Study design and data source

This study aimed to compare HCRU and costs for patients newly diagnosed with NVAF and newly initiated on dabigatran or warfarin in a Medicare population. A retrospective matched-cohort study was conducted using the Humana Inc. administrative claims database. This database contains integrated medical claims, pharmacy claims, and enrollment data (Medicare or commercial plan type, member demographics, and coverage start and end dates), representing over 20 million current and former Humana members enrolled in commercial, Medicare Advantage, and prescription drug plans. The data have national coverage, with a high proportion of members from Texas, Florida, and Ohio. For this study, only the Medicare Advantage population was examined, since those who met the study criteria were predominantly Medicare members thus utilizing a majority population aged ≥65; socioeconomic status is not available in this data. Please see section on Study Population for details regarding other demographic variables that characterize this study population. The patient index date was determined using pharmacy claims and defined as the date of initiation of dabigatran or warfarin during the patient identification period from January 2011 to December 2011. Data were extracted for each patient for 12 months before the index date and up to 12 months after the index date; therefore, the full study period was from January 2010 to December 2012 (study inclusion/exclusion criteria explained in next section). The finalized protocol was approved by an independent institutional review board.

Study population

The study population consisted of patients newly diagnosed with NVAF and newly treated with dabigatran or warfarin (Fig. 1). Newly diagnosed was defined as the first AF diagnosis occurring within 3 months prior to index date and no other AF diagnosis in the >3 to 12 months before index date, while newly treated was defined as having no prescription fills for any OAC in the 12 months prior to index date. Patients were assigned to either dabigatran or warfarin cohort based on the index OAC. Inclusion criteria required patients to have the following: (1) ≥1 inpatient stay, ≥2 physician office visits, ≥2 emergency room (ER) visits, or a combination of 1 physician office visit and ER visit with an ICD-9 code of 427.31 (atrial fibrillation) on distinct service dates during the 3 month pre-index period (this definition is consistent with several previous studies conducted among NVAF patients); [26,27,28] (2) at least two fills of index exposure during the follow-up period (including fill on the index date); (3) 12 months of continuous enrollment prior to the index date. Criteria that excluded patients from the cohort included (1) any medical claim (inpatient stay, outpatient visit, or ER visit) with a diagnosis of hyperthyroidism or valvular heart disease during the 12 months pre-index; (2) any medical claim with a diagnosis of cardiac surgery, myocarditis, pericarditis, or pulmonary embolism (see Additional file 1 for codes) within 3 months prior to the first AF diagnosis; (3) <18 years of age or >89 years of age. A total of 1127 patients newly diagnosed with NVAF and newly initiated on dabigatran, and 3234 patients newly diagnosed with NVAF and newly initiated on warfarin were identified.

Fig. 1 Schematic of Patient Selection Full size image

Patient characteristics

Age, gender, race, and geographic region were reported as of the index date. The following variables derived from medical claims, were reported during the pre-index period: time from NVAF diagnosis to index date, duration of follow-up period, and comorbidities such as intracranial hemorrhage, gastrointestinal bleeding, other bleeding, ischemic stroke, heart failure, hypertension, and diabetes (see codes in Additional file 1) were assessed using medical claims for any inpatient stay, any two physician office visits or ER visits, or a combination of both (OV + ER). Clinical indexes including Deyo-Charlson [29] and Elixhauser comorbidity scores, [30] CHADS 2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack), [31] CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65–74 years, sex) [32] and HEMORR 2 HAGES [26] [hepatic or renal disease, ethanol abuse, malignancy, older age (>75), reduced platelet count or function, rebleeding risk, hypertension, anemia, genetic factors, excessive fall risk, stroke] risk scores were calculated during the pre-index period.

Propensity score matching

Propensity score matching (PSM) based on 1:1 nearest neighbor method with a caliper width of 0.2 standard deviations (SDs) of the estimated logit was used to match dabigatran and warfarin cohorts. Propensity score matching was conducted using logistic regression with predictor variables that were known to or could greatly impact the propensity to prescribe one medication over another based on information from the research literature [26] and expert clinical and research opinion (age, gender, geographic region, Deyo-Charlson comorbidity score, HEMORR2HAGES score, intracranial hemorrhage, gastrointestinal bleed, other bleed, ischemic stroke, heart failure, hypertension, and diabetes). In addition, bivariate analyses were conducted to identify differences at baseline among the study cohorts.

Outcomes

Patients were followed for up to 12 months post-index to evaluate HCRU and costs. End of follow-up was defined as disenrollment from the health plan, death, discontinuation (failure to refill within 30 days from the date of the previous prescription) or switch from the index medication, or end of study period (December 2012), whichever occurred first. All-cause HCRU based on primary diagnosis (see Additional file 1 for codes) was examined by place of service (inpatient hospital, ER visit, physician office visit, and other outpatient visits). Costs were estimated based on total payment to the provider, including both the plan cost and patient share. All-cause costs were presented as total costs (sum of medical and pharmacy costs), medical costs, and pharmacy costs; all costs were adjusted to 2012 dollars to account for inflation.

Statistical analyses

Demographic and baseline characteristics were compared among dabigatran and warfarin cohorts both pre- and post-PSM. Chi-square tests and t-tests or Wilcoxon rank-sum tests were conducted for categorical and continuous variables, respectively.

The number and rates of HCRU were reported as per-patient-per-year (PPPY, eg, PPPY rate was the number of hospitalizations/visits divided by the total patient years). All-cause HCRU was calculated as the count of distinct hospitalizations, ER visits, physician office visits, or outpatient visits. Since patients could have more than one hospitalization or visit, this number was greater than the count of patients. Patient years was calculated as the number of days a patient contributed to the denominator (ie, days from index prescription until discontinuation of therapy, switching of therapy, disenrollment, death, or end of study period) divided by 365. Descriptive statistics [N, mean, SD, median, and interquartile range (IQR)] were used to report all-cause HCRU and rates were compared using a Wilcoxon rank-sum test. Additionally, Cox regression analyses were used to investigate the association between anticoagulation treatment (dabigatran or warfarin) and time to first all-cause inpatient hospitalization and ER visit, adjusting for covariates. Hazard ratios (HRs) with 95% confidence intervals (CI) and P values were reported.