Publications (17)66.63 Total impact
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Article: Effect of CYP2C19*2 and *17 Genetic Variants on Platelet Response to Clopidogrel and Prasugrel Maintenance Dose and Relation to Bleeding Complications.
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ABSTRACT: The present study was performed to compare the influence of cytochrome P459 2C19 (CYP2C19) *2 and *17 genetic variants on the platelet response to clopidogrel and prasugrel maintenance therapy and to assess the relation between platelet reactivity and bleeding complications. A total of 730 patients were included (517 patients treated with clopidogrel 150 mg/day and 213 discharged with prasugrel 10 mg). Platelet reactivity was assessed at 1 month with the platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP). High on-treatment platelet reactivity was defined as PRI VASP >50% and low on-treatment platelet reactivity (LTPR) as PRI VASP <20%. The patients were classified according to their genotypes as poor metabolizers (*2/non *17), intermediate metabolizers (*2/*17 or non *2/non *17) and ultrametabolizers (non *2/*17). At 1 month, the prasugrel response was significantly better than the clopidogrel response in all groups of patients, with a lower incidence of high on-treatment platelet reactivity but a greater incidence of LTPR, regardless of the genetic variants. The genetic distribution had a significant effect on the mean PRI VASP values, the incidence of high on-treatment platelet reactivity, and LTPR with both clopidogrel and prasugrel (p <0.05 for all). LTPR identified a group of patients at a greater risk of bleeding (odds ratio 4.8, 95% confidence interval 2.7 to 8.3; p <0.0001). In conclusion, the present study showed that both clopidogrel and prasugrel have genetic modulation by CYP2C19 *2 and *17 alleles and that prasugrel provides greater platelet inhibition, regardless of the genotypes. In addition, LTPR was associated with a greater risk of bleeding.The American journal of cardiology 01/2013; · 3.58 Impact Factor -
Article: Usefulness of index of microcirculatory resistance to detect microvascular dysfunction as a potential mechanism of stress-induced cardiomyopathy (Tako-tsubo syndrome).
International journal of cardiology 03/2011; 153(3):e51-3. · 7.08 Impact Factor -
Article: Coronary wall characteristics after myocardial infarction without significant coronary angiographic lesion: an intravascular ultrasound study.
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ABSTRACT: Coronary of angiography may be normal or without significant lesion after myocardial infarction (MI) in about 10% of cases. Our aim was to evaluate intravascular ultrasound (IVUS) findings, mainly remodelling, in patients with normal or near normal angiography early after MI. We prospectively included 17 patients, admitted for STEMI or non-STEMI with no lesion > 30% (QCA) on early coronary angiography. Culprit vessel was defined by evidence of a thrombus in a proximal segment, distal embolization or focal akinesia of the left ventricle. Negative remodelling (NR) was defined as a remodelling index (lesion/reference external elastic membrane cross sectional area [CSA]) < 0.95, no remodelling as between 0.95-1.05, and positive remodelling (PR) as > 1.05. IVUS could identify a short, single, minor, eccentric and hypoechogenic lesion in all patients, of proximal location in 76.4% cases. PR was observed in only 1 patient (5.9%). A discrete lesion was observed in all patients with apparently normal arteries. Although previous reports have shown an association between PR and vulnerability, in our study PR was unusual. Our study supports the hypothesis that in some patients, vulnerability may appear very early in the natural history of coronary artery disease before any vessel remodelling.Acta cardiologica 12/2010; 65(6):627-30. · 0.61 Impact Factor -
Article: Clopidogrel response: head-to-head comparison of different platelet assays to identify clopidogrel non responder patients after coronary stenting.
