title: Impact of obesity and the metabolic syndrome on response to clopidogrel or prasugrel and bleeding risk in patients treated after coronary stenting.
abstract: This study aimed to analyze the impact of body mass index (BMI) and the metabolic syndrome (MS) on responses to clopidogrel or prasugrel and bleeding risk after acute coronary syndrome. The study included 1,542 consecutive patients who underwent coronary stenting (287 clopidogrel 75 mg, 868 clopidogrel 150 mg, and 387 prasugrel 10 mg). Platelet reactivity was assessed 1 month after discharge using platelet reactivity index vasodilator stimulated phosphoprotein (PRI VASP). Three hundred thirty-six patients (21.8%) were obese (BMI ≥30), and we observed higher platelet reactivity associated with higher BMI across thienopyridine regimens. Incidence of high on-treatment platelet reactivity (PRI VASP >50%) was higher in obese than nonobese patients (p <0.05 for all regimens). Conversely, incidence of low on-treatment platelet reactivity with prasugrel therapy (PRI VASP <20%) was lower in obese than nonobese patients: 13% (12 of 93) versus 33% (97 of 294); odds ratio 0.30, 95% confidence interval 0.16 to 0.58; p <0.001. Accordingly, incidence of Bleeding Academic Research Consortium bleeding complications was higher in nonobese than in obese patients: 10% (119 of 1,206) versus 6% (20 of 336); odds ratio 1.7, 95% confidence interval 1.1 to 2.8; p = 0.03. This impaired response was only observed in obese patients with the MS, and obese with the MS had significantly higher platelet reactivity than other obese patients with all regimens (p <0.01). Obese patients without the MS had no significant difference in platelet reactivity compared with nonobese patients. In conclusion, the present study confirmed that BMI has a strong impact on response to clopidogrel and prasugrel with higher incidence of high on-treatment platelet reactivity, lower incidence of low on-treatment platelet reactivity, and lower bleeding complication in obese patients. However, among obese patients, the presence of the MS strongly affects response to antiplatelet agents, indicating that the metabolic status might be a better predictor of platelet inhibition than BMI.
authors.affiliation: Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Pankert
authors.affiliation: Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Quilici
authors.affiliation: Assistance Publique-Hôpitaux de Marseille-Unité d'Aide Méthodologique à la Recherche clinique, Marseille, France.
authors.forename: Anderson Diendonné
authors.initials: AD
authors.lastname: Loundou
authors.affiliation: Assistance Publique-Hôpitaux de Marseille-Equipe Mobile d'Aide à l'Investigation, Marseille, France.
authors.forename: Valentine
authors.initials: V
authors.lastname: Verdier
authors.affiliation: Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lambert
authors.affiliation: Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Deharo
authors.affiliation: Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bonnet
authors.affiliation: Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Gaborit
authors.affiliation: Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France; Laboratoire d'Hématologie, Centre Hospitalo-Universitaire Timone, Marseille, France.
authors.forename: Pierre Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.affiliation: Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France; Département de Nutrition, Maladies Métaboliques, Endocrinologie, Centre Hospitalo-Universitaire Timone, Marseille, France.
authors.forename: René
authors.initials: R
authors.lastname: Valéro
authors.affiliation: Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dutour
authors.affiliation: Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bonnet
authors.affiliation: Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France; Laboratoire d'Hématologie, Centre Hospitalo-Universitaire Timone, Marseille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.affiliation: Département de Cardiologie, Centre Hospitalo-Universitaire Timone, Marseille, France; Aix-Marseille Univ, Institut national de la santé et de la recherche médicale, Unité Mixte de Recherche 1062, Institut national de la recherche agronomique, Unité Mixte de Recherche 1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, Marseille, France. Electronic address: thomas.cuisset@ap-hm.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuisset
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy / Q000601:surgery*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D062645:Percutaneous Coronary Intervention / Q000379:methods; D010879:Piperazines / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019106:Postoperative Hemorrhage / Q000453:epidemiology* / Q000209:etiology; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D012189:Retrospective Studies; D015607:Stents; D013876:Thiophenes / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014481:United States / Q000453:epidemiology
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine