Cardiovascular and renal diseases in type 2 diabetes patients: 5-year cumulative incidence of the first occurred manifestation and hospitalization cost: a cohort within the French SNDS nationwide claims database.

BACKGROUND: Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal diseases (CVRD) manifestations for type 2 diabetes. The objective was to estimate the incidence of the first occurring CVRD manifestation and cumulative hospitalization costs of each CVRD manifestation for type 2 diabetes without CVRD history. METHODS: A cohort study of all type 2 diabetes free of CVRD as of January 1st 2014, was identified and followed-up for 5 years within the French SNDS nationwide claims database. The cumulative incidence of the first occurring CVRD manifestation was estimated using the cumulative incidence function, with death as a competing risk. Cumulative hospitalization costs of each CVRD manifestations were estimated from the perspective of all payers. RESULTS: From 2,079,089 type 2 diabetes without cancer or transplantation, 76.5% were free of CVRD at baseline with a mean age of 65 years, 52% of women and 7% with microvascular complications history. The cumulative incidence of a first CVRD manifestation was 15.3% after 5 years of follow-up with a constant linear increase over time for all CVRD manifestations: The most frequent was CKD representing 40.6% of first occurred CVRD manifestation, followed by HF (23.0%), then PAD (13.5%), stroke (13.2%) and MI (9.7%). HF and CKD together reached about one patient out of ten after 5 years and represented 63.6% of first CVRD manifestations. The 5-year global cost of all CVRD hospitalizations was 3.9 billion euros (B€), i.e. 2,450€ per patient of the whole cohort, with an exponential increase over time for each specific CVRD manifestation. The costliest was CKD (2.0 B€), followed by HF (1.2 B€), then PAD (0.7 B€), stroke (0.6 B€) and MI (0.3 B€). CONCLUSIONS/INTERPRETATION: While MI, stroke and PAD remain classic major risks of complications for CVRD-free type 2 diabetes, HF and CKD nowadays represent individually a higher risk and cost than each of these classic manifestations, and jointly represents a risk and a cost twice as high as these three classic manifestations all together. This should encourage the development of specific HF and CKD preventive strategies.

Patients with stable coronary artery disease and type 2 diabetes but without prior myocardial infarction or stroke and THEMIS-like patients: real-world prevalence and risk of major outcomes from the SNDS French nationwide claims database.

AIM AND HYPOTHESES: The THEMIS randomized trial compared ticagrelor plus aspirin versus placebo plus aspirin for patients with stable coronary artery disease and type 2 diabetes mellitus (CAD-T2DM), and without prior myocardial infarction (MI) or stroke. The aim of the study was to quantify the size of the CAD-T2DM population without prior MI or stroke population in a real-world setting, and more specifically populations with similar THEMIS selection criteria (THEMIS-like and THEMIS-PCI-like populations), as well as their risk of major outcomes in current practice. METHODS: A 2-year follow-up cohort study included all CAD-T2DM without MI/stroke prevalent patients on January 1st, 2014 in the SNDS French nationwide claims database. The THEMIS-like population concerned those ≥ 50 years of age with similar THEMIS inclusion and exclusion criteria. Prevalence was standardized to the European population. The cumulative incidence function was used to estimate the incidence of clinical outcomes (MI, ischemic stroke, and major bleeding according to the TIMI classification) with death as competing risk, and the Kaplan-Meier estimate for all-cause death and a composite outcome of MI, stroke and all-cause death. RESULTS: From a population of about 50 million adults, the prevalence of CAD-T2DM without MI/stroke, THEMIS-like and THEMIS-PCI-like populations was respectively at 6.04, 1.50 and 0.27 per 1000 adults, with a mean age of 72.7, 72.3 and 70.9 years and less comorbidities and diabetic complications for the THEMIS-like and THEMIS-PCI-like population. The 2-year cumulative incidence was respectively 1.7%, 1.3% and 1.6% for MI, 1.7%, 1.5% and 1.4% for stroke, 4.8%, 3.1% and 2.9% for major bleeding, 13.6%, 9.7% and 6.8% for all-cause death, and 16.2%, 12.0% and 9.5% for the composite outcome. CONCLUSION: THEMIS-like prevalence was estimated at 1.50 per 1,000 adults, representing about a quarter of CAD-T2DM without MI/stroke patients, and 0.27 per 1000 adults for the THEMIS-PCI-like populations. In current French practice, the median age of both these populations was about 5-6 years older than in the THEMIS trial, with a 2-year incidence of major outcomes between two or four time above the ones of the placebo arm of the THEMIS trial using very close definitions. Registration No. EUPAS27402 ( http://www.ENCEPP.eu ).

