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.

Available epidemiological data on primary biliary cholangitis (PBC) in Sweden originate from regional studies in the 1980s and may not reflect modern day PBC. We aimed to estimate incidence and prevalence, survival and death causes, and gender differences in PBC. We used international classification of disease (ICD) codes to identify patients with PBC in inpatient and outpatient registries 1987–2014 who were then linked to the Swedish cause of death, cancer and prescribed drug registries. Each PBC patient was matched with 10 reference individuals from the general population. In sensitivity analyses, we examined PBC patients identified through clinical patient records from Karolinska, Sahlgrenska and Örebro University Hospitals. We identified 5,350 adults with PBC. Prevalence of PBC increased steadily from 5.0 (1987) to 34.6 (2014) per 100,000 inhabitants whereas the yearly incidence rate was relatively constant with a median of 2.6 per 100,000 person-years, with a female:male gender ratio of 4:1. Compared to reference individuals, PBC individuals aged 15–39 years at diagnosis had a substantially higher risk of death (Hazard Ratio [HR] 12.7, 95% Confidence Interval [CI] 8.3–19.5) than those diagnosed between 40–59 (HR 4.1, 95% CI 3.7–4.5) and >60 (HR 3.7, 95% CI 3.5–3.9) years of age. Relative risks of mortality were highest in men. In conclusion , we found that recorded prevalence of PBC in Sweden has increased substantially during the last 30 years although incidence has been stable. Patients diagnosed in young adulthood were at a 12.7-fold increased risk of death, and male PBC patients had worse prognosis.

ObjectivesTo 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.MethodsWe 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.ResultsAmong 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.ConclusionIn 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.

Purpose To develop and validate a risk score (P-score) algorithm which includes previously described three-gene signature and clinicopathological parameters to predict the risk of death from prostate cancer (PCa) in a retrospective cohort. Patients and Methods A total of 591 PCa patients diagnosed between 2003 and 2008 in Stockholm, Sweden, with a median clinical follow-up time of 7.6 years (1–11 years) were included in this study. Expression of a three-gene signature (IGFBP3, F3, VGLL3) was measured in formalin-fixed paraffin-embedded material from diagnostic core needle biopsies (CNB) of these patients. A point-based scoring system based on a Fine-Gray competing risk model was used to establish the P-score based on the three-gene signature combined with PSA value, Gleason score and tumor stage at diagnosis. The endpoint was PCa-specific mortality, while other causes of death were treated as a competing risk. Out of the 591 patients, 315 patients (estimation cohort) were selected to develop the P-score. The P-score was subsequently validated in an independent validation cohort of 276 patients. Results The P-score was established ranging from the integers 0 to 15. Each one-unit increase was associated with a hazard ratio of 1.39 (95% confidence interval: 1.27–1.51, p < 0.001). The P-score was validated and performed better in predicting PCa-specific mortality than both D’Amico (0.76 vs 0.70) and NCCN (0.76 vs 0.71) by using the concordance index for competing risk. Similar improvement patterns are shown by time-dependent area under the curve. As demonstrated by cumulative incidence function, both P-score and gene signature stratified PCa patients into significantly different risk groups. Conclusion We developed the P-score, a risk stratification system for newly diagnosed PCa patients by integrating a three-gene signature measured in CNB tissue. The P-score could provide valuable decision support to distinguish PCa patients with favorable and unfavorable outcomes and hence improve treatment decisions.