Pierre-Olivier Blotière

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.

Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study.

Objective To assess the risk of pulmonary embolism, ischaemic stroke, and myocardial infarction associated with combined oral contraceptives according to dose of oestrogen (ethinylestradiol) and progestogen. Design Observational cohort study. Setting Data from the French national health insurance database linked with data from the French national hospital discharge database. Participants 4 945 088 women aged 15-49 years, living in France, with at least one reimbursement for oral contraceptives and no previous hospital admission for cancer, pulmonary embolism, ischaemic stroke, or myocardial infarction, between July 2010 and September 2012. Main outcome measures Relative and absolute risks of first pulmonary embolism, ischaemic stroke, and myocardial infarction. Results The cohort generated 5 443 916 women years of oral contraceptive use, and 3253 events were observed: 1800 pulmonary embolisms (33 per 100 000 women years), 1046 ischaemic strokes (19 per 100 000 women years), and 407 myocardial infarctions (7 per 100 000 women years). After adjustment for progestogen and risk factors, the relative risks for women using low dose oestrogen (20 µg v 30-40 µg) were 0.75 (95% confidence interval 0.67 to 0.85) for pulmonary embolism, 0.82 (0.70 to 0.96) for ischaemic stroke, and 0.56 (0.39 to 0.79) for myocardial infarction. After adjustment for oestrogen dose and risk factors, desogestrel and gestodene were associated with statistically significantly higher relative risks for pulmonary embolism (2.16, 1.93 to 2.41 and 1.63, 1.34 to 1.97, respectively) compared with levonorgestrel. Levonorgestrel combined with 20 µg oestrogen was associated with a statistically significantly lower risk than levonorgestrel with 30-40 µg oestrogen for each of the three serious adverse events. Conclusions For the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial thromboembolism compared with levonorgestrel. For the same type of progestogen, an oestrogen dose of 20 µg versus 30-40 µg was associated with lower risks of pulmonary embolism, ischaemic stroke, and myocardial infarction.

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.

Coût de la prise en charge de l’IRCT en France en 2007 et impact potentiel d’une augmentation du recours à la dialyse péritonéale et à la greffe

INTRODUCTION This study estimates the costs for the national health insurance in 2007 of the patients with end-stage renal disease (ESRD) according to therapies modalities. METHOD Data for all patients covered by the general health insurance scheme (77% of the French population) from hospital discharge and outpatients reimbursement databases were linked. ESRD therapies were identified using an algorithm mainly based on discharge diagnosis and immunosuppressive drugs refunds. RESULTS Extrapolated to all French population at the end of 2007, 60,900 patients had an ESRD therapy: 30,900 were treated on haemodialysis (HD) (51%), 2600 on peritonea dialysis (DP) (4%) and 27,300 had a kidney transplant (45%). Patients with dialysis therapies had more often complementary universal coverage for low earners. According to the French regions, patient treated with DP were between 0 to 26% and 19 to 57% for those with a transplant. The total refund cost for National Health Insurance was four billion euro of which 77% for HD. Annual mean costs per patient were 64 keuro for DP, 89 keuro for HD, 86 keuro for the year of transplantation and 20 keuro for the following years. A 25% increase of DP would allow a decrease of the annual cost of 155 millions euro and 900 transplantations more each year during 10 years a decrease of 2.5 billions euro. CONCLUSION The increase of ESRD prevalence and its total cost require patients and professionals information and formation about the less expensive and more autonomous therapies and others alternatives facing the lack of kidney transplants from deceased donors.

The Best Use of the Charlson Comorbidity Index With Electronic Health Care Database to Predict Mortality.

