Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: The NAXOS Study.

BACKGROUND AND PURPOSE: The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. METHODS: This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated. RESULTS: Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran. CONCLUSIONS: Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.

Asthma exacerbations and socio-economic status in French adults with persistent asthma: A prospective cohort study.

INTRODUCTION: Adults disadvantaged by poor socio-economic status (SES) are more severely affected by asthma compared to those with better SES. We aimed to determine whether the frequency of asthma exacerbations (AEx), as well as aspects related to AEx management, differed based on SES in patients treated with daily treatments. METHODS: This study, part of the prospective observational cohort ASTRO-LAB, included French adult patients with persistent asthma. Patients were considered as low SES if they benefited from publicly funded special health insurance and/or were perceived as low SES by their general practitioner. AEx was defined as at least one of the following: asthma-related oral corticosteroid course, medical contact, hospitalization, and death. We examined associations between SES and AEx frequency, perceived triggering factors and type of medical contact after AEx. RESULTS: In our sample of 255 patients, 11.40% were considered as low SES. Patients with low SES did not report significantly more AEx than medium/high SES patients during one-year follow-up (0.79 versus 0.55, p = 0.38). The type of medical contact during AEx differed significantly between the two groups (p = 0.03): patients with medium/high SES consulted their general practitioner more frequently (OR = 2.23, 95% CI = 0.91-5.50, p = 0.08) and were less likely to visit an emergency department or be hospitalized (OR = 0.27, 95% CI = 0.09-0.84, p = 0.02). CONCLUSIONS: AEx frequency did not differ significantly between low and medium/high SES patients, but differences were found in the management of AEx. Studies are needed to better understand the relation between precariousness and management of asthma.

Trajectories of Controller Therapy Use Before and After Asthma-Related Hospitalization in Children and Adults: Population-Based Retrospective Cohort Study.

BACKGROUND: Inappropriate use of inhaled corticosteroids (ICSs) for asthma impairs control and may cause exacerbation, including asthma-related hospitalization (ARH). In prospective studies, ICS use peaked around ARH, but information on routine care use is limited. Since ARH is a major outcome, controller therapy use in routine care before and after ARH should be documented. OBJECTIVE: This study aimed to distinguish ICS use typologies (trajectories) before and after ARH, and assess their relationships with sociodemographic, disease, and health care characteristics. METHODS: A retrospective cohort study was performed using a 1% random sample of the French claims database. All patients hospitalized for asthma between January 01, 2013, and December 31, 2015, were classified as either children (aged 1-10 years) or teens/adults (aged ≥11 years). Health care resource use was assessed between 24 and 12 months before ARH. ICS use was computed with the Continuous Measures of Medication Acquisition-7 (CMA7) for the 4 quarters before and after ARH. Initially, the overall impact of hospitalization on the CMA7 value was studied using a segmented regression analysis in both children and teens/adults. Then, group-based trajectory modeling differentiated the groups with similar ICS use. We tested different models having 2 to 5 distinct trajectory groups before selecting the most appropriate trajectory form. We finally selected the model with the lowest Bayesian Information Criterion, the highest proportion of patients in each group, and the maximum estimated probability of assignment to a specific group. RESULTS: Overall, 863 patients were included in the final study cohort, of which 447 (51.8%) were children and 416 (48.2%) were teens/adults. In children, the average CMA7 value was 12.6% at the start of the observation period, and there was no significant quarter-to-quarter change in the value (P=.14) before hospitalization. Immediately after hospitalization, the average CMA7 value rose by 34.9% (P=.001), before a significant decrease (P=.01) of 7.0% per quarter. In teens/adults, the average CMA7 value was 31.0% at the start, and there was no significant quarter-to-quarter change in the value (P=.08) before hospitalization. Immediately after hospitalization, the average CMA7 value rose by 26.9% (P=.002), before a significant decrease (P=.01) of 7.0% per quarter. We identified 3 and 5 trajectories before ARH in children and adults, respectively, and 5 after ARH for both groups. Trajectories were related to sociodemographic characteristics (particularly, markers of social deprivation) and to potentially inappropriate health care, such as medical management and choice of therapy. CONCLUSIONS: Although ARH had an overall positive impact on ICS use trajectories, the effect was often transient, and patient behaviors were heterogeneous. Along with overall trends, distinct trajectories were identified, which were related to specific patients and health care characteristics. Our data reinforce the evidence that inappropriate use of ICS paves the way for ARH.

Apixaban versus other anticoagulants in patients with nonvalvular fibrillation: a comparison of all-cause and event-related costs in real-life setting in France.