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ABSTRACT: We investigated the agreement between different platelet tests to identify clopidogrel non response. Biological definition of clopidogrel non response remains controversial. Different platelet tests have been linked with recurrent ischemic events and proposed for daily practice. We prospectively investigated the agreement of platelet tests to isolate clopidogrel non response in patients receiving high 150 mg clopidogrel maintenance dose after coronary stenting. Clopidogrel response was assessed with ADP-induced aggregation (ADP-Ag) (non response if >70%), Platelet reactivity index VASP (PRI VASP) (non response if >50%) and Verify Now Point-of-care assay (VN) (non response if PRU > 240 AU). Seventy consecutive patients were included. The rates of non-responders were respectively: 13% (n = 9) with the ADP-Ag, 39% (n = 27) with the PRI VASP and 33% (n = 23) with the VN. We observed significant correlation between different platelet tests assessing clopidogrel response: r = 0.55 (p < 0.0001) for ADP-Ag and PRI VASP, r = 0.64 (p < 0.0001) for ADP-Ag and VN and r = 0.59 (p < 0.0001) for PRI VASP and VN. However, using the most common thresholds, the agreement between the difference tests was poor: 0.35 for ADP-Ag and PRI VASP, 0.36 for ADP-Ag and VN and 0.46 for PRI VASP and VN. This study showed that assessment of platelet function inhibition by clopidogrel is highly test-specific. Indeed, our results demonstrated a poor agreement between different platelet assays and suggested that identification of clopidogrel non responders is test-dependent.Archives of cardiovascular diseases 01/2010; 103(1):39-45. · 0.66 Impact Factor -
Article: Effect of increased aspirin dose after stenting in association with ClOpidogrel: the FIASCO randomized study.
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ABSTRACT: Increased doses of antiplatelet therapy have been proposed to overcome the variability of response. However, the chronic dose of aspirin after DES remains controversial. We assessed in a prospective and randomized study the benefit of higher dose of aspirin, in association with clopidogrel, on aspirin response and non COX-specific platelet testing in patients receiving Drug Eluting Stent (DES) for stable angina pectoris. 50 consecutive patients receiving DES for stable angina pectoris were prospectively included. They received loading dose of 250 mg aspirin and 600 mg clopidogrel and antiplatelet response was assessed with Arachidonic Acid-induced aggregation (AA-Ag) and ADP-induced aggregation (ADP-Ag) for aspirin and clopidogrel response respectively. Patients were randomized to either 75 or 160 mg of aspirin with 150 mg clopidogrel and platelet testing were repeated one month after hospital discharge. The two groups (aspirin "75 mg" or "160 mg") had no difference for aspirin response: AA-Ag (5.2 +/- 1.7% vs 6 +/- 2%, p = 0.75) and non COX-specific pathway testing: ADP-Ag (47 +/- 3% vs 49 +/- 4%, p = 0.61). The present study did not show any benefit of higher dose of aspirin neither on aspirin responsiveness, nor on inhibition of non COX-specific pathway. These data does not support use of higher dose than 75 mg of aspirin in association with clopidogrel in patients receiving DES, especially while higher doses have been associated with increased bleeding risk.Thrombosis Research 12/2008; 124(1):33-6. · 2.44 Impact Factor -
Article: Glycoprotein IIb/IIIa inhibitors improve outcome after coronary stenting in clopidogrel nonresponders: a prospective, randomized study.
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ABSTRACT: The aim of this study was to assess, in clopidogrel nonresponders undergoing elective percutaneous coronary intervention (PCI), the benefit of adjusted antiplatelet therapy with glycoprotein (GP) IIb/IIIa antagonist administration during PCI for 1-month clinical outcome. Numerous biological studies have reported interindividual variability in platelet response to clopidogrel with clinical relevance, and high post-treatment platelet reactivity (adenosine diphosphate-induced aggregation >70%) has been proposed to define nonresponse to clopidogrel. These nonresponders might benefit from tailored antiplatelet therapy. One hundred forty-nine clopidogrel nonresponders referred for elective PCI were prospectively included and randomized to "conventional group" (n = 75) or "active group" with GP IIb/IIIa antagonist (n = 74). All patients received 250-mg aspirin and 600-mg clopidogrel before PCI and platelet testing. The rate of cardiovascular events at 1 month was significantly lower in the "active group" than in the "conventional group": 19% (n = 14) versus 40% (n = 30), p = 0.006, odds ratio: 2.8; 95% confidence interval: 1.4 to 6.0. No patient in either group had post-procedural Thrombolysis In Myocardial Infarction major bleeding or required transfusions. The present study suggested benefit of tailored antiplatelet therapy during elective PCI with GP IIb/IIIa antagonist for clopidogrel nonresponders without increased bleeding risk.12/2008; 1(6):649-53. · 1.07 Impact Factor -
Article: Prognostic value of ischaemia-modified albumin in patients with non-ST-segment elevation acute coronary syndromes.
