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Coronary Artery Disease: HELP
Articles by Jean-Phillippe Collet
Based on 32 articles published since 2008
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Between 2008 and 2019, J-P Collet wrote the following 32 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. 2018

Valgimigli, Marco / Bueno, Héctor / Byrne, Robert A / Collet, Jean-Philippe / Costa, Francesco / Jeppsson, Anders / Jüni, Peter / Kastrati, Adnan / Kolh, Philippe / Mauri, Laura / Montalescot, Gilles / Neumann, Franz-Josef / Petricevic, Mate / Roffi, Marco / Steg, Philippe Gabriel / Windecker, Stephan / Zamorano, Jose Luis / Levine, Glenn N / Anonymous3740973. · ·Eur J Cardiothorac Surg · Pubmed #29045581.

ABSTRACT: -- No abstract --

2 Guideline [2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS.] 2017

Valgimigli, Marco / Bueno, Héctor / Byrne, Robert A / Collet, Jean-Philippe / Costa, Francesco / Jeppsson, Anders / Jüni, Peter / Kastrati, Adnan / Kolh, Philippe / Mauri, Laura / Montalescot, Gilles / Neumann, Franz-Josef / Peticevic, Mate / Roffi, Marco / Steg, Philippe Gabriel / Windecker, Stephan / Zamorano, Jose Luis. ·Cardiology, Inselspital, Bern. marco.valgimigli@insel.ch. ·Kardiol Pol · Pubmed #29251754.

ABSTRACT: -- No abstract --

3 Review Antiplatelet Agents for the Treatment and Prevention of Coronary Atherothrombosis. 2017

Patrono, Carlo / Morais, Joao / Baigent, Colin / Collet, Jean-Philippe / Fitzgerald, Desmond / Halvorsen, Sigrun / Rocca, Bianca / Siegbahn, Agneta / Storey, Robert F / Vilahur, Gemma. ·Department of Pharmacology, Catholic University School of Medicine, Rome, Italy. Electronic address: carlo.patrono@unicatt.it. · Division of Cardiology, Santo Andre's Hospital, Leiria, Portugal. · MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Sorbonne Université Paris 6, ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), INSERM UMRS 1166, Paris, France. · University of Limerick, Limerick, Ireland. · Department of Cardiology, Oslo University Hospital Ullevål, and University of Oslo, Oslo, Norway. · Department of Pharmacology, Catholic University School of Medicine, Rome, Italy. · Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden. · Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom. · Cardiovascular Science Institute-ICCC IIB-Sant Pau, CiberCV, Hospital de Sant Pau, Barcelona, Spain. ·J Am Coll Cardiol · Pubmed #28958334.

ABSTRACT: Antiplatelet drugs provide first-line antithrombotic therapy for the management of acute ischemic syndromes (both coronary and cerebrovascular) and for the prevention of their recurrence. Their role in the primary prevention of atherothrombosis remains controversial because of the uncertain balance of the potential benefits and risks when combined with other preventive strategies. The aim of this consensus document is to review the evidence for the efficacy and safety of antiplatelet drugs, and to provide practicing cardiologists with an updated instrument to guide their choice of the most appropriate antiplatelet strategy for the individual patient presenting with different clinical manifestations of coronary atherothrombosis, in light of comorbidities and/or interventional procedures.

4 Review Oral anticoagulants in coronary heart disease (Section IV). Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease. 2016

De Caterina, Raffaele / Husted, Steen / Wallentin, Lars / Andreotti, Felicita / Arnesen, Harald / Bachmann, Fedor / Baigent, Colin / Collet, Jean-Philippe / Halvorsen, Sigrun / Huber, Kurt / Jespersen, Jørgen / Kristensen, Steen Dalby / Lip, Gregory Y H / Morais, João / Rasmussen, Lars Hvilsted / Ricci, Fabrizio / Sibbing, Dirk / Siegbahn, Agneta / Storey, Robert F / Ten Berg, Jurriën / Verheugt, Freek W A / Weitz, Jeffrey I. ·Raffaele De Caterina, MD, PhD, Institute of Cardiology, "G. d'Annunzio" University - Chieti, Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy, E-mail: rdecater@unich.it. ·Thromb Haemost · Pubmed #26952877.

ABSTRACT: Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.

5 Review Dual antiplatelet therapy: optimal timing, management, and duration. 2015

Sabouret, Pierre / Rushton-Smith, Sophie K / Kerneis, Mathieu / Silvain, Johanne / Collet, Jean-Philippe / Montalescot, Gilles. ·Institut du Cœur, Pitié-Salpêtrière Hospital (AP-HP), Pierre and Marie Curie University, 47-83, boulevard de l'Hôpital, Paris 75013, France, ACTION Group, www.action-coeur.org. · Thrombosis Research Institute, London, UK. · Institut du Cœur, Pitié-Salpêtrière Hospital (AP-HP), Pierre and Marie Curie University, 47-83, boulevard de l'Hôpital, Paris 75013, France, ACTION Group, www.action-coeur.org gilles.montalescot@psl.aphp.fr. ·Eur Heart J Cardiovasc Pharmacother · Pubmed #27533996.

ABSTRACT: Platelet activation and aggregability play a key role in the genesis of arterial thrombus secondary to plaque rupture. For coronary patients, inhibition of platelet function is crucial to decrease the rate of major adverse cardiac events but may expose them to excess bleeding risk. Switching P2Y12 inhibitors is common, yet the clinical consequences are unknown. The aim of this review is to provide an overview of the evidence from randomized, clinical trials and epidemiological studies, with a focus on the optimal duration of dual antiplatelet therapy (DAPT) and appropriate agent and dose selection. The report discusses the latest evidence regarding switching therapies during DAPT, the potential benefits of a personalized strategy, management of the preoperative period, and other clinical perspectives in this complex and rapidly changing field. Ongoing trials will be useful to answer to some important unresolved questions.

6 Review Coronary revascularization in the diabetic patient. 2014

Silvain, Johanne / Vignalou, Jean-Baptiste / Barthélémy, Olivier / Kerneis, Mathieu / Collet, Jean-Philippe / Montalescot, Gilles. ·From the ACTION Coeur Research Group, Institut de Cardiologie, Pitié-Salpêtrière Hospital (APHP), Sorbonne Universités, (UPMC), INSERM, UMRS 1166, Paris, France. · From the ACTION Coeur Research Group, Institut de Cardiologie, Pitié-Salpêtrière Hospital (APHP), Sorbonne Universités, (UPMC), INSERM, UMRS 1166, Paris, France. gilles.montalescot@psl.aphp.fr. ·Circulation · Pubmed #25199665.