Outcomes and management costs of peripheral arterial disease in France.

BACKGROUND: Little is known about the characteristics and prognosis of patients with peripheral arterial disease (PAD) and related real-life health costs in France. METHODS: A cohort of patients diagnosed with PAD between 2007 and 2011 was extracted from the French Echantillon Généraliste des Bénéficiaires (EGB) claims database. The patients were followed up from the date of PAD diagnosis. Their characteristics, incidence of death and other events, treatments, and costs were analyzed by comparison with age- and gender-matched PAD-free controls. RESULTS: There were 5889 patients with PAD identified. Mean age was 70.8 years, and 68.1% of patients were male. Diabetes was present in 28.9% of patients (13.2% of controls), hypercholesterolemia in 52.9% (28.7%), and hypertension in 46.6% (12.3%); 4.9% of patients had a history of unstable angina or myocardial infarction (0.5%), and 6.0% had a history of stroke or transient ischemic attack (1.4%). At inclusion, 69.3% of patients were receiving antiplatelet drugs (17.3%), 52.3% statins (21.9%), 26.7% angiotensin-converting enzyme inhibitors (13.7%), and 24.2% angiotensin receptor blockers (16.6%). Cumulative mortality rates were 13.2% at 1 year and 19.4% at 2 years (3.2% and 6.5% in controls). Cumulative incidence rates of death and major cardiovascular events (myocardial infarction and ischemic stroke) were 15.7% (95% confidence interval [CI], 14.8%-16.6%) at 1 year and 22.9% (95% CI, 21.9%-24.0%) at 2 years vs 3.9% (95% CI, 3.4%-4.4%) and 7.8% (95% CI, 7.1%-8.5%) in controls. All differences were statistically significant (P < .05). Total annual management costs were €14,949 in the PAD group and €3812 in the control group. CONCLUSIONS: Mortality is elevated and cardiovascular events are frequent among French PAD patients. PAD drug treatment guidelines are not fully implemented in France.

Requests for post-registration studies (PRS), patients follow-up in actual practice: Changes in the role of databases.

Early market access of health products is associated with a larger number of requests for information by the health authorities. Compared with these expectations, the growing expansion of health databases represents an opportunity for responding to questions raised by the authorities. The computerised nature of the health system provides numerous sources of data, and first and foremost medical/administrative databases such as the French National Inter-Scheme Health Insurance Information System (SNIIRAM) database. These databases, although developed for other purposes, have already been used for many years with regard to post-registration studies (PRS). The use thereof will continue to increase with the recent creation of the French National Health Data System (SNDS [2016 health system reform law]). At the same time, other databases are available in France, offering an illustration of "product use under actual practice conditions" by patients and health professionals (cohorts, specific registries, data warehouses, etc.). Based on a preliminary analysis of requests for PRS, approximately two-thirds appeared to have found at least a partial response in existing databases. Using these databases has a number of disadvantages, but also numerous advantages, which are listed. In order to facilitate access and optimise their use, it seemed important to draw up recommendations aiming to facilitate these developments and guarantee the conditions for their technical validity. The recommendations drawn up notably include the need for measures aiming to promote the visibility of research conducted on databases in the field of PRS. Moreover, it seemed worthwhile to promote the interoperability of health data warehouses, to make it possible to match information originating from field studies with information originating from databases, and to develop and share algorithms aiming to identify criteria of interest (proxies). Methodological documents, such as the French National Authority for Health (HAS) recommendations on "Les études post-inscription sur les technologies de santé (médicaments, dispositifs médicaux et actes). Principes et méthodes" [Post-registration studies on health technologies (medicinal products, medical devices and procedures). Principles and methods] should be updated to incorporate these developments.

