Michel Cucherat

Hospices Civils de Lyon, Lyons, Rhône-Alpes, France

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Publications (187)671.67 Total impact

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    ABSTRACT: Anticoagulant thromboprophylaxis with low molecular weight heparin is widely used in nonsurgical settings. To obtain best estimates of the effects of nadroparin for the prevention of venous thromboembolism (VTE) in nonsurgical patients, we conducted a systematic review and meta-analysis. Data sources were Medline, Embase, and Cochrane Library supplemented with conference abstracts, without language restrictions. Selection criteria were randomized controlled trials with nadroparin at prophylactic dose in adult nonsurgical patients. Main efficacy outcomes were major VTE (the composite of symptomatic deep vein thrombosis, symptomatic pulmonary embolism, asymptomatic proximal deep vein thrombosis and VTE-related death) and symptomatic VTE. The main safety outcome was major bleeding. We expressed treatment effects as risk ratios. Ten studies (4 vs. placebo or no treatment, 4 vs. UFH, 1 vs. fondaparinux and 1 vs. warfarin) enrolling a total of 7658 patients were included. In comparison with placebo, nadroparin reduced major VTE by about one-half (RR 0.48, 95% CI 0.24-0.97) with a consistent effect on symptomatic VTE (RR 0.69, 95% CI 0.46-1.05) and no increase in major bleeding (RR 1.51, 95% CI 0.40-5.79). In comparison with other pharmacological prophylaxis, nadroparin was similarly efficacious for prevention of major VTE (RR 1.14, 95% CI 0.63-2.10) and symptomatic VTE (RR 1.10, 95% CI 0.51-2.35) and produced similar effects on major bleeding (RR 0.60, 95% CI 0.25-1.50). Five studies were open label, and for three of these the adjudication method was not described or not blinded. In nonsurgical populations at risk of VTE, nadroparin reduced VTE by about one half compared with placebo or no treatment and appeared similarly effective and safe as other prophylactic anticoagulants.
    No preview · Article · Oct 2015 · Journal of Thrombosis and Thrombolysis
  • François Gueyffier · Michel Cucherat

    No preview · Article · Sep 2015 · Journal of Hypertension
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    ABSTRACT: Our main objective was to see whether the therapeutic benefit observed in placebo controlled RCTs is different between adults and children. We searched three electronic databases for meta-analyses that included double-blind, placebo-controlled RCTs with separate results for adults and children. The selected reviews were classified according to disease and drug used. The heterogeneity of treatment response between adults and children was measured using ratio of odds ratios (RORs). We selected 89 meta-analyses and calculated RORs for 124 drugs. Heterogeneity in the direction of the treatment effect was observed in one drug and heterogeneity in the quantity of the treatment effect in 13 drugs. Indicating significantly different treatment effect in adults when compared with children. RORs were not significantly different from 1 for 110 drugs. For 36 of these drugs, the treatment effect was confirmed in both populations. We found different treatment benefits estimated by clinical trials performed in adults compared with those performed in children for 14 out of 124 drugs. Data on dose adjustment and child age groups from RCTs were not adequately reported in order to investigate their influence on the treatment benefit dissimilarities. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · Journal of clinical epidemiology
  • C. Chapelle · P. Mismetti · M. Cucherat · S. Laporte