ABSTRACT: -- No abstract --

7 Review Open issues in transcatheter aortic valve implantation. Part 1: patient selection and treatment strategy for transcatheter aortic valve implantation. 2014

Bax, Jeroen J / Delgado, Victoria / Bapat, Vinayak / Baumgartner, Helmut / Collet, Jean P / Erbel, Raimund / Hamm, Christian / Kappetein, Arie P / Leipsic, Jonathon / Leon, Martin B / MacCarthy, Philip / Piazza, Nicolo / Pibarot, Philippe / Roberts, William C / Rodés-Cabau, Josep / Serruys, Patrick W / Thomas, Martyn / Vahanian, Alec / Webb, John / Zamorano, Jose Luis / Windecker, Stephan. ·Department of Cardiology, Leiden University Medical Center, Albinusdreef 2 2300 RC, Leiden, The Netherlands j.j.bax@lumc.nl. · Department of Cardiology, Leiden University Medical Center, Albinusdreef 2 2300 RC, Leiden, The Netherlands. · Department of Cardiology and Cardiothoracic Surgery, St Thomas' Hospital, London, UK. · Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany. · Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Department of Cardiology, West-German Heart Center Essen, University Duisburg Essen, Essen, Germany. · Department of Cardiology, Kerckhoff-Klinik, Bad Nauheim, Germany. · Erasmus Medical Center, Rotterdam, The Netherlands. · St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada. · Columbia University Medical Center, Center for Interventional Vascular Therapy, New York Presbyterian Hospital, New York, USA. · Cardiovascular Department, King's College Hospital, London, UK. · Interventional Cardiology, McGill University Health Center, Montreal, Canada Cardiovascular Surgery, German Heart Center Munich, Bavaria, Germany. · Quebec Heart and Lung Institute, Québec, Canada. · Baylor Heart and Vascular Institute and the Departments of Internal Medicine (Division of Cardiology) and Pathology, Baylor University Medical Center, Dallas, TX, USA. · Department of Cardiology, Laval University, Quebec, Canada. · Bichat Hospital, University Paris VII, Paris, France. · Cardiac Imaging Department, University Hospital Ramon y Cajal, Madrid, Spain. · Department of Cardiology, Bern University Hospital, Bern, Switzerland. ·Eur Heart J · Pubmed #25062952.

ABSTRACT: An exponential increase in the use of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis has been witnessed over the recent years. The current article reviews different areas of uncertainty related to patient selection. The use and limitations of risk scores are addressed, followed by an extensive discussion on the value of three-dimensional imaging for prosthesis sizing and the assessment of complex valve anatomy such as degenerated bicuspid valves. The uncertainty about valvular stenosis severity in patients with a mismatch between the transvalvular gradient and the aortic valve area, and how integrated use of echocardiography and computed tomographic imaging may help, is also addressed. Finally, patients referred for TAVI may have concomitant mitral regurgitation and/or coronary artery disease and the management of these patients is discussed.

8 Review Association of clopidogrel pretreatment with mortality, cardiovascular events, and major bleeding among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. 2012

Bellemain-Appaix, Anne / O'Connor, Stephen A / Silvain, Johanne / Cucherat, Michel / Beygui, Farzin / Barthélémy, Olivier / Collet, Jean-Philippe / Jacq, Laurent / Bernasconi, François / Montalescot, Gilles / Anonymous2460746. ·Service de Cardiologie-La FontonneHospital, Antibes, France. ·JAMA · Pubmed #23287889.

ABSTRACT: CONTEXT: Clopidogrel pretreatment is recommended for patients with acute coronary syndromes (ACS) and stable coronary artery disease who are scheduled for percutaneous coronary intervention (PCI), but whether using clopidogrel as a pretreatment for PCI is associated with positive clinical outcomes has not been established. OBJECTIVE: To evaluate the association of clopidogrel pretreatment vs no treatment with mortality and major bleeding after PCI. DATA SOURCES: MEDLINE, EMBASE, Cochrane Controlled Trials Register databases, and reference lists of qualifying articles. STUDY SELECTION Studies reporting clinical data on mortality and major bleeding were included. Of the 392 titles identified, 15 articles published between August 2001 and September 2012 met the inclusion criteria: 6 randomized controlled trials (RCTs), 2 observational analyses of RCTs, and 7 observational studies. DATA EXTRACTION: Quality of studies was assessed with the Ottawa Scale and the Jadad Score as appropriate. Results were independently extracted by 2 reviewers. A random-effect model was applied. Pretreatment was defined as the administration of clopidogrel before PCI or catheterization. The main analysis was performed on RCTs and confirmed by observational analyses and observational studies. Prespecified subgroups--clinical presentation and clopidogrel loading dose--were analyzed. The primary efficacy and safety end points were all-cause mortality and major bleeding. Secondary end points included major cardiac events. RESULTS: Of the 37 814 patients included in the meta-analysis, 8608 patients had participated in RCTs; 10,945, in observational analyses of RCTs; and 18,261, in observational studies. Analysis of RCTs showed that clopidogrel pretreatment was not associated with a reduction of death (absolute risk, 1.54% vs 1.97%; OR, 0.80; 95% CI, 0.57-1.11; P = .17) but was associated with a lower risk of major cardiac events (9.83% vs 12.35%; OR, 0 .77; 95% CI, 0.66-0.89; P < .001). There was no significant association between pretreatment and major bleeding overall (3 .57% vs 3.08%; OR, 1.18; 95% CI, 0.93-1.50; P = .18). Analyses from observational analyses of RCTs and observational studies were consistent for all results. CONCLUSIONS: Among patients scheduled for PCI, clopidogrel pretreatment was not associated with a lower risk of mortality but was associated with a lower risk of major coronary events.

9 Review Antiplatelet agents for the treatment and prevention of atherothrombosis. 2011

Patrono, Carlo / Andreotti, Felicita / Arnesen, Harald / Badimon, Lina / Baigent, Colin / Collet, Jean-Philippe / De Caterina, Raffaele / Gulba, Dietrich / Huber, Kurt / Husted, Steen / Kristensen, Steen Dalby / Morais, João / Neumann, Franz-Josef / Rasmussen, Lars Hvilsted / Siegbahn, Agneta / Steg, Philippe-Gabriel / Storey, Robert F / Van de Werf, Frans / Verheugt, Freek. ·Department of Pharmacology, Catholic University School of Medicine, Rome, Italy. carlo.patrono@rm.unicatt.it ·Eur Heart J · Pubmed #22019823.

ABSTRACT: The clinical pharmacology of antiplatelet drugs has been reviewed previously by the European Society of Cardiology (ESC) Task force and by the 8th American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. Moreover, information on the efficacy and safety of antiplatelet drugs in the treatment and prevention of atherothrombosis is provided by collaborative meta-analyses of 287 secondary prevention trials and 6 primary prevention trials. The present document intends to provide practicing physicians with an updated instrument to guide their choice of the most suitable antiplatelet strategy for the individual patient at risk, or with different clinical manifestations, of atherothrombosis.