Outcomes in patients after myocardial infarction similar to those of the PEGASUS-TIMI 54 trial: A cohort study in the French national claims database.

AIMS: The present study aims to describe real-life outcomes in stable patients after-myocardial infarction (MI) similar to those in the PEGASUS-TIMI 54 trial (PEGASUS), which found long-term benefits of ticagrelor in patients with a history of MI. METHODS: One-year event-free post-MI patients were identified in the French claims database representative 1/97 sample (2005-2010) and followed for up to 3 years. A PEGASUS-like (PL) population included patients with age ≥ 65 years, or age ≥ 50 and diabetes, renal dysfunction or prior MI, without stroke, end-stage renal failure or oral anticoagulation. Outcomes were: a composite of all-cause death or hospital admission for MI or stroke; individual events; major bleeding. RESULTS: There were 1585 post-MI patients totalling 3926 person-years including 865 PL patients (2114 PY); 68% were male; mean age was 66 (standard deviation 15) in post-MI, 74 (10) in PL. Outcomes per 100 person-years [95% confidence interval] were, respectively, in post-MI and PL 6.3 [5.6-7.1] and 7.8 [6.7-8.9] for the composite outcome; 5.1 [4.4-5.8] and 6.5 [5.5-7.6] for death; 1.0 [0.7-1.3] and 1.0 [0.6-1.4] for MI; 0.6 [0.4-0.9] and 0.9 [0.5-1.2] for stroke; 1.3 [0.9-1.6] and 1.4 [0.9-1.9] for major bleeding. Event rates were stable over the 3 study years. Placebo patients in the PEGASUS-TIMI54 Study were younger, more often male and had lower event rates, especially for all-cause death and major bleeding. CONCLUSIONS: Patients selected using the criteria described in PEGASUS were older with more comorbidities, resulting in higher all-cause death and bleeding rates, but similar MI recurrence rates.

Prevalence and management of gastroesophageal reflux disease in children and adolescents: a nationwide cross-sectional observational study.

UNLABELLED: This cross-sectional observational study aimed to determine the nationwide prevalence of gastroesophageal reflux disease (GORD) in French children and adolescents. Four hundred four general practitioners and 180 paediatricians compiled a register of all children and adolescents (n = 10,394, aged 0 to 17 years, mean 3.8 ± 5.6 years) who presented over two 3-day periods. For all children who, in the physician's opinion, showed symptoms of gastroesophageal reflux (GOR), a 24-item questionnaire covering the history and management of GOR was completed. Children with symptoms that impaired their daily lives were defined as having GORD, the remainder as having physiological GOR. Of the patients, 15.1 % showed GOR symptoms. Extrapolation to the overall French population yielded a prevalence of 10.3 % for GOR and 6.2 % for GORD. There was a significantly (p < 0.05) greater use of volume reduction or milk thickeners and dorsal positioning among infants with GORD versus physiological GOR. Significantly (p < 0.05) more of the infants and children with GORD received pharmacological therapy. The use of proton pump inhibitors increased with age but was significantly (p < 0.05) higher among those with GORD. CONCLUSIONS: Ten percent of French children and adolescents show GOR symptoms and 6 % have GORD. Clinical presentation and treatment vary in different age groups, but those with GORD are more likely to require pharmacological treatment.

Mortality, Cardiovascular and Limb Events in Patients With Symptomatic Lower Extremity Artery Disease and Diabetes.