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ABSTRACT: Ischaemia-modified albumin (IMA) is a new sensitive diagnostic biochemical marker of myocardial ischaemia. The purpose of the study was to analyse the prognostic value of IMA in patients admitted for non-ST-segment elevation acute coronary syndromes (NSTE ACS). Consecutive patients admitted for NSTE ACS in our institution were prospectively included. IMA, cardiac troponin I (TnI) and C-reactive protein (CRP) were measured in all patients within 3h of last chest pain. The clinical combined endpoint was major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction (MI) and recurrent ischaemia leading to urgent revascularization. The independent prognostic impact of IMA on occurrence of the combined endpoint during hospitalization and at 1 year was tested by a logistic regression model and was systematically adjusted for other known clinical and biological predictors. Seventy-nine patients were enrolled. Nine (11.4%) patients experienced the combined endpoint during hospitalization and 16 (20.2%) during 1-year follow-up. Median IMA level was significantly higher in patients with MACE during hospitalization (115 [93-126]U/mL versus 100 [42-138]U/mL; p=0.007) and at 1 year (114 [93-126]U/mL versus 97 [42-138]U/mL; p<0.001). After adjustment for conventional prognostic risk factors, IMA remained an independent predictor of MACE both during hospitalization (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.01-1.16; p=0.03) and at 1 year (hazards ratio [HR]: 1.07; 95% CI: 1.03-1.12; p=0.003). Baseline levels of IMA were associated with both short- and long-term cardiovascular (CV) events in patients admitted for NSTE ACS.Archives of Cardiovascular Diseases 11/2008; 101(10):645-51. · 1.51 Impact Factor -
Article: Relationship between aspirin and clopidogrel responses in acute coronary syndrome and clinical predictors of non response.
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ABSTRACT: We have prospectively investigated the association between aspirin and clopidogrel responses and the clinical predictors of non response. 635 Non ST Elevation Acute Coronary Syndrome (NSTE ACS) patients were included and received loading doses of 250 mg aspirin and 600 mg clopidogrel. We analyzed post-treatment maximal intensity of arachidonic acid and ADP-induced platelet aggregation (AA-Ag and ADP-Ag) and Platelet Reactivity Index of VAsodilator-Stimulated Phosphoprotein (PRI VASP). Aspirin and clopidogrel non responses were defined respectively by AA-Ag>30% and ADP-Ag>70%. Aspirin non responders patients had significantly higher ADP-Ag and PRI VASP than aspirin responders: 63.7+/-15.9% vs 55+/-19% (p=0.0001) and 73.6+/-13.3% vs 53+/-23% (p=0.0001) respectively and the rate of clopidogrel non responders was higher among aspirin non responders than aspirin responders: 36.7% vs 22.7% (p=0.003). In addition, clopidogrel non responders had significantly higher AA-Ag and rate of aspirin non responders than clopidogrel responders: 21.6+/-24% vs 10.3+/-19% (p=0.0001) and 22.8% vs 12.9% (p=0.003) respectively. Age and Body Mass Index (BMI) were significantly associated with non response to Clopidogrel (p=0.035 and 0.02 respectively) and diabetes mellitus by trend (p=0.07). We observed a relationship between aspirin and clopidogrel non responses and an association between age, BMI and diabetes mellitus and clopidogrel response.Thrombosis Research 05/2008; 123(4):597-603. · 2.44 Impact Factor -
Article: Diagnosis contribution of IVUS in embolic myocardial infarction.
