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1. Research into New Molecular Mechanisms in Thrombotic Diseases Paves the Way for Innovative Therapeutic Approaches

Author

Sara Sacchetti, Chiara Puricelli, Marco Mennuni, Valentina Zanotti, Luca Giacomini, Mara Giordano, Umberto Dianzani, Giuseppe Patti, and Roberta Rolla

Subjects
atherosclerotic plaque, coagulation cascade, platelets, extracellular vesicles, genetic factors, inflammation, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Thrombosis is a multifaceted process involving various molecular components, including the coagulation cascade, platelet activation, platelet–endothelial interaction, anticoagulant signaling pathways, inflammatory mediators, genetic factors and the involvement of various cells such as endothelial cells, platelets and leukocytes. A comprehensive understanding of the molecular signaling pathways and cell interactions that play a role in thrombosis is essential for the development of precise therapeutic strategies for the treatment and prevention of thrombotic diseases. Ongoing research in this field is constantly uncovering new molecular players and pathways that offer opportunities for more precise interventions in the clinical setting. These molecular insights into thrombosis form the basis for the development of targeted therapeutic approaches for the treatment and prevention of thrombotic disease. The aim of this review is to provide an overview of the pathogenesis of thrombosis and to explore new therapeutic options.

Published
2024
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2. Reduction in heart failure hospitalization rate during coronavirus disease 19 pandemic outbreak

Author

Paolo Severino, Andrea D'Amato, Andrea Saglietto, Fabrizio D'Ascenzo, Claudia Marini, Marco Schiavone, Nicolò Ghionzoli, Filippo Pirrotta, Francesca Troiano, Margherita Cannillo, Marco Mennuni, Andrea Rognoni, Francesco Rametta, Alessandro Galluzzo, Gianluca Agnes, Fabio Infusino, Mariateresa Pucci, Carlo Lavalle, Luca Cacciotti, Paul J. Mather, Walter Grosso Marra, Fabrizio Ugo, Giovanni Forleo, Maurizio Viecca, Nuccia Morici, Giuseppe Patti, Gaetano M. De Ferrari, Alberto Palazzuoli, Massimo Mancone, and Francesco Fedele

Subjects
Heart failure, COVID‐19, Hospitalization, Pandemic, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims The recent coronavirus disease 19 (COVID‐19) pandemic outbreak forced the adoption of restraint measures, which modified the hospital admission patterns for several diseases. The aim of the study is to investigate the rate of hospital admissions for heart failure (HF) during the early days of the COVID‐19 outbreak in Italy, compared with a corresponding period during the previous year and an earlier period during the same year. Methods and results We performed a retrospective analysis on HF admissions number at eight hospitals in Italy throughout the study period (21 February to 31 March 2020), compared with an inter‐year period (21 February to 31 March 2019) and an intra‐year period (1 January to 20 February 2020). The primary outcome was the overall rate of hospital admissions for HF. A total of 505 HF patients were included in this survey: 112 during the case period, 201 during intra‐year period, and 192 during inter‐year period. The mean admission rate during the case period was 2.80 admissions per day, significantly lower compared with intra‐year period (3.94 admissions per day; incidence rate ratio, 0.71; 95% confidence interval [CI], 0.56–0.89; P = 0.0037), or with inter‐year (4.92 admissions per day; incidence rate ratio, 0.57; 95% confidence interval, 0.45–0.72; P

Published
2020
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3. Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Author