    No preview · Article · May 2015 · Revue d Épidémiologie et de Santé Publique

  • No preview · Article · May 2015
  • Michel Cucherat · Silvy Laporte

    No preview · Article · Jan 2015 · Correspondances en MHND
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    ABSTRACT: Objective To investigate the effect of pretreatment with P2Y12 receptor inhibitors compared with no pretreatment on efficacy and safety of treatment of non-ST elevation acute coronary syndrome (ACS). Data sources Two reviewers independently searched Medline, Embase, Cochrane Controlled Trials, and BioMed Central databases for randomized placebo controlled trials and observational studies from August 2001 to March 2014. Study eligibility Studies must have reported both all-cause mortality (primary efficacy endpoint) and major bleeding (safety endpoint) outcomes. Data extraction Data on sample size, characteristics, drug dose and delay of administration, and outcomes were independently extracted and analyzed. Data synthesis A random-effect model was applied. The analysis was performed (i) in all patients independently of the management strategy and (ii) only in patients undergoing percutaneous coronary intervention. Results Of the 393 titles identified, seven (four randomized controlled trials, one observational analysis from a randomized controlled trial, and three observational studies) met the inclusion criteria. No study was identified for ticagrelor or cangrelor, and analyses were thus limited to thienopyridines. A total of 32 383 non-ST elevation ACS patients were included, 18 711 coming from randomized controlled trials. Of these, 55% underwent percutaneous coronary intervention (PCI). Pretreatment was not associated with a significant lower risk of mortality in all patients (odds ratio 0.90 (95% confidence interval 0.75 to 1.07), P=0.24), in particular when considering only the randomized controlled trials (odds ratio 0.90 (0.71 to 1.14), P=0.39). Similar results were observed in the cohort of patients undergoing PCI. A significant 30-45% excess of major bleeding was consistently observed in all patients (odds ratio 1.32 (1.16 to 1.49), P<0.0001) and in those undergoing PCI, as well as in the subset analyses of randomized controlled trials of these two cohorts of patients. There was a reduction in major adverse cardiovascular events in the analysis of all patients (odds ratio 0.84 (0.72 to 0.98), P=0.02), driven by the old clopidogrel studies (CURE and CREDO), but the difference was not significant for the cohort of patients undergoing PCI. Stent thrombosis, stroke, and urgent revascularization did not differ between groups (pretreatment v no pretreatment). The results were consistent for both thienopyridines and confirmed in sensitivity analyses. Limitations Analysis was not performed on individual patient’s data. Conclusion In patients presenting with non-ST elevation ACS, pretreatment with thienopyridines is associated with no significant reduction of mortality but with a significant excess of major bleeding no matter the strategy adopted, invasive or not. Our results do not support a strategy of routine pretreatment in patients with non-ST elevation ACS.
    Full-text · Article · Oct 2014 · BMJ Clinical Research