10 Article Systematic detection of polyvascular disease combined with aggressive secondary prevention in patients presenting with severe coronary artery disease: The randomized AMERICA Study. 2018

Collet, Jean-Philippe / Cayla, Guillaume / Ennezat, Pierre-Vladimir / Leclercq, Florence / Cuisset, Thomas / Elhadad, Simon / Henry, Patrick / Belle, Loic / Cohen, Ariel / Silvain, Johanne / Barthelemy, Olivier / Beygui, Farzin / Diallo, Abdourahmane / Vicaut, Eric / Montalescot, Gilles / Anonymous6390935. ·Sorbonne Université Paris 6, ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), INSERM UMRS, 1166 Paris, France. Electronic address: jean-philippe.collet@psl.aphp.fr. · ACTION Study Group, Cardiologie, CHU Carémeau, Université de Montpellier, Nîmes, France. · Cardiologie, Pôle Thorax et Vaisseaux, CHU La Tronche, Grenoble, France. · Cardiologie, Hôpital Arnaud de Villeneuve-CHU Montpellier, France. · Department of Cardiology, CHU Timone and Aix-Marseille Univ, INSERM UMR1062, INRA UMR1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, F-13385 Marseille, France. · Cardiologie, CH de Lagny-Marne la Vallée, Jossigny, France. · Cardiologie, CHU Lariboisière (APHP), Paris, France. · Cardiologie, Centre Hospitalier d'Annecy, France. · Cardiologie, CHU Saint-Antoine (APHP), Paris, France. · Sorbonne Université Paris 6, ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), INSERM UMRS, 1166 Paris, France. · Cardiologie, Hôpital de la Côte de Nacre, Caen, France. · ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP), France and Université Denis Diderot, Paris, France. ·Int J Cardiol · Pubmed #29407124.

ABSTRACT: BACKGROUND: The prevalence and associated-risk of asymptomatic multisite artery disease (MSAD) in high risk coronary patients are unknown. Whether systematic identification and aggressive management of asymptomatic MSAD is clinically relevant in high risk coronary patients has not been evaluated. METHODS: We randomly assigned 521 high risk coronary patients defined by the presence of three-vessel coronary disease (n=304) or recent acute coronary syndrome beyond the age of 75years (n=215) to either a strategy of systematic detection of asymptomatic MSAD combined with an aggressive secondary prevention (n=263) or to a more conventional strategy based on treatment of coronary artery disease only with standard of care (n=258). The primary end point was the time to first occurrence of death, any organ failure or ischemic event leading to re-hospitalization through two years of follow-up. RESULTS: The pro-active strategy identified asymptomatic MSAD in 21.7% of patients with few revascularizations (3.6%); the pro-active pharmacological secondary prevention was obtained in >85% of patients and life-style changes in <60% of patients. At 2-year follow-up, the primary end point occurred in 44.9% of patients in the pro-active group and 43.0% of patients in the conventional group (HR 1.03; 95% confidence interval [CI], 0.80 to 1.34]. The rate of major bleeding did not differ significantly between groups (4.6% vs 5.0%; HR, 0.97; 95% CI, 0.40 to 1.91). CONCLUSION: In high risk coronary patients, there is no apparent benefit of a systematic detection of asymptomatic extra-coronary atherothrombotic disease and intensified treatment over a 2-year follow-up period. (Funded by the Academic Allies in Cardiovascular Trials Initiatives and Organized Networks and Institut de l'Athérothrombose; AMERICA ClinicalTrials.gov number, NCT00445835).

11 Article Outcome after revascularisation of acute myocardial infarction with cardiogenic shock on extracorporeal life support. 2018

Overtchouk, Pavel / Pascal, Julien / Lebreton, Guillaume / Hulot, Jean-Sebastien / Luyt, Charles-Edouard / Combes, Alain / Kerneis, Mathieu / Silvain, Johanne / Barthelemy, Olvier / Leprince, Pascal / Brechot, Nicolas / Montalescot, Gilles / Collet, Jean-Philippe. ·Sorbonne Université, ACTION Study Group, INSERM UMR_S 1166, Institut de Cardiologie, Département de Cardiologie, Pitié-Salpêtrière Hospital (AP-HP), Paris, France. ·EuroIntervention · Pubmed #29400656.

ABSTRACT: AIMS: The aim of the study was to identify independent correlates of survival in patients undergoing PCI for refractory cardiogenic shock due to myocardial infarction (RCS-MI) with the need for extracorporeal life support (ECLS). METHODS AND RESULTS: This observational single tertiary centre study enrolled 106 consecutive patients (52.7±10.4 years) with ECLS placed before or after the PCI. Half of the patients had triple vessel disease and PCI was attempted whenever possible (74.5%). The 30-day mortality rate was 63.2%. Left main culprit vessel disease (19% of patients) (adj. HR [95% CI]: 2.31 [1.27-4.18], p=0.006) and sepsis-related organ failure assessment ≥13 (adj. HR 2.17 [1.25-3.75], p=0.005) were independently associated with 30-day mortality. The use of intra-aortic balloon pump (IABP) combined with ECLS was an independent protective factor (adj. HR 0.48 [0.28-0.80], p=0.006). Neither complete (p=0.66) nor successful (p=0.69) myocardial revascularisation was associated with 30-day survival. CONCLUSIONS: RCS in MI patients often reveals a severe multivessel coronary artery disease with no impact of early percutaneous coronary revascularisation on clinical outcome. The survival advantage of IABP when combined with ECLS further suggests that achieving an early effective haemodynamic support should be the major goal in this young patient population.

12 Article Impact of coronary artery disease in patients undergoing transcatheter aortic valve replacement: Insights from the FRANCE-2 registry. 2017

Puymirat, Etienne / Didier, Romain / Eltchaninoff, Hélène / Lung, Bernard / Collet, Jean-Philippe / Himbert, Dominique / Durand, Eric / Leguerrier, Alain / Leprince, Pascal / Fajadet, Jean / Teiger, Emmanuel / Chevreul, Karine / Lièvre, Michel / Tchetché, Didier / Leclercq, Florence / Chassaing, Stéphan / Le Breton, Hervé / Donzeau-Gouge, Patrick / Lefèvre, Thierry / Carrié, Didier / Gillard, Martine / Blanchard, Didier. ·Department of Cardiology, European Hospital of Georges Pompidou, Public Assistance Hospitals of Paris, Paris Descartes University, Paris, France. · Department of Cardiology, Brest University Hospital, Brest, France. · Department of Cardiology, Rouen University Hospital, Rouen, France. · Department of Cardiology, Bichat University Hospital, Paris, France. · Department of Cardiology, Pitié Salpetrière University Hospital, Paris, France. · Department of Cardiology and Surgery, Rennes University Hospital, Rennes, France. · Department of Surgery, Pitié Salpetrière University Hospital, Paris, France. · Department of Cardiology, Clinique Pasteur, Toulouse, France. · Department of URC-ECO and Cardiology, Creteil University Hospital, Paris, France. · Public Assistance Hospitals of Paris, Hotel Dieu Hospital, Clinical Research Unit, Paris, France. · UMR and Department of Cardiology, Lyon University Hospital, Lyon, France. · Department of Cardiology, Montpellier University Hospital, Montpellier, France. · Department of Cardiology, Clinique Saint-Gatien, Tours, France. · Department of Cardiology, Rennes University Hospital, Rennes, France. · Department of Cardiology and Surgery, I Cardiovascular Institute Paris Sud, Private Hospital Jacques Cartier, Massy, France. · Department of Cardiology, CHU Toulouse Rangueil, University Paul Sabatier, Toulouse, France. ·Clin Cardiol · Pubmed #29247516.