Augusto Di Castelnuovo, Simona Costanzo, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Marialaura Bonaccio, Raffaele Bruno, Roberto Cauda, Alessandro Gialluisi, Giovanni Guaraldi, Lorenzo Menicanti, Marco Mennuni, Ilaria My, Agostino Parruti, Giuseppe Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio G. Stefanini, Alessandra Vergori, Walter Ageno, Luca Aiello, Piergiuseppe Agostoni, Samir Al Moghazi, Rosa Arboretti, Filippo Aucella, Greta Barbieri, Martina Barchitta, Alessandro Bartoloni, Carolina Bologna, Paolo Bonfanti, Lucia Caiano, Laura Carrozzi, Antonio Cascio, Giacomo Castiglione, Mauro Chiarito, Arturo Ciccullo, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Crizia Colombo, Francesco Crosta, Giovanni Dalena, Chiara Dal Pra, Gian Battista Danzi, Damiano D'Ardes, Katleen de Gaetano Donati, Francesco Di Gennaro, Giuseppe Di Tano, Gianpiero D'Offizi, Tommaso Filippini, Francesco Maria Fusco, Carlo Gaudiosi, Ivan Gentile, Giancarlo Gini, Elvira Grandone, Gabriella Guarnieri, Gennaro L. F. Lamanna, Giovanni Larizza, Armando Leone, Veronica Lio, Angela Raffaella Losito, Gloria Maccagni, Stefano Maitan, Sandro Mancarella, Rosa Manuele, Massimo Mapelli, Riccardo Maragna, Lorenzo Marra, Giulio Maresca, Claudia Marotta, Franco Mastroianni, Maria Mazzitelli, Alessandro Mengozzi, Francesco Menichetti, Jovana Milic, Filippo Minutolo, Beatrice Molena, R. Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Emanuela Pasi, Annalisa Perroni, Francesco Petri, Biagio Pinchera, Carlo A. Pivato, Venerino Poletti, Claudia Ravaglia, Marco Rossato, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Laura Scorzolini, Raffaella Sgariglia, Paola Giustina Simeone, Michele Spinicci, Enrico Maria Trecarichi, Giovanni Veronesi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Elena Visconti, Laura Vocciante, Raffaele De Caterina, Licia Iacoviello, and The COVID-19 RISK and Treatments (CORIST) Collaboration

Subjects
COVID-19, SARS-CoV-2, darunavir, lopinavir, in-hospital mortality, Medicine (General), R5-920
Abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Published
2021
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4. Assessing Risk in Patients with Stable Coronary Disease: When Should We Intensify Care and Follow-Up? Results from a Meta-Analysis of Observational Studies of the COURAGE and FAME Era

Author

Umberto Barbero, Fabrizio D’Ascenzo, Freek Nijhoff, Claudio Moretti, Giuseppe Biondi-Zoccai, Marco Mennuni, Davide Capodanno, Marco Lococo, Michael J. Lipinski, and Fiorenzo Gaita

Subjects
Medicine, Science
Abstract

Background. A large number of clinical and laboratory markers have been appraised to predict prognosis in patients with stable angina, but uncertainty remains regarding which variables are the best predictors of prognosis. Therefore, we performed a meta-analysis of studies in patients with stable angina to assess which variables predict prognosis. Methods. MEDLINE and PubMed were searched for eligible studies published up to 2015, reporting multivariate predictors of major adverse cardiac events (MACE, a composite endpoint of death, myocardial infarction, and revascularization) in patients with stable angina. Study features, patient characteristics, and prevalence and predictors of such events were abstracted and pooled with random-effect methods (95% CIs). Major adverse cardiovascular event (MACE) was the primary endpoint. Results. 42 studies (104,559 patients) were included. After a median follow-up of 57 months, cardiovascular events occurred in 7.8% of patients with MI in 6.2% of patients and need for repeat revascularization (both surgical and percutaneous) in 19.5% of patients. Male sex, reduced EF, diabetes, prior MI, and high C-reactive protein were the most powerful predictors of cardiovascular events. Conclusions. We show that simple and low-cost clinical features may help clinicians in identifying the most appropriate diagnostic and therapeutic approaches within the broad range of outpatients presenting with stable coronary artery disease.

