Dabigatran was expected to replace warfarin for stroke prevention in patients with nonvalvular atrial fibrillation (AF) who are warfarin naive, difficult to maintain in therapeutic range, or at risk of warfarin-related bleeding complications. We hypothesized that the number of patients with nonvalvular AF referred to Anticoagulation Management Services would decrease sharply and that most would switch from warfarin to dabigatran. We evaluated the number of patients with nonvalvular AF referred to 2 large services, Anticoagulation Management Service 1 and Anticoagulation Management Service 2, 12 months before and after market entry of dabigatran. We also evaluated the number of patients who switched from warfarin to dabigatran. Anticoagulation Management Service 1 follows 1,225 patients with nonvalvular AF with mean CHADS 2 and CHA 2 DS 2 -VASc scores of 2.0 and 3.5, respectively. Anticoagulation Management Service 2 follows 1,137 patients with nonvalvular AF with mean CHADS 2 and CHA 2 DS 2 -VASc scores of 2.0 and 3.3, respectively. In the 12 months preceding market entry of dabigatran, patients with nonvalvular AF constituted 537 (31.4%) of the referrals sent to Anticoagulation Management Service 1 and increased to 793 (32.3%) in the following 12 months. For Anticoagulation Management Service 2, patients with nonvalvular AF constituted 617 (30.7%) of referrals before market entry of dabigatran and decreased to 495 (25.2%) of referrals. Eighty-one patients (6.6%) from Anticoagulation Management Service 1 and 44 (3.9%) from Anticoagulation Management Service 2 have switched from warfarin to dabigatran. The frequency of initial prescription of dabigatran for stroke prevention in AF and the frequency of transition from warfarin to dabigatran have been less than expected.
Dabigatran is prescribed in a fixed dose, requires no laboratory coagulation monitoring, and has minimal drug-food and drug-drug interactions. Dabigatran 150 mg twice daily was shown to decrease the rate of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) by 1/3, while also decreasing the risk of intracranial bleeding by 2/3 compared with warfarin. On the basis of ease of administration, superior efficacy, and superior safety with respect to intracranial hemorrhage, it was anticipated that dabigatran would replace warfarin for many patients. Consequently, we followed patients referred to 2 Anticoagulation Management Services for stroke prevention in nonvalvular AF with the aim of determining how the rate of referral for warfarin management would be affected and to determine how many existing patients would be switched from warfarin to dabigatran.
Methods
We identified all patients referred for anticoagulation management at 2 large anticoagulation management clinics, Anticoagulation Management Service 1 (Brigham and Women’s Hospital, Boston, Massachusetts) and Anticoagulation Management Service 2, (University of Michigan, Ann Arbor, Michigan) for 12 months before and after dabigatran market entry. Anticoagulation Management Service 1 and Anticoagulation Management Service 2 used electronic health records to capture baseline demographics, congestive heart failure, hypertension, age, diabetes mellitus, previous stroke or systemic thromboembolism (CHADS 2 ) and congestive heart failure, hypertension, age ≥65 years, age ≥75 years, diabetes, previous stroke or systemic thromboembolism, vascular disease, and female gender (CHA 2 DS 2 -VASc) prediction scores, and referral information. We determined total referred patients with nonvalvular AF in each clinic. We evaluated the number of patients with nonvalvular AF who switched from warfarin to dabigatran on a monthly basis. We calculated the percentage of nonvalvular AF referrals on a monthly basis to assess for changes in the distribution of diagnoses in each clinic population.
We compared patient characteristics in Anticoagulation Management Service 1 with Anticoagulation Management Service 2. Continuous variables were expressed as mean and SD, categorical data as real numbers and percentages. Differences in continuous data were analyzed using a Student’s t test. Differences in proportions were analyzed using a chi-square test. All reported p values are 2 tailed. All statistical analyses were performed using the Simple Interactive Statistical Analysis software available at http://www.quantitativeskills.com/sisa/ (Quantitative Skills, Consultancy for Research and Statistics, The Netherlands). Our study was approved by the Partners Healthcare System and University of Michigan Health System Human Research Committees.
Results
We collected data on 1,225 patients with nonvalvular AF in Anticoagulation Management Service 1 and 1,229 patients with nonvalvular AF in Anticoagulation Management Service 2. CHADS 2 and CHA 2 DS 2 -VASc scores were similar in the 2 clinic populations ( Table 1 ). Anticoagulation Management Service 1 had a greater number of patients with age ≥75 years (638 vs 429, p <0.001). Anticoagulation Management Service 2 had a greater number of patients with congestive heart failure (274 vs 533, p <0.001), hypertension (827 vs 946, p <0.001), and vascular disease (415 vs 472, p = 0.02).
| Characteristic | Anticoagulation Management Service-1 (n = 1,225) | Anticoagulation Management Service-2 (n = 1,229) | p |
|---|---|---|---|
| Mean age ± SD, yrs | 73.6 ± 11.4 | 67.6 ± 13.7 | 1.0 |
| CHADS 2 score, mean ± SD | 2.0 ± 1.3 | 2.0 ± 1.3 | 1.0 |
| CHADS 2 score, median (IQR) | 2 (2) | 2 (0) | — |
| CHA 2 DS 2 -VASc score, mean ± SD | 3.5 ± 1.7 | 3.3 ± 1.9 | 1.0 |
| CHA 2 DS 2 -VASc score, median (IQR) | 4 (3) | 3 (2) | — |
| Congestive heart failure (%) | 274 (22.4) | 533 (43.4) | <0.001 |
| Hypertension (%) | 827 (67.5) | 946 (78.0) | <0.001 |
| Age ≥75 yrs (%) | 638 (52.1) | 429 (34.9) | <0.001 |
| Diabetes (%) | 306 (25.0) | 326 (26.5) | 0.38 |
| Previous stroke or transient ischemic attack (%) | 183 (14.9) | 208 (16.9) | 0.18 |
| Vascular disease (%) | 415 (33.9) | 472 (38.4) | 0.02 |
| Age 65–75 yrs (%) | 328 (26.8) | 314 (25.5) | 0.49 |
| Women (%) | 476 (38.9) | 482 (39.2) | 0.85 |
From October 2009 through October 2011, Anticoagulation Management Service 1 received 4,165 referrals for patients with any indication for oral anticoagulation and Anticoagulation Management Service 2 received 3,974 ( Figure 1 ). In the 12 months preceding dabigatran market entry, patients with nonvalvular AF constituted 537 (31.4%) of the referrals sent to Anticoagulation Management Service 1 and increased to 793 (32.3%) in the following 12 months. For Anticoagulation Management Service 2, patients with nonvalvular AF constituted 617 (30.7%) of referrals before market entry of dabigatran and decreased to 495 (25.2%) of referrals. At the time of this analysis, 81 patients from Anticoagulation Management Service 1 and 44 from Anticoagulation Management Service 2 have switched from warfarin to dabigatran.