ABSTRACT: BACKGROUND: Coronary artery disease (CAD) is common in patients undergoing transcatheter aortic valve replacement (TAVR). However, the impact of CAD distribution before TAVR on short- and long-term prognosis remains unclear. HYPOTHESIS: We hypothesized that the long-term clinical impact differs according to CAD distribution in patients undergoing TAVR using the FRench Aortic National CoreValve and Edwards (FRANCE-2) registry. METHODS: FRANCE-2 is a national French registry including all consecutive TAVR performed between 2010 and 2012 in 34 centers. Three-year mortality was assessed in relation to CAD status. CAD was defined as at least 1 coronary stenosis >50%. RESULTS: A total of 4201 patients were enrolled in the registry. For the present analysis, we excluded patients with a history of coronary artery bypass. CAD was reported in 1252 patients (30%). Half of the patients presented with coronary multivessel disease. CAD extent was associated with an increase in cardiovascular risk profile and in logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (from 19.3% ± 12.8% to 21.9% ± 13.5%, P < 0.001). Mortality at 30 days and 3 years was 9% and 44%, respectively, in the overall population. In multivariate analyses, neither the presence nor the extent of CAD was associated with mortality at 3 years (presence of CAD, hazard ratio [HR]: 0.90; 95% confidence interval [CI]: 0.78-1.07). A significant lesion of the left anterior descending (LAD) was associated with higher 3-year mortality (HR: 1.42; 95% CI: 1.10-1.87). CONCLUSIONS: CAD is not associated with decreased short- and long-term survival in patients undergoing TAVR. The potential deleterious effect of LAD disease on long-term survival and the need for revascularization before or at the time of TAVR should be validated in a randomized control trial.

13 Article Exome sequencing of extreme clopidogrel response phenotypes identifies B4GALT2 as a determinant of on-treatment platelet reactivity. 2016

Scott, S A / Collet, J-P / Baber, U / Yang, Y / Peter, I / Linderman, M / Sload, J / Qiao, W / Kini, A S / Sharma, S K / Desnick, R J / Fuster, V / Hajjar, R J / Montalescot, G / Hulot, J-S. ·Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Sorbonne Universités, UPMC Univ Paris 06, Faculty of Medicine, UMRS_1166 ICAN, Institute of Cardiometabolism and Nutrition, AP-HP, Pitié-Salpêtrière Hospital, Institute of Cardiology, Paris, France. · Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ·Clin Pharmacol Ther · Pubmed #27213804.

ABSTRACT: Interindividual variability in platelet aggregation is common among patients treated with clopidogrel and both high on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, patients with coronary artery disease (CAD) with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n = 636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRUs; P = 0.0077) and residual platelet aggregation (P = 0.0008) compared with noncarriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (P = 0.0298) and replication (n = 160; PRU: P = 0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion.

14 Article Clinical Outcome of First- vs Second-Generation DES According to DAPT Duration: Results of ARCTIC-Generation. 2016

Collet, Jean-Philippe / Silvain, Johanne / Kerneis, Mathieu / Cuisset, Thomas / Meneveau, Nicolas / Boueri, Ziad / Barthélémy, Olivier / Rangé, Grégoire / Cayla, Guillaume / Belle, Eric Van / Elhadad, Simon / Carrié, Didier / Caussin, Christophe / Rousseau, Hélène / Aubry, Pierre / Monségu, Jacques / Sabouret, Pierre / O'Connor, Stephen A / Abtan, Jérémie / Saint-Etienne, Christophe / Beygui, Farzin / Vicaut, Eric / Montalescot, Gilles / Anonymous3920858. ·Univ Paris 06 (UPMC), ACTION Study Group, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (APHP), Paris, France. · Department of Cardiology, CHU La Timone, Marseille, France. · Department of Cardiology, CHU Jean Minjoz, Besançon, France. · Department of Cardiology, CH de Bastia, France. · Department of Cardiology, Les Hôpitaux de Chartres, Le Coudray, France. · ACTION Study Group, Department of Cardiology, CHU Carémeau, Nîmes, France. · Department of Cardiology, Lille University Hospital, Lille, France. · Department of Cardiology, CH de Lagny-Marne la Vallée, Lagny-sur-Marne, France. · Department of Cardiology, CHU Rangueil, Toulouse, France. · Department of Cardiology, Institut Mutualiste Montsouris, Paris, France. · ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP), Paris, France. · Université Denis Diderot, Paris, France. · Department of Cardiology, Centre Hospitalier Bichat (APHP), Paris, France. · Department of cardiology, Groupe Hospitalier Mutualiste, Grenoble, France. · Department of Cardiology, CHU Trousseau, Tours, France. · ACTION Study Group, CHU Côte de Nacre, Caen, France. ·Clin Cardiol · Pubmed #26880570.

ABSTRACT: There is an apparent benefit with extension of dual antiplatelet therapy (DAPT) beyond 1 year after implantation of drug-eluting stents (DES). Assessment by a Double Randomization of a Conventional Antiplatelet Strategy vs a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation, and of Treatment Interruption vs Continuation One Year After Stenting (ARCTIC)-Generation assessed whether there is a difference of outcome between first- vs second-generation DES and if there is an interaction with DAPT duration in the ARCTIC-Interruption study. ARCTIC-Interruption randomly allocated 1259 patients 1 year after stent implantation to a strategy of interruption of DAPT (n = 624), in which aspirin antiplatelet treatment only was maintained, or DAPT continuation (n = 635) for 6 to 18 additional months. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization. A total of 520 and 722 patients received a first- and a second-generation DES, respectively. After a median follow-up of 17 months (interquartile range, 15-18 months) after randomization, the primary endpoint occurred in 32 (6.2%) and 19 (2.6%) patients with first- and second-generation DES, respectively (hazard ratio: 2.31, 95% confidence interval: 1.31-4.07, P = 0.004). This was observed irrespective of the strategy of interruption or continuation of DAPT and timing of study recruitment. Major bleeding events occurred in 4 (0.8%) and 3 patients (0.4%) with first- and second-generation DES, respectively (hazard ratio: 1.79, 95% confidence interval: 0.40-8.02, P = 0.44). Results did not change after multiple adjustments for potential confounding variables. ARCTIC-Generation showed worse clinical outcome with first- vs second-generation DES, a difference that appeared to persist even with prolonged DAPT.

