Long-term outcome in patients with non-valvular atrial fibrillation on dabigatran: a prospective cohort study.

INTRODUCTION: Most studies on thromboembolic and bleeding risk in patients with non-valvular atrial fibrillation (NVAF) exposed to non-vitamin K oral anticoagulants stem from interrogation of insurance databases. Areas covered: We studied 742 consecutive patients with NVAF who started treatment with dabigatran in three hospitals in Italy. Average follow-up was 1.80 years. Mean age was 76.2 years. CHA2DS2VASc score was 0-1 in 37 (5%), 2 in 97 (13%) and ≥ 3 in 604 (82%) patients. NVAF was permanent in 349 (48%). Overall, 76% of patients remained on treatment over the entire follow-up period. Among 180 patients who discontinued permanently, the most frequent reasons were dyspepsia (33.9%), bleeding (17.8%), and renal worsening (12.1%). About 48% and 74% of permanent discontinuations occurred during the first 6 and 12 months of treatment, respectively. Rates of major events (per 100 patient-years) were 0.75 for stroke, 0.31 for myocardial infarction, 1.50 for all-cause death, and 1.80 for major bleedings. The rate of intracranial bleedings was 0.45 and that of major gastrointestinal bleedings was 0.75. Expert opinion: This prospective cohort study confirms the low incidence of stroke, major bleeding and intracranial bleeding, and a 76% persistence with treatment, in patients with NVAF treated with dabigatran over about 2 years.

Permanent discontinuation of non vitamin K oral anticoagulants in real life patients with non-valvular atrial fibrillation.

BACKGROUND: Persistence to treatment affects clinical outcomes in patients with chronic disease such as atrial fibrillation (AF). METHODS: This prospective cohort study included consecutive non-valvular AF patients prescribed with non-vitamin K oral anticoagulants (NOACs) and investigated for any permanent discontinuation at 1-year of this therapy, as well as any reasons for discontinuation. RESULTS: Overall, 1305 patients were prescribed with dabigatran (N=473), rivaroxaban (N=425) or apixaban (N=407). Of these, 201 patients (15.4%) discontinued NOACs during the first year of treatment. More than 60% of these discontinuations occurred during the first 6months. Reasons for discontinuation included: dyspepsia or abdominal pain in 38 patients (2.9%) and bleeding in 59 (4.5%). Discontinuation for the former occurred earlier (50% within 2months) compared to the latter (66% after the first 4months). The prescription of reduced NOAC doses resulted being an independent predictor of discontinuation (OR 1.74, 95% CI 1.23-2.45, p=0.002). Regarding the use of dabigatran, rivaroxaban and apixaban, the following were observed: discontinuers were 22.0% (95% CI 18.5-25.9), 14.4% (95% CI 11.3-18.0) and 8.8% (95% CI 6.5-12.0), the risk of discontinuation associated with bleeding was 20.2%, 44.3% and 30.6% and dyspepsia or abdominal pain was 35.6%, 1.6% and 0%, respectively. CONCLUSION: Discontinuation of NOACs in AF patients was relatively common and more than often occurred in the first six months after prescription. Patients treated with reduced doses of NOACs had a higher probability to discontinue compared to those who were prescribed conventional doses.

Safety of dabigatran in an elderly population: single center experience in Italy.

In clinical practice, adherence to drugs and their safety may differ from randomised controlled trial settings. This study was undertaken to investigate the adherence to dabigatran, a direct thrombin inhibitor, and its safety in a real-world setting. We studied a prospective cohort of 114 elderly consecutive patients with non valvular atrial fibrillation (AF) who were treated with dabigatran 150 mg twice-daily (N=39) or 110 mg twice-daily (N=76). These patients were studied at baseline and after an average of 6 months. Mean age was 80 years and 53% were women. At entry, the average CHA2DS2VASc score was 4 and the HAS-BLED score was 2. AF was permanent in 49% of patients, persistent in 30%, paroxysmal in 12% and new-onset in 24%. In the follow-up clinical visit we ascertained vital status, adherence to treatment according to refill prescription orders, and side effects. Adherence was ≥80% in 76.5% of patients. Heartburn, the most frequent adverse effect, was reported by 25 patients (22%). Major and minor bleedings were experienced by 2 (1.8%) and 9 (7.9%) patients, respectively. Permanent discontinuation occurred in 18 patients (16%). The most frequent cause of permanent discontinuation was heartburn (10 patients). This real-life study suggests that safety of dabigatran and adherence to this drug in an elderly cohort of AF patients at high or very high risk of thromboembolism are generally good. Heartburn is the main cause of treatment discontinuation.