Background:The most used score to measure comorbidity is the Charlson index. Its application to a health care administrative database including International Classification of Diseases, 10th edition (ICD-10) codes, medical procedures, and medication required studying its properties on survival. Our objectives were to adapt the Charlson comorbidity index to the French National Health Insurance database to predict 1-year mortality of discharged patients and to compare discrimination and calibration of different versions of the Charlson index. Methods:Our cohort included all adults discharged from a hospital stay in France in 2010 registered in the French National Health Insurance general scheme. The pathologies of the Charlson index were identified through ICD-10 codes of discharge diagnoses and long-term disease, specific medical procedures, and reimbursement of specific medications in the past 12 months before inclusion. Results:We included 6,602,641 subjects at the date of their first discharge from medical, surgical, or obstetrical department in 2010. One-year survival was 94.88%, decreasing from 98.41% for Charlson index of 0–71.64% for Charlson index of ≥5. With a discrimination of 0.91 and an appropriate calibration curve, we retained the crude Cox model including the age-adjusted Charlson index as a 4-level score. Conclusions:Our study is the first to adapt the Charlson index to a large health care database including >6 million of inpatients. When mortality is the outcome, we recommended using the age-adjusted Charlson index as 4-level score to take into account comorbidities.

Perforations and haemorrhages after colonoscopy in 2010: A study based on comprehensive French health insurance data (SNIIRAM)

BACKGROUND AND OBJECTIVE To estimate the perforation and haemorrhage rate after colonoscopy in the French population in 2010 and to identify risk factors for these complications. METHOD Study based on SNIIRAM and the PMSI databases. Patients treated for IBD or colorectal cancer were excluded. Two types of complications were investigated: perforation and haemorrhage. OR adjusted for patient (gender, age, chronic disease) and colonoscopy (polypectomy, emergency) characteristics were calculated by using a logistic regression model. RESULTS The cohort was composed of 947,061 individuals. The estimated perforation rate was between 4.5 and 9.7 per 10,000 procedures and the estimated haemorrhage rate was between 9.9 and 11.0 per 10,000 procedures. The main risk factors associated with perforation and haemorrhage were the patients age (over 80 years compared to under 40, OR=7.51 and 3.23), resection of polyps larger than 1 cm or more than 4 polyps (compared to no polypectomy, OR=2.72 and 5.12) and emergency colonoscopy (OR=4.63 and 5.99). Colonoscopy performed by a gastroenterologist performing less than 244 colonoscopies per year was associated with an increased risk of perforation (OR=2.29). Complication rates were higher in institutions performing less than 510 colonoscopies per year, but this was no longer the case after adjustment for emergency colonoscopies. CONCLUSIONS This study, which includes nearly one million colonoscopies, suggests taking the gastroenterologists number of colonoscopies into account to ensure optimal organization of the management of very elderly patients requiring colonoscopy.

Dental procedures, antibiotic prophylaxis, and endocarditis among people with prosthetic heart valves: nationwide population based cohort and a case crossover study

Objective To assess the relation between invasive dental procedures and infective endocarditis associated with oral streptococci among people with prosthetic heart valves. Design Nationwide population based cohort and a case crossover study. Setting French national health insurance administrative data linked with the national hospital discharge database. Participants All adults aged more than 18 years, living in France, with medical procedure codes for positioning or replacement of prosthetic heart valves between July 2008 and July 2014. Main outcome measures Oral streptococcal infective endocarditis was identified using primary discharge diagnosis codes. In the cohort study, Poisson regression models were performed to estimate the rate of oral streptococcal infective endocarditis during the three month period after invasive dental procedures compared with non-exposure periods. In the case crossover study, conditional logistic regression models calculated the odds ratio and 95% confidence intervals comparing exposure to invasive dental procedures during the three month period preceding oral streptococcal infective endocarditis (case period) with three earlier control periods. Results The cohort included 138 876 adults with prosthetic heart valves (285 034 person years); 69 303 (49.9%) underwent at least one dental procedure. Among the 396 615 dental procedures performed, 103 463 (26.0%) were invasive and therefore presented an indication for antibiotic prophylaxis, which was performed in 52 280 (50.1%). With a median follow-up of 1.7 years, 267 people developed infective endocarditis associated with oral streptococci (incidence rate 93.7 per 100 000 person years, 95% confidence interval 82.4 to 104.9). Compared with non-exposure periods, no statistically significant increased rate of oral streptococcal infective endocarditis was observed during the three months after an invasive dental procedure (relative rate 1.25, 95% confidence interval 0.82 to 1.82; P=0.26) and after an invasive dental procedure without antibiotic prophylaxis (1.57, 0.90 to 2.53; P=0.08). In the case crossover analysis, exposure to invasive dental procedures was more frequent during case periods than during matched control periods (5.1% v 3.2%; odds ratio 1.66, 95% confidence interval 1.05 to 2.63; P=0.03). Conclusion Invasive dental procedures may contribute to the development of infective endocarditis in adults with prosthetic heart valves.