15 Article Impact of renal failure on all-cause mortality and other outcomes in patients treated by percutaneous coronary intervention. 2015

Loncar, Goran / Barthelemy, Olivier / Berman, Emmanuel / Kerneis, Mathieu / Petroni, Thibault / Payot, Laurent / Choussat, Remi / Silvain, Johanne / Collet, Jean-Philippe / Helft, Gérard / Montalescot, Gilles / Le Feuvre, Claude. ·Institut de cardiologie, université Paris 6, CHU Pitié-Salpêtrière, AP-HP, Paris, France; Cardiology Department, Clinical Hospital Zvezdara, Belgrade, Serbia. · Institut de cardiologie, université Paris 6, CHU Pitié-Salpêtrière, AP-HP, Paris, France. Electronic address: olivier.barthelemy@psl.aphp.fr. · Institut de cardiologie, université Paris 6, CHU Pitié-Salpêtrière, AP-HP, Paris, France. ·Arch Cardiovasc Dis · Pubmed #26184868.

ABSTRACT: BACKGROUND: Patients with renal failure (RF) have been systematically excluded from clinical trials; consequently their outcomes have not been well studied in the setting of percutaneous coronary intervention (PCI). AIMS: To compare cardiovascular outcomes after contemporary PCI in patients with versus without RF, according to clinical presentation (ST-segment elevation myocardial infarction [STEMI], acute coronary syndrome [ACS] or stable coronary artery disease [sCAD]). METHODS: Consecutive patients undergoing PCI with stent were prospectively included from 2007 to 2012. RF was defined as creatinine clearance<60mL/min. The primary endpoint was all-cause mortality; secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE: composite of cardiovascular death, myocardial infarction, stroke and target lesion revascularization [TLR]), TLR and Academic Research Consortium definite/probable stent thrombosis (ST) at 1 year. RESULTS: Among 5337 patients, 23% had PCI for STEMI, 34% for ACS and 43% for sCAD, while 27% had RF. RF patients had a higher unadjusted death rate than those with preserved renal function (nRF) in all PCI indication groups (STEMI, 41% vs. 7.5%; ACS, 19% vs. 6%; sCAD, 10% vs. 3%; P<0.0001 for all). The rate of MACCE was also higher in RF patients whatever the PCI indication (STEMI, 45% vs. 15%; ACS, 23% vs. 14%; sCAD, 14% vs. 9%; P<0.05 for all). Rates of TLR (5.5-7.4%) and ST (<2.5%) were similar (P>0.05 for both). sCAD-RF and STEMI-nRF patients had similar rates of mortality (P=0.209) and MACCE (P=0.658). RF was independently associated with mortality, with a doubled relative risk in STEMI versus ACS and sCAD groups (odds ratio 5.3, 95% confidence interval 3.627-7.821 vs. 2.1, 1.465-3.140 and 2.3, 1.507-3.469, respectively; P<0.0001). CONCLUSION: RF is a stronger independent predictor of death after PCI in STEMI than in ACS or sCAD patients. sCAD-RF and STEMI-nRF patients had similar prognoses.

16 Article Omeprazole, pantoprazole, and CYP2C19 effects on clopidogrel pharmacokinetic-pharmacodynamic relationships in stable coronary artery disease patients. 2015

Simon, Nicolas / Finzi, Jonathan / Cayla, Guillaume / Montalescot, Gilles / Collet, Jean-Philippe / Hulot, Jean-Sébastien. ·Aix-Marseille Université, INSERM, UMR912 (SESSTIM), 13003, Marseille, France, nicolas.simon@ap-hm.fr. ·Eur J Clin Pharmacol · Pubmed #26071277.

ABSTRACT: PURPOSE: Proton-pump Inhibitors use and CYP2C19 loss-of-function alleles are associated with reduced responsiveness to standard clopidogrel doses and increased cardiovascular events. METHODS: Post-myocardial infarction patients heterozygous (wild type [wt]/*2, n = 41) or homozygous (*2/*2, n = 7) for the CYP2C19*2 genetic variant were matched with patients not carrying the variant (wt/wt, n = 58). All patients were randomized to a 300- or 900-mg clopidogrel loading dose. A PK/PD model was defined using the variation of the P2Y12 reaction unit relative to baseline. RESULTS: Carriage of CYP2C19*2 allele and the use of omeprazole/esomeprazole were associated with the inter-individual variability in the active metabolite clearance. The relationship between inhibition of platelet aggregation (IPA, %) and the active metabolite AUC (h*μg/L) was described by a sigmoid function (Emax 56 ± 5%; EAUC50 15.9 ± 0.8 h*μg/L) with a gamma exponent (7.04 ± 2.26). CONCLUSION: This on/off shape explains that a small variation of exposure may have a clinical relevance.

17 Article Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. 2014

Collet, Jean-Philippe / Silvain, Johanne / Barthélémy, Olivier / Rangé, Grégoire / Cayla, Guillaume / Van Belle, Eric / Cuisset, Thomas / Elhadad, Simon / Schiele, François / Lhoest, Nicolas / Ohlmann, Patrick / Carrié, Didier / Rousseau, Hélène / Aubry, Pierre / Monségu, Jacques / Sabouret, Pierre / O'Connor, Stephen A / Abtan, Jérémie / Kerneis, Mathieu / Saint-Etienne, Christophe / Beygui, Farzin / Vicaut, Eric / Montalescot, Gilles / Anonymous6280800. ·ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France. · Les Hôpitaux de Chartres, Le Coudray, France. · ACTION Study Group, Cardiologie, CHU Carémeau, Nîmes, France. · CHRU de Lille, Lille, France. · Département de Cardiologie, CHU La Timone, Marseille, France. · Cardiologie, CH de Lagny-Marne-la-Vallée, Lagny-sur-Marne, France. · CHU Jean Minjoz, Besançon, France. · GH du Centre Alsace, France. · CHR Strasbourg, France. · CHU Rangueil, Toulouse, France. · CHRU de Lille, Lille, France; ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP), and Université Denis Diderot, Paris, France. · Centre Hospitalier Bichat (APHP), Paris, France. · Institut Mutualiste Montsouris, Paris, France. · CHU Trousseau, Tours, France. · ACTION study Group, CHU Caen, France. · ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP), and Université Denis Diderot, Paris, France. · ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP), Université Paris 6, INSERM, Paris, France. Electronic address: gilles.montalescot@psl.aphp.fr. ·Lancet · Pubmed #25037988.