Published
2016
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5. Safety and Efficacy of Selective, Clopidogrel-Based Strategies in Acute Coronary Syndrome: A Study-Level Meta-analysis

Author

Giuseppe Patti, Leonardo Grisafi, Enrico Guido Spinoni, Andrea Rognoni, and Marco Mennuni

Subjects
Ticagrelor, Percutaneous Coronary Intervention, Treatment Outcome, Humans, Hemorrhage, cardiovascular diseases, Hematology, Acute Coronary Syndrome, Prasugrel Hydrochloride, Platelet Aggregation Inhibitors, Clopidogrel
Abstract

Objectives To investigate outcomes with selective, clopidogrel-based therapies versus conventional treatment in patients undergoing percutaneous coronary intervention (PCI), especially for acute coronary syndrome. Background Safety and efficacy of alternative, selective, clopidogrel-based therapies after PCI are not robustly established. Methods We performed a study-level meta-analysis on six randomized trials investigating selective clopidogrel-based therapies (three on unguided de-escalation, N = 3,473; three on guided clopidogrel therapy, N = 7,533). Control groups received ticagrelor or prasugrel treatment. Main endpoints were major bleeding, any bleeding, major adverse cardiovascular events (MACE), and net clinical endpoint. Results The incidence of major bleeding and MACE was similar in the selective, clopidogrel-based therapy versus the conventional treatment arm (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.51–1.01, p = 0.06; OR: 0.93, 0.72–1.20, p = 0.58; respectively). The rates of any bleeding were lower in the selective, clopidogrel-based therapy versus conventional treatment group (OR: 0.57, 95% CI: 0.40–0.80, p = 0.001); this greater safety was significant for unguided de-escalation (OR: 0.43, 95% CI: 0.32–0.58, p = 0.00001) and nonsignificant for guided clopidogrel therapy (OR: 0.72, 95% CI: 0.51–1.02, p = 0.07; p for interaction: 0.03). The incidence of the net clinical endpoint was fewer in the selective, clopidogrel-based therapy versus the conventional treatment arm (OR: 0.59, 95% CI: 0.41–0.85, p = 0.004); this benefit was significant for unguided de-escalation (OR: 0.50, 95% CI: 0.39–0.64, p Conclusion As compared with prasugrel/ticagrelor treatment, alternative, selective, clopidogrel-based approaches provide a similar protection from cardiovascular events, reduce the risk of any bleeding, and are associated with a greater net benefit. These beneficial effects were prevalent with unguided de-escalation to clopidogrel.

Published
2022

6. 614 PREDICTIVE ROLE OF ECHOCARDIOGRAPHIC PULMONARY TO LEFT ATRIAL RATIO FOR IN-HOSPITAL DEATH IN PATIENTS WITH COVID-19

Author

Giovanni Pizzoferrato, Daniele Esposto, Angela Alberani, Katia Falasca, Jacopo Vecchiet, Marco Mennuni, Giuseppe Patti, Sabina Gallina, and Giulia Renda

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background and aims Echocardiographic Pulmonary to Left Atrial ratio (ePLAR, tricuspid regurgitation Vmax/mitral E/e') represents an accurate and sensitive non-invasive tool to estimate trans-pulmonary pressure gradient, showing a sensitivity for pre-capillary pulmonary obstruction higher than traditional echocardiographic measures. The prognostic value of ePLAR in patients with coronavirus disease-2019 (COVID-19) remains unknown. We aimed to investigate the predictive role of ePLAR on mortality in COVID-19 patients. Methods One hundred consecutive patients admitted in two Italian institutions for COVID-19 undergoing early echocardiographic examination were included. ePLAR was determined from the maximum tricuspid regurgitation velocity at continuous wave Doppler (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e′-wave ratio (TRVmax/E:e′). Main outcome measure was in-hospital death. Results Patients who died during hospitalization had a higher prevalence of tricuspid regurgitation, higher ePLAR and right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/Pulmonary Artery Systolic Pressure (PASP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR >0.28 m/s showed increased in-hospital mortality compared to those having ePLAR ≤0.28 m/s (27% vs 10.8%, p=0.05, Figure). A Cox model of multivariate analysis demonstrated that an ePLAR >0.28 m/s was independently associated with increased risk of death (HR 5.07, 95% CI 1.04-24.50, p=0.043), particularly among patients with increased pulmonary arterial pressure. Conclusions A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially to guide strategies of diagnosis and treatment.