  • No preview · Article · Aug 2014 · Revue d Épidémiologie et de Santé Publique
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    ABSTRACT: Two enoxaparin dosage regimens are used as comparators to evaluate new anticoagulants for thromboprophylaxis in patients undergoing major orthopaedic surgery, but so far no satisfactory direct comparison between them has been published. Our objective was to compare the efficacy and safety of enoxaparin 3,000 anti-Xa IU twice daily and enoxaparin 4,000 anti-Xa IU once daily in this clinical setting by indirect comparison meta-analysis, using Bucher's method. We selected randomised controlled trials comparing another anticoagulant, placebo (or no treatment) with either enoxaparin regimen for venous thromboembolism prophylaxis after hip or knee replacement or hip fracture surgery, provided that the second regimen was assessed elsewhere versusthe same comparator. Two authors independently evaluated study eligibility, extracted the data, and assessed the risk of bias. The primary efficacy outcome was the incidence of venous thomboembolism. The main safety outcome was the incidence of major bleeding. Overall, 44 randomised comparisons in 56,423 patients were selected, 35 being double-blind (54,117 patients). Compared with enoxaparin 4,000 anti-Xa IU once daily, enoxaparin 3,000 anti-Xa IU twice daily was associated with a reduced risk of venous thromboembolism (relative risk [RR]: 0.53, 95% confidence interval [CI]: 0.40 to 0.69), but an increased risk of major bleeding (RR: 2.01, 95% CI: 1.23 to 3.29). In conclusion, when interpreting the benefit-risk ratio of new anticoagulant drugs versus enoxaparin for thromboprophylaxis after major orthopaedic surgery, the apparently greater efficacy but higher bleeding risk of the twice-daily 3,000 anti-Xa IU enoxaparin regimen compared to the once-daily 4,000 anti-Xa IU regimen should be taken into account.
    Full-text · Article · Jun 2014 · Thrombosis and Haemostasis
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    ABSTRACT: To assess the efficacy of low-molecular-weight heparin (LMWH) venous thromboprophylaxis in patients with transient reduced mobility in the non-major orthopaedic setting. A meta-analysis was conducted using data from all available randomized trials comparing LMWH with placebo or no prophylactic treatment in patients with leg immobilization for fracture or soft-tissue injury of the lower limb or in patients undergoing knee arthroscopy. The primary endpoint was the incidence of major venous thromboembolic events (VTEs), including asymptomatic proximal deep-vein thrombosis, symptomatic VTEs, and VTE-related death. The Mantel-Haenszel method was used to generate the summary statistics for the overall effect of LMWH. Fourteen studies were included (4,726 patients). The weighted rate of major VTEs was estimated to be 2.9% (95% confidence interval [CI], 2.2% to 3.7%) without LMWH prophylaxis. Overall, a significant 68% reduction in the risk of major VTEs was observed with LMWH prophylaxis (relative risk [RR], 0.32; 95% CI, 0.20 to 0.51; P < .001). The treatment effect was not modified by the clinical setting, that is, distal lower limb injury (7 studies; 1,711 patients; RR, 0.42; 95% CI, 0.20 to 0.86) or knee arthroscopy (6 studies; 2,428 patients; RR, 0.27; 95% CI, 0.15 to 0.49). A nonsignificant 35% increase in the risk of major bleeding was observed in the LMWH prophylaxis group (RR, 1.35; 95% CI, 0.53 to 3.47). This meta-analysis indicates potential efficacy of LMWH in preventing thromboembolic events in patients with reduced mobility in the non-major orthopaedic setting compared with placebo or no treatment. However, the decision of whether to implement LMWH prophylaxis in each specific setting should also take into account the risk of VTEs in the absence of prophylaxis, the potential adverse effects of LMWH, and the cost. Level II, meta-analysis of Level II studies or Level I studies with inconsistent results.
    Full-text · Article · May 2014 · Arthroscopy The Journal of Arthroscopic and Related Surgery
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    ABSTRACT: The well-known limitations of vitamin K antagonists (VKA) led to development of new oral anticoagulants (NOAC) in non-valvular atrial fibrillation (NVAF). The aim of this meta-analysis was to determine the consistency of treatment effects of NOAC irrespective of age, comorbidities, or prior VKA exposure. All randomized, controlled phase III trials comparing NOAC to VKA up to October 2012 were eligible provided their results (stroke/systemic embolism (SSE) and major bleeding (MB)) were reported according to age (≤ or >75 years), renal function, CHADS2 score, presence of diabetes mellitus or heart failure, prior VKA use or previous cerebrovascular events. Interactions were considered significant at p <0.05. Three studies (50,578 patients) were included, respectively evaluating apixaban, rivaroxaban, and dabigatran versus warfarin. A trend towards interaction with heart failure (p = 0.08) was observed with respect to SSE reduction, this being greater in patients not presenting heart failure (RR = 0.76 [0.67-0.86]) than in those with heart failure (RR = 0.90 [0.78-1.04]); Significant interaction (p = 0.01) with CHADS2 score was observed, NOAC achieving a greater reduction in bleeding risk in patients with a score of 0-1 (RR 0.67 CI 0.57-0.79) than in those with a score ≥2 (RR 0.85 CI 0.74-0.98). Comparison of MB in patients with (RR 0.97 CI 0.79-1.18) and without (RR 0.76 CI 0.65-0.88) diabetes mellitus showed a similar trend (p = 0.06). No other interactions were found. All subgroups derived benefit from NOA in terms of SSE or MB reduction. NOAC appeared to be more effective and safer than VKA in reducing SSE or MB irrespective of patient comorbidities. Thromboembolism risk, evaluated by CHADS2 score and, to a lesser extent, diabetes mellitus modified the treatment effects of NOAC without complete loss of benefit with respect to MB reduction.