ABSTRACT: BACKGROUND: Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial. METHODS: This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES). We recruited patients (aged 18 years or older) scheduled for planned DES implantation at 38 centres in France. After 1 year of follow-up, patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study (ARCTIC-Interruption). Using a computer-generated randomisation sequence (1:1; stratified by centre), we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained (interruption group) or a strategy of DAPT continuation for 6-18 months (continuation group). The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularisation, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00827411. FINDINGS: Between Jan 4, 2011, and March 3, 2012, 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption: 624 to the interruption group and 635 to the continuation group. After a median follow-up of 17 months (IQR 15-18), the primary endpoint occurred in 27 (4%) patients in the interruption group and 24 (4%) patients in the continuation group (hazard ratio [HR] 1·17 [95% CI 0·68-2·03]; p=0·58). STEEPLE major bleeding events occurred more often in the continuation group (seven [1%] patients) compared with the interruption group (one [<0·5%] patient; HR 0·15 [0·02-1·20]; p=0·073). Major or minor bleedings were also more common in the continuation group compared with the interruption group (12 [2%] patients vs three [1%] patients; HR 0·26 [0·07-0·91]; p=0·04). INTERPRETATION: Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment. FUNDING: Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.

18 Article Prasugrel but not high dose clopidogrel overcomes the lansoprazole neutralizing effect of P2Y12 inhibition: Results of the randomized DOSAPI study. 2014

Collet, Jean-Philippe / Hulot, Jean-Sébastien / Abtan, Jérémie / Anzaha, Ghalia / Kerneis, Mathieu / Silvain, Johanne / Cayla, Guillaume / O'Connor, Stephen A / Barthélémy, Olivier / Beygui, Farzin / Galier, Sophie / Brugier, Delphine / Stanek, Eric J / Charland, Scott L / Gallois, Vanessa / Montalescot, Gilles / Anonymous680800. ·ACTION Study Group, Hôpital Pitié-Salpêtrière (APHP), Institut de Cardiologie, INSERM, UMR_S 1166, Pitié-Salpêtrière Hospital (AP-HP), Université Pierre et Marie Curie (UPMC Paris 6), 75013, Paris, France. ·Eur J Clin Pharmacol · Pubmed #25012577.

ABSTRACT: AIMS: The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150 mg) would be less effective than switching to prasugrel 10 mg maintenance dose (MD) to overcome this negative interaction. METHOD AND RESULTS: In a randomized study with a factorial design, 82 stable coronary artery disease patients treated with 75 mg clopidogrel MD and aspirin were assigned to receive in a double blind fashion lansoprazole (30 mg/day) or placebo and to receive in an open fashion 150 mg clopidogrel MD or 10 mg prasugrel MD. The primary endpoint was the relative change in residual platelet reactivity over the 14-day study period [(RPA14day-RPAbaseline)/RPAbaseline]. The effect of doubling the clopidogrel MD on relative change in RPA was neutralized by lansoprazole (-53.6±48.4% versus +0.8±53.7% without and with lansoprazole, respectively, p = 0.02) whereas 10 mg of prasugrel MD dramatically reduced RPA irrespective of lansoprazole co-administration (-81.8 %±24.8% vs. -72.9%±32.9% without and with lansoprazole, respectively, p = NS). Lansoprazole exposure was the only parameter with a significant interaction with RPA among subgroups. CONCLUSION: The higher platelet inhibitory effect obtained by doubling the clopidogrel MD was totally neutralized by the co-administration of lansoprazole. This drug interaction was not observed with prasugrel 10 mg.

19 Article Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis. 2014

Windecker, Stephan / Stortecky, Stefan / Stefanini, Giulio G / da Costa, Bruno R / Rutjes, Anne Wilhelmina / Di Nisio, Marcello / Silletta, Maria G / Maione, Ausilia / Alfonso, Fernando / Clemmensen, Peter M / Collet, Jean-Philippe / Cremer, Jochen / Falk, Volkmar / Filippatos, Gerasimos / Hamm, Christian / Head, Stuart / Kappetein, Arie Pieter / Kastrati, Adnan / Knuuti, Juhani / Landmesser, Ulf / Laufer, Günther / Neumann, Franz-Joseph / Richter, Dimitri / Schauerte, Patrick / Sousa Uva, Miguel / Taggart, David P / Torracca, Lucia / Valgimigli, Marco / Wijns, William / Witkowski, Adam / Kolh, Philippe / Jüni, Peter. · ·BMJ · Pubmed #24958153.

ABSTRACT: OBJECTIVE: To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. DESIGN: Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. DATA SOURCES: Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. MAIN OUTCOME MEASURE: All cause mortality. RESULTS: 100 trials in 93,553 patients with 262,090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment. CONCLUSION: Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment.

20 Article High on-treatment platelet reactivity as a risk factor for secondary prevention after coronary stent revascularization: A landmark analysis of the ARCTIC study. 2014

Montalescot, Gilles / Rangé, Grégoire / Silvain, Johanne / Bonnet, Jean-Louis / Boueri, Ziad / Barthélémy, Olivier / Cayla, Guillaume / Belle, Loic / Van Belle, Eric / Cuisset, Thomas / Elhadad, Simon / Pouillot, Christophe / Henry, Patrick / Motreff, Pascal / Carrié, Didier / Rousseau, Hélène / Aubry, Pierre / Monségu, Jacques / Sabouret, Pierre / O'Connor, Stephen A / Abtan, Jérémie / Kerneis, Mathieu / Saint-Etienne, Christophe / Beygui, Farzin / Vicaut, Eric / Collet, Jean-Philippe / Anonymous6300790. ·From the ACTION Study Group, Institut de Cardiologie (AP-HP), INSERM UMRS 1166, Université Paris 6, Paris, France (G.M., J.S., O.B., P.S., S.A.O., M.K., J.-P.C.) · Hôpital Louis Pasteur, Le Coudray, France (G.R.) · Hôpital de la Timone, Marseille, France (J.-L.B., T.C.) · CH de Bastia, Bastia, France (Z.B.) · CHU Carémeau, Nîmes, France (G.C.) · CH de la Région Annecienne, Annecy, France (L.B.) · Hôpital Cardiologique, Lille, France (E.V.B.) · CH de Lagny, Marne-la-Vallée, France (S.E.) · Clinique Sainte-Clothilde, La Réunion, France (C.P.) · Hôpital Lariboisière, Paris, France (P.H.) · CHU Clermont-Ferrand, Clermont-Ferrand, France (P.M.) · Hôpital de Rangueil, Toulouse, France (D.C.) · Unite de Recherche Clinique, Hôpital Lariboisière, ACTION Study Group, Paris, France (H.R., E.V.) · Hôpital Bichat, Paris, France (P.A.) · HIA du Val-du-Grâce, Paris, France (J.M.) · Hôpital Bichat, ACTION Study Group, Paris, France (J.A.) · Hôpital Trousseau, Chambray-lès-Tours, ACTION Study Group, Paris, France (C.S.-E.) · and CHU Côte de Nacre, Caen, ACTION Study Group, Caen, France (F.B.). ·Circulation · Pubmed #24718568.

