Patrick Blin

Introduction Antiplatelet therapy with low-dose aspirin, alone or as dual antiplatelet therapy (DAPT) with a P2Y₁₂ inhibitor, is used in secondary prevention following myocardial infarction (MI). However, the optimal duration of DAPT is unknown. Methods This cohort study performed in the French nationwide claims database compared 3-year outcomes between DAPT and low-dose aspirin alone pursued beyond 1 year after MI. All adults discharged from hospital following MI in 2013–2014, and who survived ≥ 1 year under DAPT, without rehospitalization for acute coronary syndrome or major bleeding were enrolled (N = 51,468). The primary outcome was a composite of MI, stroke, major bleeding, or all-cause death during the 3 years following the index date (defined as 365 days after MI). Secondary outcomes were a composite of MI, stroke, and all-cause death, and each component of the primary composite. DAPT and low-dose aspirin exposure periods were analyzed as time-dependent variables and compared using hazard ratios (HR) from Cox proportional hazard or Fine–Gray competing risks models, adjusted using a high-dimensional disease risk score. Results The 3-year cumulative follow-up duration was 93,398 person-years (DAPT exposure: 26,223 person-years; low-dose aspirin exposure: 67,175 person-years). HRs for DAPT versus low-dose aspirin were 0.93 (0.85–1.03) for the primary composite outcome, 0.93 (0.84–1.03) for the secondary composite outcome, 1.04 (0.87–1.25) for MI, 0.91 (0.70–1.17) for stroke, 1.19 (0.88–1.60) for major bleeding, and 0.94 (0.83–1.07) for death. Conclusions This national cohort study did not find a significant benefit of continued DAPT beyond 1 year after MI compared with low-dose aspirin. Registration This study was registered with the European Medicines Agency EUPASS registry (https://catalogues.ema.europa.eu/catalogue-rwd-studies; registration no. EUPAS29177). Graphical Abstract

Purpose: This paper aims to introduce an algorithm designed to identify Venous Thromboembolism (VTE) in the French National Healthcare Database (SNDS) and to estimate its positive predictive value.Methods: A case‐identifying algorithm was designed using SNDS inpatient and outpatient encounters, including hospital stays with discharge diagnoses, imaging procedures and drugs dispensed, of French patients aged at least 18 years old to whom baricitinib or Tumor Necrosis Factor Inhibitors (TNFi) were dispensed between September 1, 2017, and December 31, 2018. An intra‐database validation study was then conducted, drawing 150 cases identified as VTE by the algorithm and requesting four vascular specialists to assess them. Patient profiles used to conduct the case adjudication were reconstituted from de‐identified pooled and formatted SNDS data (i.e., reconstituted electronic health records—rEHR) with a 6‐month look‐back period prior to the supposed VTE onset and a 12‐month follow‐up period after. The positive predictive value (PPV) with its 95% confidence interval (95% CI) was calculated as the number of expert‐confirmed VTE divided by the number of algorithm‐identified VTE. The PPV and its 95% CI were then recomputed among the same patient set initially drawn, once the VTE‐identifying algorithm was updated based on expert recommendation.Results: For the 150 patients identified with the first VTE‐identifying algorithm, the adjudication committee confirmed 92 cases, resulting in a PPV of 61% (95% CI = [54–69]). The final VTE‐identifying algorithm including expert suggestions showed a PPV of 92% (95% CI = [86–98]) with a total of 87 algorithm‐identified cases, including 80 retrieved from the 92 confirmed by experts.Conclusion: The identification of VTE in the SNDS is possible with a good PPV.

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.

Background Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal disease (CVRD) manifestations for type 2 diabetes. The incidence of the first occurring CVRD manifestation and cumulative hospitalization costs of each CVRD manifestation are not well known 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 about 2 million 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 of these three classic manifestations all together. This should encourage the development of specific HF and CKD preventive strategies.