International journal of cardiology 04/2008; 124(3):e47-8. · 7.08 Impact Factor -
Article: Effect of cytochrome p450 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndrome.
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ABSTRACT: Genetic polymorphisms of cytochrome P450 (CYP) isoforms may promote variability in platelet response to clopidogrel. This study was conducted to analyze, in 603 patients with non-ST elevation acute coronary syndromes, the effect of CYP3A4, CYP3A5, and CYP2C19 gene polymorphisms on clopidogrel response and post-treatment platelet reactivity assessed by adenosine diphosphate (ADP)-induced platelet aggregation, vasodilator-stimulated phosphoprotein phosphorylation index, and ADP-induced P-selectin expression. The CYP2C19*2 polymorphism was significantly associated with ADP-induced platelet aggregation, vasodilator-stimulated phosphoprotein phosphorylation index, and ADP-induced P-selectin expression in recessive (p <0.01, p <0.007, and p <0.06, respectively) and codominant (p <0.08, p <0.0001, and p <0.009, respectively) models, but the CYP3A4*1B and CYP3A5*3 polymorphisms were not. The CYP2C19*2 allele carriers exhibited the highest platelet index levels in multivariate analysis (p = 0.03). After covariate adjustment, the CYP2C19*2 allele was more frequent in clopidogrel nonresponders, defined by persistent high post-treatment platelet reactivity (ADP-induced platelet aggregation >70%; p = 0.03). In conclusion, the present data suggest that the CYPC19*2 allele influences post-treatment platelet reactivity and clopidogrel response in patients with non-ST elevation acute coronary syndromes.The American Journal of Cardiology 04/2008; 101(8):1088-93. · 3.37 Impact Factor -
Article: Eclipsed mitral regurgitation: a new form of functional mitral regurgitation for an unusual cause of heart failure with normal ejection fraction.
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ABSTRACT: Transient functional mitral regurgitation (MR) has never been reported as a cause of heart failure (HF) with normal ejection fraction (EF) in the absence of epicardial coronary artery stenosis. Performance of echocardiography in patients with acute HF before initiation of HF medical treatment allowed identification of three patients with normal EF but transient massive functional MR during the HF episode. In all patients, massive MR occurred as a consequence of sudden extreme apical tenting of both leaflets with total lack of coaptation, despite normal EF and absence of detectable left ventricular (LV) remodeling, and despite absence of significant stenosis on coronary arteries. In all patients MR was triggered by methylergonovine injection and was reversible either spontaneously or after nitroglycerine administration, leaving patients with normal echocardiogram between HF episodes. In two patients, long-term administration of calcium channel blockers prevented recurrences of MR and HF, whereas in one, mitral valve was eventually replaced. Sudden reversible apical tenting of mitral leaflets with subsequent torrential MR and acute HF can occur despite normal EF, absence of pre-existing LV remodeling and absence of coronary artery stenosis. This atypical type of functional MR is an unusual mechanism of HF in patients with normal LVEF.Cardiology 02/2008; 110(1):29-34. · 1.71 Impact Factor -
Article: ADP-induced platelet aggregation and platelet reactivity index VASP are good predictive markers for clinical outcomes in non-ST elevation acute coronary syndrome.
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ABSTRACT: Clopidogrel responsiveness has been proposed to be involved in recurrent ischemic events after stenting for non-ST elevation acute coronary syndromes (NSTE ACS). However, its biological definition is not consensual. We assess the value of ADP-induced platelet aggregation (ADP-Ag) and platelet reactivity index VASP (PRI VASP) in predicting recurrent ischemic events in patients with NSTE ACS undergoing percutaneous coronary intervention (PCI). We studied 195 consecutive NSTE ACS patients undergoing PCI after a 600 mg loading dose of clopidogrel. ADP-Ag and PRI VASP were analysed. The primary end-point was recurrent ischemic events within 30 days of PCI. It occurred in 14 patients (7%). Construction of ROC curves to examine the value of predictive models showed that sensitivity and specificity for primary endpoint were 79% and 76%, respectively, for a maximal intensity of ADP-Ag >or=70%, 93% and 50% for PRIVASP > 53%. The positive and negative predictive values were 21% and 98%, respectively, for ADP-Ag >or=70%, 12% and 99% for PRIVASP > 53%. In patients with NSTE ACS undergoing PCI, ADP-Ag and PRI VASP identify low responders to clopidogrel with an increased risk of recurrent ischemic events with respective cut-off values of 70% and 53%.Thrombosis and Haemostasis 11/2007; 98(4):838-43. · 5.04 Impact Factor -
Article: High post-treatment platelet reactivity is associated with a high incidence of myonecrosis after stenting for non-ST elevation acute coronary syndromes.
