Géric Maura

Comparison of the short-term risk of bleeding and arterial thromboembolic events in nonvalvular atrial fibrillation patients newly treated with dabigatran or rivaroxaban versus vitamin K antagonists: a French nationwide propensity-matched cohort study.

Background— The safety and effectiveness of non–vitamin K antagonist (VKA) oral anticoagulants, dabigatran or rivaroxaban, were compared with VKA in anticoagulant-naive patients with nonvalvular atrial fibrillation during the early phase of anticoagulant therapy. Methods and Results— With the use of the French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort study included patients with nonvalvular atrial fibrillation who initiated dabigatran or rivaroxaban between July and November 2012 or VKA between July and November 2011. Patients presenting a contraindication to oral anticoagulants were excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by the use of 1:2 matching on the propensity score. Patients were followed for up to 90 days until outcome, death, loss to follow-up, or December 31 of the inclusion year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic events were estimated in an intent-to-treat analysis using Cox regression models. The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban new users. All dabigatran- and rivaroxaban-treated patients were matched to 16 014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-, and their VKA-matched–treated patients, 55 and 122 and 31 and 68 bleeding events and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during follow-up, respectively. After matching, no statistically significant difference in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64–1.21) or thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72–1.69) risk was observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95% confidence interval, 0.64–1.51) and ischemic (hazard ratio, 0.93; 95% confidence interval, 0.47–1.85) risks were comparable between rivaroxaban and VKA new users. Conclusions— In this propensity-matched cohort study, our findings suggest that physicians should exercise caution when initiating either non-VKA oral anticoagulants or VKA in patients with nonvalvular atrial fibrillation.

Risk of bleeding and arterial thromboembolism in patients with non-valvular atrial fibrillation either maintained on a vitamin K antagonist or switched to a non-vitamin K-antagonist oral anticoagulant: a retrospective, matched-cohort study

BACKGROUND Patients with non-valvular atrial fibrillation who are receiving or have been previously exposed to a vitamin K antagonist could be switched to a non-vitamin K-antagonist oral anticoagulant (NOAC) but little information is available about the risk of bleeding and arterial thromboembolism after such a switch. We aimed to compare the risk of bleeding between individuals who switched and those who remained on a vitamin K antagonist (non-switchers) in real-world conditions. METHODS We did a matched-cohort study with information from French health-care databases. We extracted data for adults (aged ≥18 years) with non-valvular atrial fibrillation who received their first prescription for a vitamin K antagonist (fluindione, warfarin, or acenocoumarol) between Jan 1, 2011, and Nov 30, 2012, and who were either switched to a NOAC (dabigatran or rivaroxaban) or maintained on the vitamin K antagonist. Each switcher was matched with up to two non-switchers on the basis of eight variables, including sex, age, and international normalised ratio number. The primary endpoint was incidence of bleeding (intracranial haemorrhage, gastrointestinal haemorrhage, or other) in switchers versus non-switchers, and switchers stratified by type of NOAC versus non-switchers, noted from databases of hospital admissions. Each patient was followed up to 1 year; the study closed on Oct 1, 2013. FINDINGS Of 17,410 participants, 6705 switched to a NOAC (switchers) and 10,705 remained on vitamin K-antagonist therapy (non-switchers). Median age of participants was 75 years (IQR 67-82), 8339 (48%) were women, and the median duration of vitamin K-antagonist exposure before a switch was 8.1 months (IQR 3.9-14.0). After a median follow-up of 10.0 months (IQR 9.8-10.0), we noted no difference between groups for bleeding events (99 [1%] in switchers vs 193 [2%] in non-switchers, p=0.54). In adjusted multivariate analyses, the risk of bleeding in switchers was not different from that in non-switchers (hazard ratio [HR] 0.87; 95% CI 0.67-1.13, p=0.30). Additionally, no differences were noted when the risk of bleeding was compared between switchers from a vitamin K antagonist to dabigatran (HR 0.78, 95% CI 0.54-1.09, p=0.15), switchers from a vitamin K antagonist to rivaroxaban (HR 1.04, 95% CI 0.68-1.58, p=0.86), and non-switchers. INTERPRETATION In this matched-cohort study, our findings suggest that patients with non-valvular atrial fibrillation who switch their oral anticoagulant treatment from a vitamin K antagonist to a non-vitamin K antagonist are not at increased risk of bleeding. Future studies with longer follow-up might be needed. FUNDING None.

Identifying atrial fibrillation in outpatients initiating oral anticoagulants based on medico-administrative data: results from the French national healthcare databases

Identifying atrial fibrillation (AF) in outpatients treated with oral anticoagulants (OACs) from claims databases is challenging when the outpatient indication is not available, as OACs are also prescribed for deep vein thrombosis/pulmonary embolism (DVT/PE) that may be treated in the ambulatory setting. An algorithm was developed to identify AF in outpatients initiating OAC from medico‐administrative data.