Published
2022

7. Predictors of Mortality and Cardiovascular Outcome at 6 Months after Hospitalization for COVID-19

Author

Giulia Renda, Fabrizio Ricci, Enrico Guido Spinoni, Leonardo Grisafi, Damiano D’Ardes, Marco Mennuni, Claudio Tana, Andrea Rognoni, Mattia Bellan, Pier Paolo Sainaghi, Mario Pirisi, Simona De Vecchi, Sabina Gallina, Sante Donato Pierdomenico, Francesco Cipollone, and Giuseppe Patti

Subjects
cardiovascular events, COVID-19, follow-up, mortality, Medicine, General Medicine
Abstract

Clinical outcome data of patients discharged after Coronavirus disease 2019 (COVID-19) are limited and no study has evaluated predictors of cardiovascular prognosis in this setting. Our aim was to assess short-term mortality and cardiovascular outcome after hospitalization for COVID-19. A prospective cohort of 296 consecutive patients discharged after COVID-19 from two Italian institutions during the first wave of the pandemic and followed up to 6 months was included. The primary endpoint was all-cause mortality. The co-primary endpoint was the incidence of the composite outcome of major adverse cardiac and cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, pulmonary embolism, acute heart failure, or hospitalization for cardiovascular causes). The mean follow-up duration was 6 ± 2 months. The incidence of all-cause death was 4.7%. At multivariate analysis, age was the only independent predictor of mortality (aHR 1.08, 95% CI 1.01–1.16). MACCE occurred in 7.2% of patients. After adjustment, female sex (aHR 2.6, 95% CI 1.05–6.52), in-hospital acute heart failure during index hospitalization (aHR 3.45, 95% CI 1.19–10), and prevalent atrial fibrillation (aHR 3.05, 95% CI 1.13–8.24) significantly predicted the incident risk of MACCE. These findings may help to identify patients for whom a closer and more accurate surveillance after discharge for COVID-19 should be considered.

Published
2022

8. 286 Incidence of pocket haematoma with different anticoagulation strategies in patients undergoing cardiac implantable device implant or revision

Author

Enrico Guido Spinoni, Matteo Santagostino, Simona Costantino, Eleonora Battistini, Gabriele Dell’Era, Stefano Porcellini, Federica De Vecchi, Marco Mennuni, and Giuseppe Patti

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Aims Direct oral anticoagulants (DOACs) are known for lower bleeding risk than vitamin K antagonist (VKA) in patients with atrial fibrillation (AF). To date, it has not been established whether in such population DOAC may offer reduction of bleeding complication in patients undergoing cardiac implantable electronic device (CIED) implant or revision (substitution, upgrade, or downgrade). We evaluated whether DOACs compared to VKAs, decrease bleeding complications at the time of CIED implant in patients with AF, requiring oral anticoagulant therapy. Methods and results We present a monocentric observational retrospective study. Patients undergoing implant, generator replacement, or upgrading/downgrading of an intracardiac device (PM, ICD, or CRT) between January 2015 and March 2021 with AF undergoing DOAC or VKA were included. The comparison of risk of clinically significant pocket hematoma at 30-days follow-up in the two-treatment group [DOAC vs. VKA and DOAC vs. VKA without low molecular weight eparin (LMWH) bridge] was performed. Cox proportional hazards regression analysis including main clinical findings was performed to test the primary endpoint. Propensity score matching analysis was performed, with inversed proportional weighted (IPW) propensity score included in the multivariate analysis. 311 patients were included, 146 (46.9%) treated with DOAC and 165 (53.1%) treated with VKA. The incidence pocket haematoma was significantly reduced in patients treated with DOAC compared with VKA (3.4% vs. 13.3%, respectively, P = 0.002), a finding confirmed on multivariate analysis (HR: 3.02, CI: 1.10–8.29, P = 0.032). The incidence of pocket haematoma in patients on DOAC vs. VKA without LMWH bridge therapy was found to be significantly higher in the latter group of patients (P = 0.033, HR: 2.93, CI: 1.01–8.49, P = 0.48). After adjusting at propensity score with IPW, DOAC use showed decreased risk of pocket haematoma (HR: 0.29, CI: 0.09–0.95, P = 0.42). Conclusions In patients with atrial fibrillation undergoing CIED implant or revision, DOAC therapy appears to be associated with lower risk of event-related pocket haematoma at 30-day follow-up, even in the absence of bridging with LWMH. Such findings are hypothesis-generating.