Purpose: The objective was to compare the risk of malignancies in real‐world settings between exclusive immunosuppressant (IS) and immunomodulator (IM) use in multiple sclerosis (MS).Methods: A nested case–control study was designed within a new‐user cohort of all patients with MS who initiated a first IM or IS between 2008 and 2014, and without cancer history, using the information of the SNDS nationwide French claims database. Incident cancer cases were matched with up to six controls on year of birth, sex, initiation date, and disease risk score of cancer. A conditional logistic regression (odds ratio [95% confidence interval]) was used to compare exclusive IS versus IM use during follow‐up and according to three use durations.Results: From 28 720 newly treated patients with MS, 407 incident cancers were observed during the follow‐up with 2324 matched controls. A significant increase in cancer risk was observed for IS compared with IM (1.36 [1.05, 1.77]), with similar increases for the first 2 years of use but not for ≥2 years (1.06 [0.65, 1.75]). Similar increase was also observed for IS with indications other than MS (1.37 [1.04, 1.81]) but not for IS indicated only in MS (1.03 [0.45, 2.34]).Conclusions: Compared with IM, a 37% increase in cancer risk was observed for IS with indications other than MS and used for a short duration (≤2 years) but not for IS indicated only in MS. The absence of risk for prolonged exposure of IS with indications other than MS is not in favor of a causal relation with these drugs.

Background: Healthcare pathways of patients with prostate cancer are heterogeneous and complex to apprehend using traditional descriptive statistics. Clustering and visualization methods can enhance their characterization.Methods: Patients with prostate cancer in 2014 were identified in the French National Healthcare database (Système National des Données de Santé—SNDS) and their data were extracted with up to 5 years of history and 4 years of follow‐up. Fifty‐one‐specific encounters constitutive of prostate cancer management were synthesized into four macro‐variables using a clustering approach. Their values over patient follow‐ups constituted healthcare pathways. Optimal matching was applied to calculate distances between pathways. Partitioning around medoids was then used to define consistent groups across four exclusive cohorts of incident prostate cancer patients: Hormone‐sensitive (HSPC), metastatic hormone‐sensitive (mHSPC), castration‐resistant (CRPC), and metastatic castration‐resistant (mCRPC). Index plots were used to represent pathways clusters.Results: The repartition of macro‐variables values—surveillance, local treatment, androgenic deprivation, and advanced treatment—appeared to be consistent with prostate cancer status. Two to five clusters of healthcare pathways were observed in each of the different cohorts, corresponding for most of them to relevant clinical patterns, although some heterogeneity remained. For instance, clustering allowed to distinguish patients undergoing active surveillance, or treated according to cancer progression risk in HSPC, and patients receiving treatment for potentially curative or palliative purposes in mHSPC and mCRPC.Conclusion: Visualization methods combined with a clustering approach enabled the identification of clinically relevant patterns of prostate cancer management. Characterization of these care pathways is an essential element for the comprehension and the robust assessment of healthcare technology effectiveness.

To conduct the direct comparison of abiraterone acetate and docetaxel for first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) in real-life settings.Data were extracted f...

Background and purpose: Studies have not yet found conclusive results on the risk of cancer in patients with multiple sclerosis (MS). This study aimed to compare the incidence of all cancers and of specific types of cancer between MS patients and the general population by age and by sex.Methods: All prevalent MS patients identified between 2008 and 2014 in the nationwide French health care database (Système National des Données de Santé) and without history of malignancy were included in a cohort study and followed up until cancer occurrence, date of death, or 31 December 2015, whichever came first. MS patients were matched based on sex and year of birth to non‐MS controls from the general population without cancer before index date. Incidence rate was reported per 100,000 person‐years (PY), and risk of cancer was estimated by type of cancer, age, and sex using a Cox model (hazard ratio [HR] and its 95% confidence interval [CI]).Results: Overall, 576 cancers per 100,000 PY were observed in MS patients versus 424 per 100,000 PY in the control population. The risk of cancer was higher among MS patients than among population controls whether considered overall (HR = 1.36, 95% CI = 1.29–1.43) or for prostate (HR = 2.08, 95% CI = 1.68–2.58), colorectal and anal (HR = 1.35, 95% CI = 1.16–1.58), trachea, bronchus, and lung (HR = 2.36, 95% CI = 1.96–2.84), and to a lesser extent, breast cancer (HR = 1.12, 95% CI = 1.03–1.23).Conclusions: MS patients were associated with increased risk of cancer compared to population controls.