Prevalence and mortality of patients with multiple sclerosis in France in 2012: a study based on French health insurance data

Data on the prevalence of multiple sclerosis (MS) in France are scarce. National and regional updated estimates are needed to better plan health policies. In this nationwide study, we provided estimates of the prevalence of MS in France in 2012 and mortality rate in 2013. MS cases were identified in the French national health insurance database (SNIIRAM-PMSI) using reimbursement data for disease-modifying treatment, long-term disease status for MS, disability pension for MS, and hospitalisation for MS (MS ICD-10 code: G35). We identified 99,123 MS cases, corresponding to an overall crude prevalence rate of 151.2 per 100,000 inhabitants [95% confidence interval (CI) 150.3–152.2]: 210.0 per 100,000 in women (95% CI 208.4–211.5) and 88.7 per 100,000 in men (95% CI 87.6–89.7). The overall prevalence rate was 155.6 per 100,000 inhabitants (95% CI 154.7–156.6) after standardization on the 2013-European population. We observed a prevalence gradient with a higher prevalence (190–200 per 100,000) in North-Eastern France and a lower prevalence in Southern and Western France (126–140). The crude mortality rate in 2013 was 13.7 per 1,000 MS cases (11.4 in women and 20.3 in men). The standardized mortality ratio was 2.56 (95% CI 2.41–2.72). Our results revise upwards the estimation of MS prevalence in France and confirm the excess mortality of MS patients compared to the general population.

Trends in attention-deficit hyperactivity disorder medication use: a retrospective observational study using population-based databases

BACKGROUND The use of medications to treat attention deficit hyperactivity disorder (ADHD) has increased, but the prevalence of ADHD medication use across different world regions is not known. Our objective was to determine regional and national prevalences of ADHD medication use in children and adults, with a specific focus on time trends in ADHD medication prevalence. METHODS We did a retrospective, observational study using population-based databases from 13 countries and one Special Administrative Region (SAR): four in Asia and Australia, two in North America, five in northern Europe, and three in western Europe. We used a common protocol approach to define study populations and parameters similarly across countries and the SAR. Study populations consisted of all individuals aged 3 years or older between Jan 1, 2001, and Dec 31, 2015 (dependent on data availability). We estimated annual prevalence of ADHD medication use with 95% CI during the study period, by country and region and stratified by age and sex. We reported annual absolute and relative percentage changes to describe time trends. FINDINGS 154·5 million individuals were included in the study. ADHD medication use prevalence in 2010 (in children aged 3-18 years) varied between 0·27% and 6·69% in the countries and SAR assessed (0·95% in Asia and Australia, 4·48% in North America, 1·95% in northern Europe, and 0·70% in western Europe). The prevalence of ADHD medication use among children increased over time in all countries and regions, and the absolute increase per year ranged from 0·02% to 0·26%. Among adults aged 19 years or older, the prevalence of any ADHD medication use in 2010 varied between 0·003% and 1·48% (0·05% in Asia and Australia, 1·42% in North America, 0·47% in northern Europe, and 0·03% in western Europe). The absolute increase in ADHD medication use prevalence per year ranged from 0·0006% to 0·12%. Methylphenidate was the most commonly used ADHD medication in most countries. INTERPRETATION Using a common protocol and data from 13 countries and one SAR, these results show increases over time but large variations in ADHD medication use in multiple regions. The recommendations of evidence-based guidelines need to be followed consistently in clinical practice. Further research is warranted to describe the safety and effectiveness of ADHD medication in the short and long term, and to inform evidence-based guidelines, particularly in adults. FUNDING None.

Comparison of Treatment Persistence with Dabigatran or Rivaroxaban versus Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients: A Competing Risk Analysis in the French National Health Care Databases

Direct oral anticoagulants (DOACs) have been proposed as a more convenient alternative to vitamin K antagonists (VKAs), which are commonly associated with poor treatment persistence in non‐valvular atrial fibrillation (nv‐AF).

Clinical Events After Discontinuation of β‐Blockers in Patients Without Heart Failure Optimally Treated After Acute Myocardial Infarction: A Cohort Study on the French Healthcare Databases

Background: &bgr;-blockers have been among the first medications shown to improve outcomes after acute myocardial infarction (AMI). With the advent of reperfusion therapy and other secondary-prevention medications, their role has become uncertain, and large-scale experience after AMI in the contemporary era is lacking. In particular, the effect of stopping &bgr;-blockers in patients initially treated after AMI is unknown. Methods and Results: Using the French healthcare databases, 73 450 patients (<80 years of age), admitted for AMI in 2007 to 2012, without acute coronary syndrome (ACS) in the previous 2 years and no evidence of heart failure, having received optimal treatment with myocardial revascularization and all recommended medications in the 4 months after index admission, and not having discontinued &bgr;-blockers before 1 year, were followed for 3.8 years on average. &bgr;-Blocker discontinuation was defined as 4 consecutive months without exposure. If &bgr;-blocker treatment was resumed later on, follow-up was stopped. Both the risk of the composite outcome of death or admission for ACS and the risk of all-cause mortality were assessed in relation with &bgr;-blocker discontinuation during follow-up. Adjusted hazard ratios were estimated using marginal structural models accounting for time-varying confounders affected by previous exposure. A similar analysis was performed with statins. Of 204 592 patient-years, 12 002 (5.9%) corresponded to discontinued &bgr;-blocker treatment. For &bgr;-blocker discontinuation, the adjusted hazard ratio for death or ACS was 1.17 (95% confidence interval, 1.01–1.35); for all-cause death, the adjusted hazard ratio was 1.13 (95% confidence interval, 0.94–1.36). In contrast, for statin discontinuation, the adjusted hazard ratios for death or ACS and for all-cause death were 2.31 (95% confidence interval, 2.01–2.65) and 2.57 (95% confidence interval, 2.19–3.02), respectively. Conclusions: In routine care of patients without heart failure, revascularized and optimally treated after AMI, discontinuation of &bgr;-blockers beyond 1 year after AMI was associated with an increased risk of death or readmission for ACS, while statistical significance was not reached for the association with all-cause mortality. A contemporary randomized clinical trial is needed to precise the role of &bgr;-blockers in the long-term treatment after AMI.