Dovepress not hospitalized on index. Two types of outcomes were analyzed for this study. First, clinical outcomes including hospitalization, stroke, TIA, and death were assessed in the variable follow-up period (up to 4 years). Second, index hospitalization, medical, pharmacy, and total costs of health care services were examined in the year following stroke. Costs were calculated as the patient and health plan paid amounts for services delivered (regardless of direct relationship to the condition of ‘stroke’) in the 12 months following discharge or index date among those with no hospitalization on index. Costs were adjusted to 2005 values based on the medical component of the Chained Consumer Price Index13 and were converted to a per-patient-per-year measure to account for the variable observation in the 12 months following the index date. independent variables Stroke and control cohorts were the primary variable of interest. In addition, age, gender, and US Census region in which the patient lived were derived from the enrollment data. Claims from the pre-index period were assessed for evidence of comorbid illnesses, specifically hypertension, diabetes, TIA, chronic obstructive pulmonary disease (COPD), con- gestive heart failure (CHF), and myocardial infarction (MI). statistical methods Bivariate comparisons between the stroke cohort and the control cohort were conducted for all study variables. For comparison of mean, t-tests were used for continuous measures and χ2 tests of differences in proportions were used for dichotomous or ordinal variables. All results are also shown for new and recurrent stroke patients, although no testing was performed. Costs, mortality, additional stroke, and additional hospitalization were further analyzed using appropriate multivariable statistical methods. Time to hospitalization, time to stroke, and time to death were analyzed using time-to-event analysis techniques to allow for differing follow-up times. Specifically, Cox proportional hazard models were estimated and Kaplan–Meier curves were presented for each of these outcomes. Wilcoxon and Log-rank tests were performed for the Kaplan–Meier analyses to test for differences across the cohorts. Tests of the proportional- ity assumption were performed for the Cox proportional hazards models to determine whether the hazards remained constant over time. Medical or pharmaceutical costs are difficult to model because of the skewed nature of the distribution of costs (ie, many subjects have minimal or no costs during the Vascular Health and Risk Management 2010:6 costs and outcomes of ischemic stroke study period whereas a few subjects have extremely high costs). Therefore, to compensate for the skewed distribution, we estimated costs using a generalized linear model with gamma distribution and log link. For the disease cohort variable, the coeff icients from the generalized linear modeling specification represent the ratio of expected costs in the disease cohort versus the control cohort. This method avoids potential difficulties introduced by transformation (eg, calculating the log of the costs) and retransformation of the dependent variable.14 Independent variables included the presence of stroke during the baseline period, age, gender, geographic region, and comorbid illness. Interaction terms between age and gender were tested and included in the models where statistically significant. SAS software (v. 8.2; SAS Institute Inc., Cary, NC) was used for creation of the analytic dataset and descriptive analyses, and STATA software (v. 9; StataCorp LP, College Station, TX) was used for multivariate analyses. Results Patient characteristics Of the 10.7 million health plan enrollees in the research database during the identification period from January 1, 2002, to December 31, 2003, 39,446 patients were identified with ischemic stroke, hemorrhagic stroke, unknown stroke, or TIA. From this group, patients were excluded due to mitral valve abnormality, AF, age, application of the 12-month pre- index continuous enrollment requirement, and finally down to patients with ischemic stroke on the index date. These patients were then matched 3:1 to controls. The final sample retained 2180 ischemic stroke patients, including 1808 new stroke patients and 372 recurrent stroke patients, and 6540 control patients. Table 1 shows the demographic and baseline charac- teristics of the study cohorts. Mean age of both the stroke and control cohorts was 59 (SD 13) years. More than half of all study patients were 55 years of age or older. Men represented 58.49% of the stroke and control cohorts. Within the stroke cohort, new stroke patients were more likely to be male (59.07%) compared with the recurrent stroke patients (55.65%). The recurrent stroke subgroup had a larger percentage of patients 65 years of age or older. The distribution across the four geographic regions was similar between the stroke and control cohorts, and across new and recurrent stroke patients; reflective of the distri- bution of the research database population, the majority of the patients were either from the Midwest (41.4%) or South (40.4%). submit your manuscript | www.dovepress.com Dovepress 907