OBJECTIVES: Compare costs associated with all-cause healthcare resource use (HCRU), stroke/systemic thromboembolism (STE) and major bleedings (MB) between patients with non-valvular atrial fibrillation (NVAF) initiating apixaban or other oral anticoagulants (OACs). METHODS: We performed a retrospective cohort study using the French healthcare claims database, including NVAF patients between 2014/01/01 and 2016/12/31, followed until 2016/12/31. We used 4 sub-cohorts of OAC-naive patients, respectively initiating apixaban, dabigatran, rivaroxaban or VKAs. We matched patients initiating apixaban with patients initiating each other OACs using 1:n propensity score matching. All-cause HCRU and event-related costs by OAC treatment were estimated and compared between matched patients using generalised-linear models with gamma-distribution and two-part models. RESULTS: There were 175,766 patients in the apixaban-VKA, 181,809 in the apixaban-rivaroxaban, and 42,490 in the apixaban-dabigatran matched cohorts. Patients initiating apixaban had significantly lower HCRU costs than patients initiating VKA (€1,105 vs. €1,578, p < 0.0001), dabigatran (€993 vs. €1,140, p < 0.0001) and rivaroxaban (€1,013 vs. €1,088 p < 0.0001). They have had significantly lower costs related to stroke/STE and MB than patients initiating VKA (respectively, €183 vs. €449 and €147 vs. €413; p < 0.0001), rivaroxaban (respectively, €145 vs. €197 and €129 vs. €193; p < 0.0001), and lower costs related to stroke/STE than patients initiating dabigatran (€135 vs. €192, p < 0.02). Costs related to MB were not significantly different in patients initiating apixaban and those initiating dabigatran (€119 vs. €149, p = 0.07). CONCLUSIONS: HCRU and most event-related costs were lower in patients initiating apixaban compared to other OACs. Apixaban may be cost-saving compared to VKAs, and significantly cheaper than other DOACs, although cost differences are limited.

Cocooning strategy: Pertussis vaccination coverage rate of parents with a new-born in 2016 and 2017 in France.

Background: The "cocooning" strategy was introduced in 2004 to protect infants too young to be vaccinated against pertussis, by immunizing their parents and close relatives. The study objective was to assess its implementation 12 years after its introduction by estimating the pertussis vaccination coverage rates (VCR) among parents of newborns. Materials and methods: Pertussis VCR were estimated among all women who gave birth and men who took paternity leave, in 2016 or 2017, from a 1/97th random sample of French claims data. Two distinct study periods were defined based on current recommendations for the cocooning strategy: the "common practice" and the "parental project" periods. Results: In 2016, the pertussis VCR of women having given birth and men having taken paternity leave was 47.2 and 47.1%, respectively (46.1 and 45.6% in 2017, respectively). About one quarter of vaccinations were performed during the "parental project" period, with the vaccine most frequently reimbursed during the month of childbirth for women (57.1% in 2016 and 49.4% in 2017) and before or during the month the paternity leave began for men (about 78% in both 2016 and 2017). General practitioners were the main prescribers in private practice, even during the "parental project" period. Conclusion: To optimize the protection for infants, the main objective of the cocooning strategy, pertussis immunization coverage of adults and seniors needs to be improved. Moreover, cocooning vaccination linked to a parental project needs to be performed earlier, during pregnancy (for those around the mother) or in immediate post-partum (e.g., during the maternity stay).

Cancer incidence and prevalence in cystic fibrosis patients with and without a lung transplant in France.

Background: Cystic fibrosis (CF) care and the life expectancy of affected patients have substantially improved in recent decades, leading to an increased number of patients being diagnosed with comorbidities, including cancers. Our objective was to characterize the epidemiology of cancers between 2006 and 2017 in CF patients with and without a lung transplant. Methods: Medical records of CF patients from 2006 to 2016 in the French CF Registry were linked to their corresponding claims data (SNDS). The annual prevalence and incidence rates of cancers were estimated from 2006 to 2017 in CF patients without lung transplant and in those with lung transplant after transplantation. Results: Of the 7,671 patients included in the French CF Registry, 6,187 patients (80.7%) were linked to the SNDS; among them, 1,006 (16.3%) received a lung transplant. The prevalence of any cancer increased between 2006 and 2017, from 0.3 to 1.0% and from 1.3 to 6.3% in non-transplanted and transplanted patients, respectively. When compared to the general population, the incidence of cancer was significantly higher in both non-transplanted [Standardized Incidence Ratio (SIR) = 2.57, 95%CI 2.05 to 3.17] and transplanted (SIR = 19.76, 95%CI 16.45 to 23.55) patients. The median time between transplant and the first cancer was 3.9 years. Among the 211 incident cancer cases, the most frequent malignant neoplasms were skin neoplasm (48 cases), lung cancers (31 cases), gastro-intestinal (24 cases), and hematologic cancers (17 cases). Conclusion: The overall burden of cancer in CF patients is high, particularly following lung transplantation. Therefore, specific follow-up, screening and cancer prevention for CF patients with transplants are necessary.

