Adherence, Persistence, and Switching Patterns of Dabigatran Etexilate | Page 2
Published Online: September 16, 2013
Kimberly Tsai, PharmD; Sara C. Erickson, PharmD; Jianing Yang, MS; Ann S. M. Harada, PhD, MPH; Brian K. Solow, MD; and Heidi C. Lew, PharmD
All statistical tests were performed using SAS version 9.2. Means were tested for variance and compared by independent t tests, and proportions were compared using the χ2 test. All comparisons were 2-sided and performed at a 0.05 level of significance.
There were 7322 patients identified for the warfarin-naïve cohort, and 10,369 patients identified for the warfarin-experienced cohort (Table 1). The average age of the study population was 76 years, and the majority of patients were enrolled in a PDP plan (77.2% for the warfarin-naïve cohort and 80.6% for the warfarin-experienced cohort, P <.001). Chronic concomitant conditions included hypertension (88.9% and 92.6% of the warfarin-naïve and warfarin-experienced cohorts, respectively, P <.001), CHD (69.8% and 71.9% of the warfarin-naïve and warfarin-experienced cohorts, respectively, P = .002), and dyslipidemia (58.2% and 63.0% of the warfarin-naïve and warfarin-experienced cohorts, respectively, P <.001). Warfarin-naïve patients had a mean of 6.4 total prescriptions (including dabigatran), and warfarin-experienced patients had a mean of 7.5 total prescriptions (including dabigatran) with days supply on the index date (P <.001). The mean Chronic Disease Scores were 4.2 and 6.4 (P <.001) for tively. While other statistically significant differences were observed for characteristics between the cohorts, a number of the statistically significant differences may be driven by the large population size and may not be of clinical significance.
The number of patients persistent to dabigatran therapy was 4137 (56.5%) in the warfarin-naïve cohort and 6492 (62.6%) in the warfarin-experienced cohort (P <.001) (Table 2). Of all 17,691 patients, 7062 (39.9%) were nonpersistent to dabigatran therapy over the 6-month period. Adherence was determined using PDC for the overall population and also for patients persistent to dabigatran therapy. The mean PDC for patients persistent to dabigatran therapy was 0.935 (standard deviation [SD] 0.075) for the warfarin-naïve cohort and 0.937 (SD 0.074) for the warfarin-experienced cohort (P = .28). In the overall population, the mean PDC was 0.674 (SD 0.364) for the warfarin-naïve cohort and 0.712 (SD 0.354) for the warfarin-experienced cohort (P <.001).
Among patients discontinuing dabigatran therapy, the mean time to discontinuation in warfarin-naïve and warfarinexperienced cohorts, respectively, was 59.8 (SD 36.2) days the warfarin-naïve and warfarin-experienced cohorts, respectively, was 59.8 (SD 36.2) days and 59.6 (SD 36.2) days (P = .83), with approximately 50% of patients discontinuing after the first 30-day fill of dabigatran. The mean time to initiating warfarin in warfarin-naïve and warfarin-experienced cohorts, respectively, was 62.5 (SD 47.2) and 60.5 (SD 43.0) days (P = .35) (Table 3, Figure 1, Figure 2). The number of patients nonpersistent to dabigatran therapy who switched to warfarin was 513 (16.1%) in the warfarin-naïve cohort and 1595 (41.1%) in the warfarinexperienced cohort (P <.001). The Kaplan-Meier curves for the time to discontinuation and time to switch to warfarin are shown in Figures 1 and 2.
Patients with a history of warfarin use prior to initiating dabigatran therapy had a greater burden of comorbidity than those without prior warfarin use, as demonstrated by a greater prevalence of CHF, DM, HTN, CHD, dyslipidemia, a higher CDS score, and a greater total number of medications compared with warfarin-naïve patients. Other statistically significant differences between the cohorts were likely driven by the large size of the study population. Examples of variables with small, but statistically significant, differences include mean age (76.0 years in warfarin-naïve versus 76.7 years in warfarin-experienced patients, P <.001), patients with concomitant diabetes mellitus (21.2% in warfarin-naïve vs 22.5% in warfarin-experienced patients, P = .03), and the percentage of patients with PDP coverage (77.2% in warfarin-naïve vs 80.6% in warfarin-experienced patients, P <.001). Among patients persistent to dabigatran therapy, both cohorts demonstrated good adherence with mean PDC values of 0.935 (warfarin-naïve) and 0.937 (warfarin-experienced). The suboptimal adherence of the overall cohort (including both patients persistent and nonpersistent to dabigatran therapy) appears to be attributed to nonpersistence. In the overall study cohort, 40% of patients were nonpersistent to dabigatran therapy (ie, discontinued dabigatran therapy). In patients nonpersistent to dabigatran therapy, the mean trial of dabigatran (ie, time to discontinuation) was a length of 60 days.
Among patients who were nonpersistent to dabigatran therapy, approximately 50% of patients discontinued by 30 days and approximately 80% had discontinued by 90 days. The observed decline in persistence at these points likely reflects discontinuation after only the first fill (either a 30- or 90-day supply). Of patients switching to warfarin, the mean time to switch was also approximately 60 days. In patients nonpersistent to dabigatran therapy, the majority did not switch to warfarin in either cohort. This suggests that most patients may discontinue dabigatran without being switched to warfarin, despite the need for patients with atrial fibrillation to be persistent to chronic anticoagulation therapy. It is possible that patients may have discontinued dabigatran therapy at their own discretion without informing their healthcare providers. If this is the case, then patients taking dabigatran still may require closer monitoring, in spite of the lack of need for laboratory monitoring with dabigatran therapy. It may be necessary for healthcare professionals and managed care organizations to provide additional support and counseling for patients on dabigatran therapy.
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