ABSTRACT: BACKGROUND: Individualizing antiplatelet therapy after platelet function testing did not improve outcome after coronary stenting in the Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting (ARCTIC) study. Whether results are different during the phase of secondary prevention starting after hospital discharge, when periprocedural events have been excluded, is unknown. METHODS AND RESULTS: In ARCTIC, 2440 patients were randomized before coronary stenting to a strategy of platelet function monitoring (VerifyNow P2Y12/aspirin point-of-care assay) with drug adjustment in suboptimal responders to antiplatelet therapy or to a conventional strategy without monitoring and without drug or dose changes. We performed a landmark analysis starting at the time of hospital discharge evaluating the primary end point of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization through 1 year. After discharge, the primary end point occurred in 8.6% of patients in the monitoring arm and 7.9% in the conventional arm (hazard ratio, 1.105; 95% confidence interval, 0.835-1.461; P=0.48). Stent thrombosis or urgent revascularization occurred in 4.4% and 4.5% in the monitoring and conventional arms, respectively (P=0.99). There was no difference for any of the other ischemic end points. Major bleeding event rates were 1.8% in the monitoring arm and 2.8% in the conventional arm (P=0.11), whereas major or minor bleeding event rates were 2.3% and 3.4%, respectively (P=0.10). CONCLUSIONS: Detection of platelet hyper-reactivity by platelet function testing in patients undergoing coronary stenting with further therapeutic adjustment does not reduce ischemic recurrences after intervention. On-treatment platelet hyperreactivity cannot be considered as a risk factor requiring intervention for secondary prevention after percutaneous coronary revascularization. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00827411.

21 Article Impact of red blood cell transfusion on platelet aggregation and inflammatory response in anemic coronary and noncoronary patients: the TRANSFUSION-2 study (impact of transfusion of red blood cell on platelet activation and aggregation studied with flow cytometry use and light transmission aggregometry). 2014

Silvain, Johanne / Abtan, Jérémie / Kerneis, Mathieu / Martin, Réjane / Finzi, Jonathan / Vignalou, Jean-Baptiste / Barthélémy, Olivier / O'Connor, Stephen A / Luyt, Charles-Edouard / Brechot, Nicolas / Mercadier, Anne / Brugier, Delphine / Galier, Sophie / Collet, Jean-Philippe / Chastre, Jean / Montalescot, Gilles. ·Institut de Cardiologie, Institut National de la Santé et de la Recherche Médicale CMR937, Allies in Cardiovascular Trials Initiatives and Organized Networks Group, Pitié-Salpêtrière Hospital (Assistance Publique - Hôpitaux de Paris), Université Pierre et Marie Curie, Paris, France. · Service de Réanimation Médicale, Pitié-Salpêtrière Hospital (Assistance Publique - Hôpitaux de Paris), Université Pierre et Marie Curie, Paris, France. · Etablissement Français du Sang Ile-de-France, CR4, Pitié-Salpêtrière Hospital (Assistance Publique - Hôpitaux de Paris), Paris, France. · Institut de Cardiologie, Institut National de la Santé et de la Recherche Médicale CMR937, Allies in Cardiovascular Trials Initiatives and Organized Networks Group, Pitié-Salpêtrière Hospital (Assistance Publique - Hôpitaux de Paris), Université Pierre et Marie Curie, Paris, France. Electronic address: gilles.montalescot@psl.aphp.fr. ·J Am Coll Cardiol · Pubmed #24361322.

ABSTRACT: OBJECTIVES: This study sought to determine whether red blood cell (RBC) transfusion increases in vivo platelet aggregation and inflammation in coronary and noncoronary patients. BACKGROUND: RBC transfusion increases in vitro platelet activation and aggregation in healthy volunteers, providing a possible explanation for the increase in recurrent ischemic events and mortality reported after RBC transfusion in patients with acute coronary syndromes (ACS). METHODS: Platelet reactivity was measured before and after RBC transfusion in 61 patients (33 with ACS patients and 28 without ACS). Relative changes between baseline and post-transfusion measurements of maximal and residual platelet aggregation were considered with different agonists as well as changes in vasodilator-stimulated phosphoprotein platelet reactivity index and P-selectin expression. Inflammatory and thrombotic biomarkers were also measured before and after transfusion. RESULTS: After RBC transfusion, platelet reactivity was increased when measured using adenosine diphosphate-induced light transmission aggregometry (11.6% relative increase in maximal platelet aggregation, p = 0.004; 10.8% increase in residual platelet aggregation, p = 0.005) and vasodilator-stimulated phosphoprotein platelet reactivity index (20.7% relative increase, p = 0.002), and there was a nonsignificant trend toward an increase in P-selectin expression. Similar results were found with the nonspecific agonist thrombin receptor-activated peptide (relative increases of 11.7% for maximal platelet aggregation, p = 0.04, and 12.7% for residual platelet aggregation, p = 0.02) but not with collagen or arachidonic acid agonists. There were no significant differences in inflammatory and thrombotic biomarkers before and after transfusion. CONCLUSIONS: After RBC transfusion, there is an increase in platelet reactivity, especially with tests measuring the adenosine diphosphate-P2Y12 receptor pathway, without significant variations in inflammatory or thrombotic biomarkers. This in vivo effect may account for the excess of ischemic events observed in the context of patients with ACS treated using percutaneous coronary intervention and P2Y12 inhibitors.

22 Article Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure. 2012

Ivanes, Fabrice / Susen, Sophie / Mouquet, Frédéric / Pigny, Pascal / Cuilleret, François / Sautière, Karine / Collet, Jean-Philippe / Beygui, Farzin / Hennache, Bernadette / Ennezat, Pierre Vladimir / Juthier, Françis / Richard, Florence / Dallongeville, Jean / Hillaert, Marieke A / Doevendans, Pieter A / Jude, Brigitte / Bertrand, Michel / Montalescot, Gilles / Van Belle, Eric. ·Department of Cardiology, University Hospital, Lille, France. ·Eur Heart J · Pubmed #21719456.

ABSTRACT: BACKGROUND: Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. METHODS AND RESULTS: In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). CONCLUSION: Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.

23 Article One-year clinical outcomes in patients with chronic renal failure treated by percutaneous coronary intervention with drug-eluting stent. 2011

Barthelemy, Olivier / Helft, Gérard / Silvain, Johanne / Bellemain-Appaix, Anne / Beygui, Farzin / Choussat, Rémi / Berman, Emmanuel / Collet, Jean-Philippe / Montalescot, Gilles / Metzger, Jean-Philippe / Le Feuvre, Claude. ·Centre hospitalier universitaire Pitié-Salpêtrière, AP-HP, institut de cardiologie, 47, boulevard de l'hôpital, 75013 Paris, France. ·Arch Cardiovasc Dis · Pubmed #22152512.