Comparative non-persistence in the first year of treatment with oral anticoagulants in patients with atrial fibrillation: A French comprehensive nationwide study.

BACKGROUND: Direct oral anticoagulants (DOACs) were developed as an alternative to vitamin K antagonists (VKAs) and are commonly used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Unlike VKAs, DOACs do not require Internal Normalized Ratio (INR) monitoring, but regular intake is as important for effective anticoagulation. OBJECTIVES: This study examined treatment persistence among patients receiving oral anticoagulants (OACs) for NVAF. METHODS: Within the French healthcare claims database (SNDS), we assessed and compared the rates of non-persistence (≥ 30-day treatment gap) among patients with NVAF initiating an OAC between January 2014 and December 2016. The time-to-event of non-persistence was computed and plotted using a cumulative incidence function accounting for the competing risk of mortality. After adjusting on confounding factors, the risk for non-persistence was compared between apixaban and each other OACs using a Cox proportional hazard model, or Fine and Gray models. RESULTS: In a cohort of 321,501 OAC-naive patients with NVAF, the cumulative incidence of non-persistence at 12 months considering competing risk was 44.3%, 31.0%, 41.3% and 46.8% for VKAs, apixaban, rivaroxaban and dabigatran, respectively. Median therapy duration before non-persistence ranged between 70 and 121 days. Non-persistence was lower with apixaban compared with VKAs (HR=0.63, 95%CI=[0.62-0.64]), rivaroxaban (HR=0.71, 95%CI=[0.70-0.73]), and dabigatran (HR=0.60, 95%CI=[0.59-0.62]). CONCLUSIONS: In this nationwide observational study, non-persistence rates of oral anticoagulant treatment were high in patients treated for NVAF. Apixaban-treated patients seem to experience lowest discontinuation rates 12 months after treatment initiation compared to patients treated with any other OAC.

Antipsychotic prescribing practices in real-life (APPREAL study): Findings from the French National Healthcare System Database (2007-2017).

Background: Antipsychotics are used in a large variety of psychiatric and neurological disorders; investigating their use in real life is important to understand national prescribing practices, as well as to determine the levels of patient adherence. Methods: Using a 1/97e random sample (General Sample of Beneficiaries, EGB) of the French health insurance reimbursement database, we conducted a historical cohort study on the 2007-2017 period. The aim was to describe the sociodemographic characteristics of patients, the types of antipsychotics dispensed, the types of prescribers, the mean doses and average durations of treatment, the co-dispensed medications, and the levels of adherence to treatment. To exclude punctual uses of antipsychotics, we selected only patients with a continuous dispensing of the same antipsychotic over at least 3 months. Results: In total, 13,799 subjects (1.66% of the EGB sample) were included (56.0% females; mean age 55.8 ± 19.4 years). Risperidone (19.3%), cyamemazine (18.7%), olanzapine (11.9%), tiapride (8.8%), and haloperidol (7.5%) were the five most prescribed antipsychotics. 44.9% of prescriptions were written by general practitioners, 34.1% by hospital practitioners, and 18.4% by private-practice psychiatrists. On average, the mean dispensed doses were relatively low, but the variation range was large. Long-acting forms were used in 5.4% of the sample, and clozapine in 1.3%. 34.2% of patients received more than one antipsychotic, and almost 15% were prescribed at least three concomitant antipsychotics. Paliperidone and clozapine were associated with the highest levels of adherence, and risperidone and haloperidol with the lowest ones. Conclusion: An important heterogeneity of antipsychotic prescribing practices was observed in France. The rate of use of long-acting antipsychotics was low, whereas multiple antipsychotic prescriptions were frequent.

Vaccination coverage rates for Diphtheria, Tetanus, Poliomyelitis and Pertussis booster vaccination in France between 2013 and 2017: Learnings from an analysis of National Health System Real-World Data.