The aim of this study was to compare the prognosis of patients according to diabetes status, during a 1-year follow-up after hospital admission for lower extremity artery disease, in the prospective COPART (COhorte de Patients ARTériopathes) registry. Inclusion criteria were intermittent claudication, ischemic rest pain, tissue loss, or acute limb ischemia, with radiological and hemodynamic confirmation. Among 2494 patients, 1235 (49.5%) had diabetes. Incidence rates for major adverse cardiovascular events (MACE) were 18.0/100 person-years (95% confidence interval [CI], 15.4-21.0) for the diabetes group and 11.1/100 person-years (95% CI, 9.2-13.4) for the non-diabetes group. Incidence rates of all-cause mortality were 29.8/100 person-years (95% CI, 26.5-33.4) for the diabetes group and 19.7/100 person-years (95% CI, 17.2-22.7) for the non-diabetes group. Incidence rates of major limb amputation were 24.2/100 person-years (95% CI, 21.1-27.8) for the diabetes group and 11.6/100 person-years (95% CI, 9.6-14.0) for the non-diabetes group. Diabetes was associated with MACE, adjusted hazard ratio 1.60 (95% CI, 1.16-2.22), and all-cause mortality, unadjusted HR 1.49 (95% CI, 1.24-1.78). In the multivariate analysis, diabetes was no longer associated with major amputation, adjusted HR 1.15 (95% CI, .87-1.51). Patients hospitalized for LEAD with diabetes had a higher risk of MACE than those without diabetes.

Secondary prevention of acute coronary events with antiplatelet agents (SPACE-AA): One-year real-world effectiveness and safety cohort study in the French nationwide claims database.

BACKGROUND AND AIMS: We aimed to compare the effectiveness of ticagrelor vs. clopidogrel or prasugrel on recurrence of acute coronary syndromes (ACS) in real-life conditions, as requested by regulatory authorities at the time of marketing. METHODS: We performed a cohort study in SNDS, the French national healthcare database. All patients with a hospital admission for ACS in 2013 were followed one year. Patients on ticagrelor, clopidogrel or prasugrel were matched 1:1 using age, gender, index ACS type, and high-dimensional propensity scores (hdPS). Outcomes were ACS, stroke, all-cause death, and major bleeding, compared within matched groups using Cox proportional hazards models analysis during treatment. RESULTS: 54,048 ACS were hospitalized in 2013. At discharge, 19,796 were dispensed clopidogrel, 8242 prasugrel, and 13,916 ticagrelor. Per group, 9224 ticagrelor vs. clopidogrel, 6752 ticagrelor vs. prasugrel, and 4676 prasugrel vs. clopidogrel patients were matched. Compared to clopidogrel, ticagrelor was associated with a lower hazard ratio of death 0.73 [0.59-0.90] and composite criterion (0.88, 95% CI [0.79-0.99] but not ACS 0.92 [0.80-1.06], stroke (0.96 [017-5.53]) or major bleeding (1.02 [0.82-1.26]). Prasugrel was not different from ticagrelor or clopidogrel for any outcome, in matched patients. CONCLUSIONS: Ticagrelor in real-life conditions in matched populations was associated with a lower risk of all-cause death than clopidogrel, and a lower risk of composite outcome, as in the main pivotal clinical trial. Ticagrelor and prasugrel were not different, nor were prasugrel and clopidogrel.

The Use of Saxagliptin in People with Type 2 Diabetes in France: The Diapazon Epidemiological Study.