    Full-text · Article · Mar 2014 · PLoS ONE
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    ABSTRACT: To date no network meta-analysis (NMA) has accounted for baseline variations in viral load when assessing the relative efficacy of interventions for chronic hepatitis B (CHB). We undertook baseline-adjusted and unadjusted analyses using the same data to explore the impact of baseline viral load (BVL) on CHB treatment response. We searched Embase, Medline, Medline in Process and the Cochrane CENTRAL databases for randomised clinical trials (RCTs) of monotherapy interventions at licensed doses for use in CHB. Search strategies comprised CHB disease and drug terms (a combination of controlled vocabulary and free text terms) and also a bespoke RCT filter.The NMA was undertaken in WinBUGs using fixed and random effects methods, using data obtained from a systematic review. Individual patient data (IPD) from an entecavir clinical trial were used to quantify the impact of different baseline characteristics (in particular undetectable viral load (UVL) at 1 year) on relative treatment effect. Study level mean baseline values from all identified studies were used. Results were generated for UVL and presented as relative risks (RRs) and 95% credible intervals (CrIs) using entecavir as reference treatment. Overall, for all eight relevant interventions we identified 3,000 abstracts. Following full text review a total of 35 (including the contents of six clinical study reports) met the inclusion critera; 19 were in hepatitis B e antigen (HBeAg)-positive patients and 14 of the 19 contained outcome information of relevance to the NMA.Entecavir and tenofovir studies had heterogeneous patient populations in terms of BVL (mean values 9.29 and 8.65 log10 copies/ml respectively). After adjusting UVL for BVL using an informative prior based on the IPD analysis, the difference between entecavir and tenofovir was not statistically significant (RR 1.27, 95% CrI 0.96 to 1.47 - fixed effects). A similar conclusion was found in all sensitivity analyses. Adjusted tenofovir results were more consistent with observed clinical trial response rates. This study demonstrates the importance of adjusting for BVL when assessing the relative efficacy of CHB interventions in achieving UVL. This has implications for both clinical and economic decision making.
    Full-text · Article · Mar 2014 · Systematic Reviews
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    ABSTRACT: Introduction.– Les essais randomisés en ouvert avec évaluation à l’aveugle (PROBE) permettent de limiter les biais d’évaluation par rapport aux études en ouvert simple, et sont parfois considérés comme aussi performants que les essais en double insu pour l’évaluation d’une stratégie thérapeutique. Cependant, si l’exagération de l’effet traitement liée aux études en ouvert est bien estimée, celle liée aux études PROBE n’a jamais été estimée. Nous avons cherché à quantifier le biais d’estimation lié au schéma d’études PROBE par rapport aux études en double insu à partir des essais évaluant un nouvel anticoagulant oral dans la fibrillation atriale. Me´thodes.– Tous les essais randomisés évaluant un nouvel anticoagulant par rapport au traitement de référence (anti-vitamine K) dans la prévention des événements emboliques dans la fibrillation atriale ont été inclus. Les bases de données consultées étaient MEDLINE, EMBASE, la library Cochrane, les sites web de l’ « US National Institute of Health, Meta-Embol » et les registres d’essais cliniques. Le critère principal d’évaluation et les critères secondaires étaient communs à toutes les études : accidents vasculaires cérébraux et embolies systémiques (AVC-ES), AVC hémorragiques, hémorragies majeures, hémorragies intracrâniennes, et mortalité cardiovas- culaire. L’effet traitement commun a été estimé pour les études PROBE et pour les études en double insu en combinant le logarithme des risques relatifs (RR) de chacune des études pondéré par l’inverse de la variance, selon un modèle à effets fixes ou à effets aléatoires. L’exagération de l’effet traitement a été estimée par le rapport des effets communs entre les études PROBE et les études en double insu ; le test d’interaction a été considéré comme significatif au seuil de 0,10. Re´sultats.– Au total, 8 études (59 238 patients) ayant comparé l’apixaban, l’edoxaban, le dabigatran, l’AZD0837, le ximelagatran, ou le rivaroxaban aux anti-vitamine K ont été incluses. De fac¸on globale, une réduction significative est observée avec les nouveaux anticoagulants oraux sur le critère principal AVC-ES (RR = 0,84 ; IC95 % 0,76–0,92) ainsi que sur tous les autres critères. L’estimation de l’efficacité des nouveaux anticoagulants oraux sur le critère primaire était plus importante à partir des études PROBE (5 essais, 22 947 patients ; RR = 0,76, IC95 % 0,65–0,90) comparé aux études en double insu (3 essais, 36 387 patients ; RR = 0,88, IC95 % 0,78–0,98), soit une majoration non significative de 16 % (test d’interaction p = 0,17). L’interaction était évidente pour les AVC hémorragiques (test d’interaction p = 0,05) avec une majoration de 72 % de l’effet traitement dans les études PROBE (RR = 0,32 ; IC95 % 0,20–0,49) par rapport études en double insu (RR = 0,55 ; IC95 % 0,41–0,73). Aucune autre interaction n’a été significative sur les autres critères. Conclusions.– Les études PROBE peuvent influencer les résultats d’un essai clinique en faveur du nouveau traitement. Cependant, l’influence d’un facteur confondant comme la classe pharmacologique ne peut être exclue. L’étude avec l’edoxaban dont le suivi est en cours, devrait permettre d’affiner les estimations. Il s’agit de rester prudent lors des comparaisons indirectes de ces molécules entre elles lors des méta-analyses en réseau.
    No preview · Article · Feb 2014 · Revue d Épidémiologie et de Santé Publique

