent in the therapeutic range than retrospective studies. When studies from both the United States and Canada were included, similar results to those in the base-case analysis were seen; however, study year and interpolation method were also found to be significant modifiers of INR control. CONCLUSION: Patients included in the meta-analysis maintained INR values within the therapeutic range 57% of the time, although the use of anticoagulation clinic services appeared to be superior to standard community care in this regard. However, patients treated in anticoagulation clinics had INR values within the therapeutic range less than two thirds of the time.

Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States.

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.