Published
2021

9. Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial

Author

Johanne Silvain, Benoit Lattuca, Farzin Beygui, Grégoire Rangé, Zuzana Motovska, Jean-Guillaume Dillinger, Ziad Boueri, Philippe Brunel, Thibault Lhermusier, Christophe Pouillot, Elisa Larrieu-Ardilouze, Franck Boccara, Jean-Noël Labeque, Paul Guedeney, Mohamad El Kasty, Mikael Laredo, Raphaëlle Dumaine, Grégory Ducrocq, Jean-Philippe Collet, Guillaume Cayla, Katrien Blanchart, Petr Kala, Eric Vicaut, Gilles Montalescot, Johanne SILVAIN, Jean-Philippe COLLET, Gilles MONTALESCOT, Mathieu KERNEIS, Nassim BRAIK, Olivier BARTHELEMY, Gérard HELFT, Claude LEFEUVRE, Rémi CHOUSSAT, Marie HAUGUEL, Michel ZEITOUNI, Thomas CUISSET, Jean-Louis BONNET, Pierre DEHARO, Benoit LATTUCA, Guillaume CAYLA, Luc CORNILLET, Bertrand LEDERMANN, Clément LONJON, Laurent SCHMUTZ, Grégoire RANGE, Franck ALBERT, Thibault DEMICHELI, Laurent ROUSSEL, Reda BENSAID, Christophe THUAIRE, Jean-Guillaume DILLINGER, Patrick HENRY, Stéphane MANZO-SILBERMAN, Georgios SIDERIS, Damien LOGEART, Vincent SPAGNOLI, Léa CACOUB, Christophe POUILLOT, Jean Richard VI-FANE, Jens GLASENAPP, Karim BOUGRINI, Nicolas COMBARET, Pascal MOTREFF, Géraud SOUTEYRAND, Aimé AMONCHOT, Thomas MOUYEN, Thibault LHERMUSIER, Didier CARRIE, Frédéric BOUISSET, Thomas CHOLLET, Francisco CAMPELO-PARADA, Nicolas DELARCHE, François SCHIELE, Mathieu BESUTTI, Marie HAUGUEL-MOREAU, Rami EL MAHMOUD, Christophe CAUSSIN, Mami ZOHEIR, Aurelie VEUGEOIS, Alain DIBIE, Olivier VARENNE, Fabien PICARD, Alexandre LAFONT, Julien ADJEDJ, Philippe DEGRELL, Farzin BEYGUI, Rémi SABATIER, Vincent ROULE, Mathieux BIGNON, Katrien BLANCHART, Pierre ARDOUIN, Adrien LEMAITRE, Clément BRIET, Ziad BOUERI, Pascal GOUBE, Pierre COSTE, Laura CETRAN, Jérôme CLERC, Hervé LE BRETON, Dominique BOULMIER, Vincent AUFFRET, Jean-Noël LABEQUE, Jean-Luc BONAS, Jean-Louis GEORGES, Bernard LIVAREK, Elodie BLICQ, Nicolas BARON, Géraldine GIBAULT-GENTY, Yves COTTIN, Isabelle LHUILLIER, Carole RICHARD, Luc LORGIS, Philippe BUFFET, Christian SPAULDING, Nicole KARAM, Etienne PUYMIRAT, Marco MENNUNI, Emmanuel POULIDAKIS, Lionel BONNEVIE, Franck BOCCARA, Marion CHAUVET, Laurie DUFOUR, Yann ANCEDY, Stéphane EDERHY, Arnaud ETIENNEY, Anne BELLEMAIN-APPAIX, Nathaniel BITTON, Laurent JACQ, Christophe SAINT-ETIENNE, Florence LECLERCQ, François ROUBILLE, Gilles RIOUFOL, François DERIMAY, Marc GORALSKI, Wael YAFI, Emmanuelle FILIPPI, Alain KERMARREC, Christophe LE RAY, Antoine MERLET, Aurelie LOIRAT, Philippe BRUNEL, Damien BRUNET, Jack RAVISY, Laurent MOCK, Guillaume MOLINS, Max CARRE, Erwan BRESSOLLETTE, Luc CHRISTIAENS, Elisa LARRIEU-ARDILOUZE, Romain CADOR CADOR, Eric VAN BELLE, Gilles LEMESLE, Cédric DELHAYE, Flavien VINCENT, Sina POROUCHANI, Hugues