INTRODUCTION: Saxagliptin is a potent, reversible inhibitor of dipeptidyl peptidase-4 that is indicated for the treatment of type 2 diabetes. The DIAPAZON study was a multicenter observational study intended to document the effectiveness, safety and patterns of saxagliptin use in France, including the saxagliptin retention rate, over 2 years of follow-up. METHODS: A geographically representative sample of 304 French physicians (general practitioners and specialist endocrinologists or diabetologists) recruited 1131 adults with type 2 diabetes into an ambispective cohort; 1033 fulfilled the inclusion criteria. All had started saxagliptin during the previous 6 months or at study inclusion, and follow-up was for 24 ± 3 months after starting saxagliptin. RESULTS: The mean age of the study population when starting saxagliptin was 61 years, and the mean HbA1c level was 8.0%; 79% had an HbA1c level ≥7%. Prior to starting saxagliptin treatment, most participants (91%) were receiving treatment with oral glucose-lowering drugs alone. The most commonly prescribed regimen at starting saxagliptin (53% of participants) was a combination of saxagliptin and metformin. The overall saxagliptin retention rate at 2 years was 79%, as estimated by the Kaplan-Meier method. The most common reasons for discontinuation were inadequate glycemic control (52%) and intolerance (22%). During the course of the study, the mean HbA1c level decreased to 7.0%, and the percentage of people with HbA1c <7% increased from 21% to 49%. The mean change in body weight was -1.8 kg. A total of 294 hypoglycemic episodes were reported in 70 participants (6.8%) during the follow-up period. Of these, 143 episodes in 41 participants (4.0%) occurred when saxagliptin was used in combination with agents associated with hypoglycemia, such as insulin, sulfonylureas or glinides. CONCLUSION: Saxagliptin is efficacious and well tolerated in a real-world practice setting, with almost 80% of participants remaining on treatment after 2 years. FUNDING: AstraZeneca, France.

Using big data from health records from four countries to evaluate chronic disease outcomes: a study in 114 364 survivors of myocardial infarction.

AIMS: To assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors. METHODS AND RESULTS: We used samples of national, ongoing, unselected record sources to assess three outcomes: cause death; a composite of myocardial infarction (MI), stroke, and all-cause death; and hospitalized bleeding. Patients aged 65 years and older entered the study 1 year following the most recent discharge for acute MI in 2002-11 [n = 54 841 (Sweden), 53 909 (USA), 4653 (England), and 961 (France)]. Across each of the four countries, we found consistent associations with 12 baseline prognostic factors and each of the three outcomes. In each country, we observed high 3-year crude cumulative risks of all-cause death (from 19.6% [England] to 30.2% [USA]); the composite of MI, stroke, or death [from 26.0% (France) to 36.2% (USA)]; and hospitalized bleeding [from 3.1% (France) to 5.3% (USA)]. After adjustments for baseline risk factors, risks were similar across all countries [relative risks (RRs) compared with Sweden not statistically significant], but higher in the USA for all-cause death [RR USA vs. Sweden, 1.14 (95% confidence interval 1.04-1.26)] and hospitalized bleeding [RR USA vs. Sweden, 1.54 (1.21-1.96)]. CONCLUSION: The validity of using hospital record data is supported by the consistency of estimates across four countries of a high adjusted risk of death, further MI, and stroke in the chronic phase after MI. The possibility that adjusted risks of mortality and bleeding are higher in the USA warrants further study.

Assessment of cardiovascular risk in primary care patients in France.

BACKGROUND: Current guidelines for the prevention of cardiovascular disease emphasize the importance of assessing global cardiovascular risk, but there is evidence that risk is often assessed inaccurately. AIMS: To compare general practitioner-reported global cardiovascular risk in French primary care patients with estimates based on established risk-scoring systems, and to identify factors accounting for any mismatch between the analyses. METHODS: Data on patients, aged 50 years or older, seen during two 3-day periods were provided by 619 general practitioners. Physicians rated each patient's cardiovascular risk as low, moderate or high, according to their perception; in addition, risk was assessed using the Framingham and Systematic coronary risk evaluation (SCORE) risk-scoring systems. RESULTS: A total of 13,446 patients aged greater or equal to 50 years were included. Of 11,241 patients with no previous history of cardiovascular disease, 47% were considered by their physicians to be at low risk of cardiovascular disease and 14% to be at high risk. In that population, 72% of patients rated as high risk according to the Framingham system and 77% rated as high risk according to SCORE system were incorrectly assessed by their physicians; similar results were observed in patient cohorts based on whether or not patients had received treatment for dyslipidaemia. Weighted kappa analysis showed poor agreement between physician risk assessment and both the Framingham and SCORE risk-scoring systems. CONCLUSION: This study underlines the mismatch between GP-estimated cardiovascular risk and the risk assessed using scoring systems, especially for high-risk patients.