  • No preview · Article · Feb 2014 · Revue d Épidémiologie et de Santé Publique
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    ABSTRACT: Purpose To assess the efficacy of low-molecular-weight heparin (LMWH) venous thromboprophylaxis in patients with transient reduced mobility in the non-major orthopaedic setting. Methods A meta-analysis was conducted using data from all available randomized trials comparing LMWH with placebo or no prophylactic treatment in patients with leg immobilization for fracture or soft-tissue injury of the lower limb or in patients undergoing knee arthroscopy. The primary endpoint was the incidence of major venous thromboembolic events (VTEs), including asymptomatic proximal deep-vein thrombosis, symptomatic VTEs, and VTE-related death. The Mantel-Haenszel method was used to generate the summary statistics for the overall effect of LMWH. Results Fourteen studies were included (4,726 patients). The weighted rate of major VTEs was estimated to be 2.9% (95% confidence interval [CI], 2.2% to 3.7%) without LMWH prophylaxis. Overall, a significant 68% reduction in the risk of major VTEs was observed with LMWH prophylaxis (relative risk [RR], 0.32; 95% CI, 0.20 to 0.51; P < .001). The treatment effect was not modified by the clinical setting, that is, distal lower limb injury (7 studies; 1,711 patients; RR, 0.42; 95% CI, 0.20 to 0.86) or knee arthroscopy (6 studies; 2,428 patients; RR, 0.27; 95% CI, 0.15 to 0.49). A nonsignificant 35% increase in the risk of major bleeding was observed in the LMWH prophylaxis group (RR, 1.35; 95% CI, 0.53 to 3.47). Conclusions This meta-analysis indicates potential efficacy of LMWH in preventing thromboembolic events in patients with reduced mobility in the non-major orthopaedic setting compared with placebo or no treatment. However, the decision of whether to implement LMWH prophylaxis in each specific setting should also take into account the risk of VTEs in the absence of prophylaxis, the potential adverse effects of LMWH, and the cost. Level of Evidence Level II, meta-analysis of Level II studies or Level I studies with inconsistent results.
    Full-text · Article · Jan 2014 · Arthroscopy The Journal of Arthroscopic and Related Surgery
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    Full-text · Article · Oct 2013 · Journal of the American College of Cardiology
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    Full-text · Article · Oct 2013 · Journal of the American College of Cardiology
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    ABSTRACT: Purpose: Although Clopidogrel pretreatment is recommended for Acute Coronary Syndrome (ACS) and stable coronary patients scheduled for Percutaneous Coronary Intervention (PCI), the benefit of this strategy compared to an administration at the time of PCI has not been shown on hard clinical outcome. In this new analysis, we performed a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) and registries to evaluate the impact of clopidogrel pretreatment on mortality, MACE and major bleeding after PCI, as compared with no pretreatment. Methods: We included studies from MEDLINE, EMBASE, Cochrane Controlled Trials Register databases and references lists of qualifying articles that reported clinical data on mortality and major bleeding. A random-effect model was applied. Pretreatment was defined as the administration of clopidogrel before PCI or catheterization. The primary efficacy and safety endpoints were all-cause mortality and major bleeding, respectively. Results: Of the 392 titles identified, 15 articles met the inclusion criteria, published between August 2001 and September 2012, including 37 914 patients: 13 628 patients with stable coronary artery disease (CAD), 15 650 with Non ST Elevation ACS (NSTE ACS) and 8 536 with ST elevation ACS (STEMI) presentation. Results for Death, Major Bleeding and MACE are shown in Figure I.
    Full-text · Article · Oct 2013 · Journal of the American College of Cardiology
  • S. Laporte · M. Cucherat