SPILLEMAEKER, Katy PETIT, Olivier RESSENCOURT, Vincent HUMEAU, François JOURDA, Marc-Antoine ARNOULD, Stephen CHASSAING, Karl ISAAZ, Laurent PAYOT, Jacques MONTSEGU, Benjamin FAURIE, Michel PANSIERI, Marc METGE, Karim MOUSSA, Mathieu PANKERT, Olivier MOREL, Sébastien HESS, Luc MAILLARD, Thibault MANIGOLD, Vincent LETOCART, Julien PLESSIS, Pauline BERTHOME, Mickael BONIN, François HUCHET, Emmanuel TEIGER, Romain GALLET, Gauthier MOUILLET, Madjid BOUKANTAR, Mohammed NEJJARI, David ATTIAS, Mathieu STEINECKER, Zuzana MOTOVSKA, Martin KOZEL, Zdenko STELMACH, Ota HLINOMAZ, Michal REZEK, Martin NOVAK, Jan SITAR, Jiri SEMENKA, Petr KALA, Otakar BOCEK, Roman ŠTIPAL, Martin POLOCZEK, Jan KANOVSKÝ, Petr JERABEK, Jiří KARASEK, Sylvie HRUSKOVA, Marian BRANNY, Jan MROZEK, Tomas GREZL, Leos PLEVA, Pavel KUKLA, Martin PORZER, Lesnik, Philippe, Institut de cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de cardiologie et de pathologie vasculaire [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Louis Pasteur [Chartres], Charles University [Prague] (CU), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Bastia (G2HC), Service de Cardiologie [Hôpital privé Dijon Bourgogne], Hôpital privé Dijon Bourgogne, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Clinique Sainte Clotilde, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Le CHCB, Centre Hospitalier de la Côte Basque, Grand Hôpital de l'Est Francilien (GHEF), Centre de Réadaptation Cardiaque Les Grands Prés [Villeneuve Saint Denis] (CRCLGP), Service de cardiologie [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot, Sorbonne Paris Cité, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), University Hospital Brno, Masaryk University [Brno] (MUNI), Hopital Saint-Louis [AP-HP] (AP-HP), Erasmus University Medical Center [Rotterdam] (Erasmus MC), ALPHEUS investigators: Johanne Silvain, Jean-Philippe Collet, Gilles Montalescot, Mathieu Kerneis, Nassim Braik, Olivier Barthelemy, Gérard Helft, Claude Lefeuvre, Rémi Choussat, Marie Hauguel, Michel Zeitouni, Thomas Cuisset, Jean-Louis Bonnet, Pierre Deharo, Benoit Lattuca, Guillaume Cayla, Luc Cornillet, Bertrand Ledermann, Clément Lonjon, Laurent Schmutz, Grégoire Range, Franck Albert, Thibault Demicheli, Laurent Roussel, Reda Bensaid, Christophe Thuaire, Jean-Guillaume Dillinger, Patrick Henry, Stéphane Manzo-Silberman, Georgios Sideris, Damien Logeart, Vincent Spagnoli, Léa Cacoub, Christophe Pouillot, Jean Richard Vi-Fane, Jens Glasenapp, Karim Bougrini, Nicolas Combaret, Pascal Motreff, Géraud Souteyrand, Aimé Amonchot, Thomas Mouyen, Thibault Lhermusier, Didier Carrie, Frédéric Bouisset, Thomas Chollet, Francisco Campelo-Parada, Nicolas Delarche, François Schiele, Mathieu Besutti, Marie