ABSTRACT: BACKGROUND: It is unknown whether the efficacy and safety of drug-eluting stents (DES) apply in patients with chronic renal failure (CRF). AIMS: To compare DES with bare metal stents (BMS) for percutaneous coronary intervention (PCI) in CRF patients. PATIENTS AND METHODS: Consecutive patients treated by PCI were allocated to four groups according to type of stent used (DES versus BMS) and creatinine clearance (CrCl). CRF was defined as CrCl less than 60 mL/minute. Cardiovascular death, major adverse cardiac events (MACE, defined as cardiovascular death, myocardial infarction, stroke and target lesion revascularization [TLR]), TLR and definite stent thrombosis (ST) were recorded at 1 year. RESULTS: We note that 1376 consecutive patients underwent PCI with stent within 18 months: 534 (39%) and 492 (36%) patients without CRF and 224 (16%) and 126 (9%) patients with CRF were treated with BMS and DES, respectively. In the entire cohort, patients treated with DES had a higher restenosis risk profile. BMS were predominantly (87%) used for ST-segment elevation myocardial infarction. At 1 year, 6.2% had cardiovascular death, 15.8% MACE, 7.3% TLR and 1.5% ST. Cardiovascular death and MACE occurred less frequently in DES groups. The TLR rate was not significantly different in the CRF groups (BMS 9.8% vs DES 7.1%; P=0.44). No excess of ST was observed in the DES groups and use of DES was independently associated with absence of MACE and TLR. CONCLUSIONS: In patients with CRF, DES appear to be at least as effective as BMS--despite a higher restenosis risk profile--with no excess of ST at 1 year.

24 Article Clinical, angiographic, and genetic factors associated with early coronary stent thrombosis. 2011

Cayla, Guillaume / Hulot, Jean-Sébastien / O'Connor, Stephen A / Pathak, Atul / Scott, Stuart A / Gruel, Yves / Silvain, Johanne / Vignalou, Jean-Baptiste / Huerre, Yves / de la Briolle, Axel / Allanic, Frédérick / Beygui, Farzin / Barthélémy, Olivier / Montalescot, Gilles / Collet, Jean-Philippe. ·Institut de Cardiologie, INSERM Unité Mixte de Recherche_S 937, Pitié-Salpêtrière Hospital, Paris, France. ·JAMA · Pubmed #22028352.

ABSTRACT: CONTEXT: Despite dual antiplatelet therapy, stent thrombosis remains a devastating and unpredictable complication of percutaneous coronary intervention (PCI). OBJECTIVE: To perform a sequential analysis of clinical and genetic factors associated with definite early stent thrombosis. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 10 centers in France between January 2007 and May 2010 among 123 patients undergoing PCI who had definite early stent thrombosis and DNA samples available, matched on age and sex with 246 stent thrombosis-free controls. MAIN OUTCOME MEASURE: Accuracy of early stent thrombosis prediction by 23 genetic variants. RESULTS: Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (adjusted odds ratio [OR], 1.99; 95% CI, 1.47-2.69), ABCB1 3435 TT genotype (adjusted OR, 2.16; 95% CI, 1.21-3.88), and ITGB3 PLA2 carriage (adjusted OR, 0.52; 95% CI, 0.28-0.95). Nongenetic independent correlates were acuteness of PCI (adjusted OR, 3.05; 95% CI, 1.54-6.07), complex lesions (American College of Cardiology/American Heart Association type C) (adjusted OR, 2.33; 95% CI, 1.40-3.89), left ventricular function less than 40% (adjusted OR, 2.25; 95% CI, 1.09-4.70), diabetes mellitus (adjusted OR, 1.82; 95% CI, 1.02-3.24), use of proton pump inhibitors (adjusted OR, 2.19; 95% CI, 1.29-3.75), and higher clopidogrel loading doses (adjusted OR, 0.73; 95% CI, 0.57-0.93). The discriminative accuracy of the clinical-only model was similar to that of a genetic-only model (area under the curve, 0.73 [95% CI, 0.67-0.78] vs 0.68 [95% CI, 0.62-0.74], respectively; P = .34). A combined clinical and genetic model led to a statistically significant increase in the discriminatory power of the model compared with the clinical-only model (area under the curve, 0.78 [95% CI, 0.73-0.83] vs 0.73 [95% CI, 0.67-0.78]; P = .004). CONCLUSIONS: This case-control study identified 3 genes (CYP2C19, ABCB1, and ITGB3) and 2 clopidogrel-related factors (loading dose and proton pump inhibitors) that were independently associated with early stent thrombosis. Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts.

25 Article FXIII-A Leu34 genetic variant in premature coronary artery disease: a genotype--phenotype case control study. 2011

Silvain, Johanne / Pena, Ana / Vignalou, Jean-Baptiste / Hulot, Jean-Sébastien / Galier, Sophie / Cayla, Guillaume / Bellemain-Appaix, Anne / Barthélémy, Olivier / Beygui, Farzin / Bal-dit-Sollier, Claire / Drouet, Ludovic / Weisel, John W / Montalescot, Gilles / Collet, Jean-Phillippe. ·Institut de Cardiologie, INSERM UMRS 937, Pitié-Salpêtrière Hospital, AP-HP, Université Paris 6, Paris, France. ·Thromb Haemost · Pubmed #21800001.

ABSTRACT: The FXIII-A Leu34 genetic variant increases and accelerates fibrin stabilisation; however, its association with premature coronary artery disease (CAD) and thrombotic events remains controversial. FXIII Val34Leu genotype was determined in 242 young individuals (<45 years old) who survived a myocardial infarction (MI) and 242 healthy controls matched for age and gender. We evaluated its effect on long-term clinical outcome defined as a composite of cardiovascular death, recurrent MI and urgent revascularisation. In addition, fibrin clot stiffness (elastic modulus or EM) and response to rt-PA-mediated fibrinolysis (fibrinolysis rate) were measured ex vivo using the Hemodyne analyser and confocal microscopy as surrogate endpoint. FXIII-A Leu34 genetic variant was not associated with premature CAD (adj. odds ratio 0.83 [0.49-1.4]) nor did it influence clinical outcome in patients, during a median follow-up of 6.3 (± 2.4) years. Patients produced stiffer fibrin clots (median [IQR] EM = 20.3 [14.9-28.1] vs. 12.8 [9.6-17.1] kdynes/cm²; p<0.0001) and displayed reduced response to fibrinolysis with lower fibrinolysis rate (6.7 [3.4-11.0] vs. 9.0 [5.0-16.7] sec-¹ x 10(-4); p<0.0001) than healthy controls. Carriage of factor XIII-A Leu34 led to a stepwise decrease in fibrinolysis rate with a significant gene-dose-effect in patients (7.7 [4.1-12.2] vs. 4.8 [3.0-8.5] vs. 4.3 [2.4-8.1] sec-¹ x 10(-4), for wild-type, heterozygous and homozygous, p for trend = 0.003) and a non-significant trend in controls (p = 0.01). In conclusion, FXIII-A Leu34 is a polymorphism which provides a strong resistance to fibrinolysis with a gene-dose effect, but does not relate to premature CAD or to recurrent coronary events in this study.

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