BACKGROUND: Maintaining a high vaccination coverage rate (VCR) throughout the lifetime and complying with the National Immunization Program are essential to optimize the protection of the population. The study objectives were to evaluate the evolution of the VCRs and the compliance with the vaccination visits for the diphtheria, tetanus, poliomyelitis and pertussis boosters in France since the changes implemented in the 2013 National Immunization Program. METHODS: Cumulative booster VCRs were estimated at all vaccination visits, from 2013 to 2017, among persons eligible for a booster vaccination from a 1/97th random sample of French claims data. Broader age groups around the recommended ages by the vaccination schedule (6, 11-13, 25, 45, 65, 75, 85, 95y) were used: all persons aged 5 to 8, 10 to 15, 21 to 29, 41 to 49, 61 to 69, 71 to 79, 81 to 89 and 91 to 99. RESULTS: Over the study period, the diphtheria-tetanus-poliomyelitis booster VCRs increased, reaching in 2017: 73.3% at 8 years old, 75.6% at 15 years old, 46.6% at 29 years old, 38.4% at 49 years old, 36.3% at 69 years old, 30.8% at 79 years old, 22.1% at 89 years old and 11.0% at 99 years old. The pertussis VCRs were also increasing at all vaccination visits, in particular at the vaccination visits at 6 and 11-13 years old (from 16.4% to 63.8% and from 50.3% to 61.2%, respectively). Delayed vaccinations were observed at all vaccination visits. CONCLUSION: VCRs for Diphtheria, Tetanus, Poliomyelitis and Pertussis booster vaccination increased from 2013 to 2017 while remaining suboptimal across all ages and lower in the adult populations. The analysis also shows that the introduction in 2013 of a pertussis vaccination at 6 years of age was relatively well-established in 2017 while other changes in recommendations were slowly or partially implemented.

Human papillomavirus (HPV) vaccine coverage rates (VCRs) in France: A French claims data study.

BACKGROUND: The French Cancer Plan 2014-2019 had a target of 60% HPV vaccine coverage. The PAPILLON study investigated the annual age-specific vaccination initiation rates and cumulative partial and complete vaccination rates in France from 2017 to 2022. It also identified the factors associated with vaccination in different age groups and those associated with the type of completion of the vaccination scheme (partial vs full vaccination). METHODS: For this publication, all females recorded in the French National Claims database who initiated HPV vaccination between 1 July 2007 and 31 December 2018 and were aged between 11 and 19 years at initiation were included. Annual HPV vaccination initiation rates were estimated in 11- to 14-year-old (target population) and 15- to 19-year-old females (catch-up). Cumulative vaccine coverage rates (VCRs) were estimated among those who were 15, 16, 20 and 21 years old. Partial vaccination was defined by dispensing of at least one dose of HPV vaccine by the pharmacy, while full vaccination was defined by two or three doses dispensed by a pharmacy over an 18-month period, according to current French recommendations based on the age at vaccination initiation. RESULTS: Among the 465,629 females who initiated HPV vaccination in 2017 or 2018, the initiation rate increased from 7.7 to 11.1% in 11- to 14-year-old girls and from 4.5 to 6.5% in 15- to 19-year-old females. In 2017 and 2018, the cumulative VCRs for partial vaccination by age 15 were 28.2% and 32.8%, respectively, while by age 20, they were 41.6% and 38.8%. The cumulative VCRs for full vaccination were 15.6% and 18.6% by age 16, while they were 25.9 and 23.6% by age 20. HPV vaccination initiation and completion were strongly associated with the use of health services. CONCLUSION: Overall, the HPV VCR substantively increased between 2017 and 2018, which is positive evidence of the resumption of vaccination. Updates in 2022 should confirm these results.

Impact of Therapy Persistence on Exacerbations and Resource Use in Patients Who Initiated COPD Therapy.

Purpose: This study assessed therapy persistence in patients with chronic obstructive pulmonary disease (COPD) in France, and the impact of non-persistence on exacerbations and described COPD-related healthcare resource use (HRU). Methods: Patients aged ≥45 years who received ≥1 dispensed bronchodilator per quarter over three consecutive quarters between 2007 and 2014 and initiated specific COPD therapy were selected from the Echantillon Généraliste des Bénéficiaires (EGB) database. Persistence, defined as the absence of dispensing gaps of >90 days, was measured at 12 months. Exacerbations were compared between persistent and non-persistent patients during follow-up after patient matching and adjustment for confounding factors. COPD-related HRU during follow-up was described. Results: Among 4020 patients with COPD, 2164 initiated a specific therapy. Of these, 54.4% stopped treatment within 12 months. Persistence with all COPD therapy regimens was low, particularly for inhaled corticosteroid (ICS; 25.6%) and ICS/twice-daily long-acting beta-agonist (39.4%) regimens. Among 721 persistent patients who were matched with 721 non-persistent patients, there was no difference in the number of moderate or severe exacerbations at 12 months. However, medical procedures (for instance, pulmonary function testing and chest X-rays) were more frequently observed among persistent patients than among non-persistent patients, suggesting worse disease severity. Conclusion: Patients receiving specific treatment(s) for COPD demonstrated low persistence for all examined therapy regimens, with no clear impact of persistence status on the frequency of exacerbations at 12 months.