Hauguel-Moreau, Rami El Mahmoud, Christophe Caussin, Mami Zoheir, Aurelie Veugeois, Alain Dibie, Olivier Varenne, Fabien Picard, Alexandre Lafont, Julien Adjedj, Philippe Degrell, Farzin Beygui, Rémi Sabatier, Vincent Roule, Mathieux Bignon, Katrien Blanchart, Pierre Ardouin, Adrien Lemaitre, Clément Briet, Ziad Boueri, Pascal Goube, Pierre Coste, Laura Cetran, Jérôme Clerc, Hervé LE Breton, Dominique Boulmier, Vincent Auffret, Jean-Noël Labeque, Jean-Luc Bonas, Jean-Louis Georges, Bernard Livarek, Elodie Blicq, Nicolas Baron, Géraldine Gibault-Genty, Yves Cottin, Isabelle Lhuillier, Carole Richard, Luc Lorgis, Philippe Buffet, Christian Spaulding, Nicole Karam, Etienne Puymirat, Marco Mennuni, Emmanuel Poulidakis, Lionel Bonnevie, Franck Boccara, Marion Chauvet, Laurie Dufour, Yann Ancedy, Stéphane Ederhy, Arnaud Etienney, Anne Bellemain-Appaix, Nathaniel Bitton, Laurent Jacq, Christophe Saint-Etienne, Florence Leclercq, François Roubille, Gilles Rioufol, François Derimay, Marc Goralski, Wael Yafi, Emmanuelle Filippi, Alain Kermarrec, Christophe LE Ray, Antoine Merlet, Aurelie Loirat, Philippe Brunel, Damien Brunet, Jack Ravisy, Laurent Mock, Guillaume Molins, Max Carre, Erwan Bressollette, Luc Christiaens, Elisa Larrieu-Ardilouze, Romain Cador Cador, Eric VAN Belle, Gilles Lemesle, Cédric Delhaye, Flavien Vincent, Sina Porouchani, Hugues Spillemaeker, Katy Petit, Olivier Ressencourt, Max Carre, Vincent Humeau, François Jourda, Marc-Antoine Arnould, Stephen Chassaing, Karl Isaaz, Laurent Payot, Jacques Montsegu, Benjamin Faurie, Michel Pansieri, Marc Metge, Karim Moussa, Mathieu Pankert, Olivier Morel, Sébastien Hess, Luc Maillard, Thibault Manigold, Vincent Letocart, Julien Plessis, Pauline Berthome, Mickael Bonin, François Huchet, Emmanuel Teiger, Romain Gallet, Gauthier Mouillet, Madjid Boukantar, Rami El Mahmoud, Mohammed Nejjari, David Attias, Léa Cacoub, Mathieu Steinecker, François Huchet, Zuzana Motovska, Martin Kozel, Zdenko Stelmach, Ota Hlinomaz, Michal Rezek, Martin Novak, Jan Sitar, Jiri Semenka, Petr Kala, Otakar Bocek, Roman Štipal, Martin Poloczek, Jan KanovskÝ, Petr Jerabek, Jiří Karasek, Sylvie Hruskova, Marian Branny, Jan Mrozek, Tomas Grezl, Leos Pleva, Pavel Kukla, Martin Porzer., Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, Ticagrelor, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, Coronary artery disease, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, Percutaneous coronary intervention, General Medicine, Middle Aged, medicine.disease, Clopidogrel, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Action study, Elective Surgical Procedures, Anesthesia, Conventional PCI, Purinergic P2Y Receptor Antagonists, Female, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

