Geographical variation in persistence to oral anticoagulation therapy and clinical outcomes among patients with atrial fibrillation initiating therapy in Denmark, Sweden, Norway and Finland.

AIM: To examine inter-national and regional variations in persistence of oral anticoagulation (OAC) therapy and incidence of clinical outcomes and mortality, among patients with incident atrial fibrillation (AF) in the Nordic countries. METHODS: We conducted a registry-based multinational cohort study of OAC-naïve patients diagnosed with AF that redeemed at least one prescription of OAC after AF in Denmark (N = 25 585), Sweden (N = 59 455), Norway (N = 40 046) and Finland (N = 22 415). Persistence was dispensing at least one prescription of OAC from Day 365 after the first prescription and 90 days forward. RESULTS: Persistence was 73.6% (95% confidence interval 73.0-74.1) in Denmark, 71.1% (70.7-71.4) in Sweden, 89.3% (88.2-90.1) in Norway and 68.6% (68.0-69.3) in Finland. One-year risk of ischemic stroke varied between 2.0% (1.8-2.1) in Norway and 1.5% (1.4-1.6) in Sweden and 1.5% (1.3-1.6) in Finland. One-year risk of major bleeding other than intracranial bleeding varied between 2.1% (1.9-2.2) in Norway and 5.9% (5.6-6.2) in Denmark. One-year mortality risk varied between 9.3% (8.9-9.6) in Denmark and 4.2% (4.0-4.4) in Norway. CONCLUSION: In OAC-naïve patients with incident AF, persistence of OAC therapy and clinical outcomes vary across Denmark, Sweden, Norway and Finland. Initiation of real-time efforts are warranted to ensure uniform high-quality care across nations and regions.

Effectiveness and safety of oral anticoagulants in elderly patients with atrial fibrillation.

OBJECTIVES: To assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF) in a real-world population. METHODS: We identified all anticoagulant-naive initiators of warfarin, dabigatran, rivaroxaban and apixaban for the indication AF in Norway between January 2013 and December 2017. Multivariate competing risk regression was used to calculate subhazard ratios (SHRs) describing associations between non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin for risk of stroke/SE and major bleeding. RESULTS: Among 30 401 patients ≥75 years identified (median age 82 years, 53% women, mean CHA2DS2-VaSc score 4.5), 3857 initiated dabigatran, 6108 rivaroxaban, 13 786 apixaban and 6650 warfarin. Reduced dose was initiated in 11 559 (49%) of the NOAC-treated patients. For stroke, the SHRs for standard dose NOAC against warfarin were 0.80 (95% CI 0.57 to 1.13) for dabigatran; 1.07 (95% CI 0.89 to 1.30) for rivaroxaban and 0.95 (95% CI 0.78 to 1.15) for apixaban. For major bleeding, the SHRs against warfarin were 0.75 (95% CI 0.52 to 1.08) for dabigatran; 0.96 (95% CI 0.78 to 1.16) for rivaroxaban and 0.74 (95% CI 0.60 to 0.91) for apixaban. Comparing reduced doses of NOACs with warfarin yielded similar results. Sensitivity analyses were in accordance with the main results. CONCLUSION: In this nationwide cohort study of patients ≥75 years initiating oral anticoagulation for AF, standard and reduced dose NOACs were associated with similar risks of stroke/SE as warfarin and lower or similar risks of bleeding. The NOACs seem to be a safe option also in elderly patients.

Comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in atrial fibrillation: a nationwide cohort study.

AIMS: The aim of this study was to compare the risk of stroke or systemic embolism (SE) and major bleeding in patients with atrial fibrillation (AF) using dabigatran, rivaroxaban, and apixaban in routine clinical practice. METHODS AND RESULTS: Using nationwide registries in Norway from January 2013 to December 2017, we established a cohort of 52 476 new users of non-vitamin K antagonist oral anticoagulants (NOACs) with AF. Users of individual NOACs were matched 1:1 on the propensity score to create three pairwise-matched cohorts: dabigatran vs. rivaroxaban (20 504 patients), dabigatran vs. apixaban (20 826 patients), and rivaroxaban vs. apixaban (27 398 patients). Hazard ratios (HRs) for the risk of stroke or SE and major bleeding were estimated. In the propensity-matched comparisons of the risk of stroke or SE, the HRs were 0.88 [95% confidence interval (CI) 0.76-1.02] for dabigatran vs. rivaroxaban, 0.88 (95% CI 0.75-1.02) for dabigatran vs. apixaban, and 1.00 (95% CI 0.89-1.14) for apixaban vs. rivaroxaban. For the risk of major bleeding, the HRs were 0.75 (95% CI 0.64-0.88) for dabigatran vs. rivaroxaban, 1.03 (95% CI 0.85-1.24) for dabigatran vs. apixaban, and 0.79 (95% CI 0.68-0.91) for apixaban vs. rivaroxaban. CONCLUSION: In this nationwide study of patients with AF in Norway, we found no statistically significant differences in risk of stroke or SE in propensity-matched comparisons between dabigatran, rivaroxaban, and apixaban. However, dabigatran and apixaban were both associated with significantly lower risk of major bleeding compared with rivaroxaban.

New score for assessing bleeding risk in patients with atrial fibrillation treated with NOACs.

Background: Information is needed on bleeding risk factors specific for patients with atrial fibrillation (AF) treated with non-vitamin K oral anticoagulants (NOACs). We aimed to identify risk factors in a large real-world cohort and to derive a bleeding risk score for patients with AF treated with NOACs. Methods: From nationwide registries (the Norwegian Patient Registry and the Norwegian Prescription Database), we identified patients with AF with a first prescription of a NOAC between January 2013 and June 2015. Cox proportional-hazards analysis was used to identify the strongest risk factors for major or clinically relevant non-major (CRNM) bleeding. Based on these, a risk prediction score was derived. Discrimination was assessed with Harrel's C-index. C-indexes for the modified Hypertension, Age, Stroke, Bleeding tendency/predisposition, Labile international normalised ratios, Elderly age, Drugs or alcohol excess (HAS-BLED), the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) and the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT) scores were also calculated from the same cohort. Results: Among 21 248 NOAC-treated patients with a median follow-up time of 183 days, 1257 (5.9%) patients experienced a major or CRNM bleeding. Ten independent risk factors for bleeding were identified, which when included in a risk prediction model achieved a C-index of 0.68 (95% CI 0.66 to 0.70). A simplified score comprising three variables; age, history of bleeding and non-bleeding related hospitalisation within the last 12 months, yielded a c-index of 0.66 (95% CI 0.65 to 0.68). In the same cohort, the modified HAS-BLED, ATRIA and ORBIT scores achieved c-indexes of 0.62 (95% CI 0.60 to 0.63), 0.66 (95% CI 0.64 to 0.67) and 0.66 (95% CI 0.64 to 0.67), respectively. Conclusions: Our proposed simplified bleeding score could be a useful clinical tool for quick estimation of risk of bleeding in patients with AF treated with NOACs.

New anticoagulants in combination with antiplatelet agents. / Nye antikoagulasjonsmidler i kombinasjon med platehemmere.

The use of new, direct anticoagulants is increasing. Data from both controlled trials and clinical practice have shown that these drugs are as efficacious and safe as warfarin for deep vein thrombosis and pulmonary embolism, and as stroke prophylaxis for patients with atrial fibrillation. But what if platelet inhibition is also indicated? In the following, the combination of antiplatelets and the new anticoagulants is discussed for various indications.