Surmortalité et hospitalisations plus fréquentes des bénéficiaires de la couverture médicale universelle complémentaire en 2009

AIM Complementary Universal Health insurance (CMUC) providing free access to health care has been available in France since 2000 for people with an annual income less than 60% of the poverty threshold. Hospital admission and mortality rates in 2009 were compared between beneficiaries of the general scheme under the age of 60 years with (4.5 millions) or without CMUC (34.1 millions) in 2008 and still alive at the end of the year. METHODS Data were derived from the French national health insurance reimbursements and short-stay hospital admissions database for 2009 (80% of subjects under the age of 60 years in France). Rates and relative risks (RR) were standardised for the gender and age. RESULTS CMUC beneficiaries had greater overall mortality rates (3.32/1000 vs. 1.36/1000, RR=2.4) for both gender (males RR=2.6, females RR=2.1) and each 10 years age class below 60 years. Standardised hospitalisation rate of CMUC beneficiaries was 17.5% and the rate for non-CMUC beneficiaries was 13.2%. Among CMUC beneficiaries, admissions were significantly more frequent for the following activity groups: toxicology, intoxication and alcohol (RR=3.5), psychiatry (RR=2.8), burns (2.7), respiratory medicine (RR=1.9), infectious disease (RR=2.1), endocrinology and cardiology (RR=1.7), obstetrics (RR=1.6). Their hospital mortality rate was also significantly higher (8.9/1000 vs. 5.1/1000, RR=1.73). CONCLUSION In this low income population with free access to health care, hospitalisation and hospital mortality rates were higher for many diseases that are more or less known targets for prevention and screening actions.

Conditions of prescription of anti-TNF agents in newly treated patients with inflammatory bowel disease in France (2011–2013)

BACKGROUND Tumour necrosis factor inhibitors (anti-TNFs) are active but expensive drugs that induce and maintain remission in patients with Crohns disease (CD) and ulcerative colitis (UC). AIMS To assess the trends in anti-TNF prescription and the conditions of prescription of these drugs in patients with inflammatory bowel disease (IBD) in France. METHODS Incidence study of anti-TNF use was performed based on French medico-administrative databases (SNIIRAM/PMSI). IBD patients who initiated adalimumab or infliximab between 2011 and 2013 were selected. RESULTS The number of new anti-TNF users increased from 4571 to 5875 between 2011 and 2013 (+29%). More specifically, the number of patients not treated with immunosuppressants (IS) during the previous 12 months increased from 2100 to 3007 (+43%), among whom 379 patients in 2011 and 570 patients in 2013 started combination therapy (+50%). These trends were observed for both CD and UC. Patients who were naïve of IS were hospitalised more frequently than those treated with IS prior to anti-TNF therapy. CONCLUSION This study shows a rapid increase in new prescriptions of anti-TNF for both CD and UC in France between 2011 and 2013. These results suggest a change in medical practices, with anti-TNF agents prescribed more often as first-line maintenance treatment.

Development of an algorithm to identify pregnancy episodes and related outcomes in health care claims databases: An application to antiepileptic drug use in 4.9 million pregnant women in France

Access to claims databases provides an opportunity to study medication use and safety during pregnancy. We developed an algorithm to identify pregnancy episodes in the French health care databases and applied it to study antiepileptic drug (AED) use during pregnancy between 2007 and 2014.