International audience; Background: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI.Methods: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290.Findings: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070).Interpretation: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI.Funding: ACTION Study Group and AstraZeneca.

Published
2020

10. Contribution of Atrial Fibrillation to In-Hospital Mortality in Patients With COVID-19

Author

Enrico Guido Spinoni, Marco, Mennuni, Andrea, Rognoni, Leonardo, Grisafi, Crizia, Colombo, Veronica, Lio, Giulia, Renda, Melissa, Foglietta, Ivan, Petrilli, Damiano, D’Ardes, Pier Paolo Sainaghi, Gianluca, Aimaretti, Mattia, Bellan, Luigi, Castello, Gian Carlo Avanzi, Francesco Della Corte, Krengli, Marco, Mario, Pirisi, Mario, Malerba, Andrea, Capponi, Sabina, Gallina, Sante Donato Pierdomenico, Francesco, Cipollone, Giuseppe, Patti, the COVID-UPO Clinical Team, Emanuele, Albano, Umberto, Dianzani, Gianluca, Gaidano, Alessandra, Gennari, Carla, Gramaglia, Martina, Solli, Ailia, Giubertoni, Alessia, Veia, Carlo, Cisari, Paolo Amedeo Tillio, Paolo Aluffi Valletti, BARONE ADESI, Francesco, Michela, Barini, Ferrante, Daniela, Simona De Vecchi, Matteo, Santagostino, Antonio, Acquaviva, Elisa, Calzaducca, Francesco Giuseppe Casciaro, Federico, Ceruti, Micol Giulia Cittone, Davide Di Benedetto, Ileana, Gagliardi, Greta Maria Giacomini, Irene Cecilia Landi, Raffaella, Landi, Giulia Francesca Manfredi, Anita Rebecca Pedrinelli, Cristina, Rigamonti, Eleonora, Rizzi, Carlo, Smirne, Veronica, Vassia, Roberto, Arioli, Pietro, Danna, Zeno, Falaschi, Alessio, Paschè, Ilaria, Percivale, Domenico, Zagaria, Michela, Beltrame, Matteo, Bertoli, Alessandra, Galbiati, Clara Ada Gardino, Maria Luisa Gastaldello, Valentina Giai Via, Francesca, Giolitti, Ilaria, Inserra, Emanuela, Labella, Ilaria, Nerici, Laura Cristina Gironi, Edoardo, Cammarata, Elia, Esposto, Vanessa, Tarantino, Elisa, Zavattaro, Francesca, Zottarelli, Tommaso, Daffara, Alice, Ferrero, Ilaria, Leone, Alessandro, Nuzzo, Giulia, Baldon, Sofia, Battistini, Emilio, Chirico, Luca, Lorenzini, Maria, Martelli, Emanuela, Barbero, Paolo, Boffano, Matteo, Brucoli, Massimiliano, Garzaro, Alberto, Pau, Stephanie, Bertolin, Letizia, Marzari, Gianluca, Avino, Massimo, Saraceno, Umberto, Morosini, Alessio, Baricich, Marco, Invernizzi, Silvia, Gallo, Claudia, Montabone, Samuel Alberto Padelli, Lucio, Boglione, Filippo, Patrucco, Luigia, Salamina, Francesca, Baorda, Eleonora, Croce, and Irene, Giacone.

Subjects
Male, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Risk Assessment, Risk Factors, Physiology (medical), Atrial Fibrillation, Research Letter, medicine, Humans, In patient, Hospital Mortality, hospital, Risk factor, Retrospective Studies, In hospital mortality, business.industry, COVID-19, Atrial fibrillation, Retrospective cohort study, Prognosis, medicine.disease, atrial fibrillation, mortality, risk factor, Female, Hospitalization, Italy, Emergency medicine, Cardiology and Cardiovascular Medicine, Risk assessment, business
Published
2021

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