    No preview · Article · Oct 2013
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    ABSTRACT: Open-label, randomized controlled trials (RCTs) are subject to observer bias. If patient management is conducted without blinding, a difference between groups may be explained by other factors than study treatment. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. In type 2 diabetes, some antihypertensive or lipid-lowering drugs are effective against diabetic complications. We wanted to determine if these concomitant treatments were correctly reported in articles of RCTs on type 2 diabetes and if they might have influenced the outcome. We performed a systematic review using Medline, Embase, and the Cochrane Library (from January 1950 to July 2010). Open-label RCTs assessing the effectiveness of intensive blood-glucose control in type 2 diabetes were included. We chose five therapeutic classes with proven efficacy against diabetes complications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs), fibrates, statins, and aspirin. Differences between concomitant treatments were considered statistically significant when p < 0.05. A total of eight open-label RCTs were included, but only three (37.5%) of them published concomitant treatments. In two studies (ACCORD and ADVANCE), a statistically significant difference was observed between the two groups for aspirin (p = 0.02) and ACEIs (p = 0.02). Few concomitant treatments were published in this sample of open-label RCTs. We cannot completely eliminate an observer bias for these studies. This bias probably influenced the results to an extent that has yet to be determined.
    Full-text · Article · Aug 2013 · BMC Medical Research Methodology

Publication Stats

6k Citations
671.67 Total Impact Points

Institutions

  • 1998-2015
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2000-2014
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 1996-2014
    • Claude Bernard University Lyon 1
      • • Filière de gynécologie-obstétrique
      • • Laboratoire de biométrie et biologie evolutive (LBBE)
      Villeurbanne, Rhône-Alpes, France
  • 2011-2012
    • French National Centre for Scientific Research
      • Laboratoire de Biométrie et Biologie Évolutive (LBBE)
      Lutetia Parisorum, Île-de-France, France
  • 2009
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2001-2008
    • Lyon Natecia Hospital
      Lyons, Rhône-Alpes, France
  • 2005
    • Université Pierre Mendès France - Grenoble 2
      Grenoble, Rhône-Alpes, France
    • Bellevue University
      Bellevue, Nebraska, United States
  • 2002
    • Centre Hospitalier Universitaire de Saint-Étienne
      • Department of Medicine and Therapeutics
      Saint-Étienne, Rhône-Alpes, France
    • Centre Hospitalier Universitaire de Grenoble
      Grenoble, Rhône-Alpes, France