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ABSTRACT: High post-treatment platelet reactivity (HPPR=adenosine diphosphate [ADP] 10 microM-induced platelet aggregation >70%) identifies low responders to dual antiplatelet therapy with increased risk of recurrent cardiovascular (CV) events after stenting for non-ST elevation acute coronary syndromes (NSTE-ACS). This study was designed to compare the incidence of periprocedural myocardial infarction (MI) after stenting for NSTE-ACS patients between non-responders to dual antiplatelet therapy defined by HPPR and normo-responders. One hundred ninety NSTE-ACS consecutive patients undergoing coronary stenting were included in this prospective study. They received 250 mg aspirin and a 600 mg loading dose of clopidogrel at least 12 hours (h) before percutaneous coronary intervention (PCI). A single post-treatment blood sample was obtained before PCI to analyze maximal intensity of ADP-induced platelet aggregation, and troponin levels were analyzed before PCI, and 12 and 24 h after PCI. Troponin I was considered elevated if >0.4 ng/ml. HPPR was present in 22% of patients (n=42). Periprocedural MI occurred significantly more frequently in patients with HPPR than in the normo-responders (43% vs. 24%, p=0.014). After being correlated with recurrent ischemic events after stenting for NSTE-ACS, the HPPR seems to be also a marker of increased risk of periprocedural MI for NSTE-ACS patients.Thrombosis and Haemostasis 02/2007; 97(2):282-7. · 5.04 Impact Factor -
Article: Lack of association between the 807 C/T polymorphism of glycoprotein Ia gene and post-treatment platelet reactivity after aspirin and clopidogrel in patients with acute coronary syndrome.
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ABSTRACT: Variability in platelet response to antiplatelet therapy and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. It was the aim of the present study to assess whether the response to aspirin and clopidogrel may be influenced by the 807 C/T polymorphism of the glycoprotein Ia (GpIa) gene in patients with non-ST elevation acute coronary syndrome (NSTE ACS). Six hundred one NSTE ACS patients were included in our study and were divided into three groups: CC homozygotes, CT heterozygotes ad TT homozygotes. All patients received loading doses of 600 mg clopidogrel and 250 mg aspirin at least 12 hours before blood samples were drawn. Post-treatment platelet reactivity was assessed by post treatment ADP 10 microM-induced platelet aggregation (ADP-Ag), VASP phosphorylation (PRI VASP) and P-selectin expression. Non-response to dual antiplatelet therapy was defined by high post-treatment platelet reactivity (HPPR=ADP-Ag > 70%). Significant variability in the distribution of platelet parameters was observed in the overall study population. No significant difference in platelet parameters profiles was observed within patients having the same genotype, for ADP-Ag (p=0.33), PRIVASP (p=0.72) and P-selectin expression (p=0.37). The genotype frequencies of the 807 C/T polymorphism of the GpIa gene were similar in responders and non-responders defined by persistent HPPR (p=0.104). In conclusion, our study did not show any influence of 807 C/T polymorphism of GpIa gene on post-treatment platelet reactivity assessed by ADP-Ag, PRI VASP or P-selectin expression in 601 NSTE ACS patients.Thrombosis and Haemostasis 02/2007; 97(2):212-7. · 5.04 Impact Factor -
Article: Role of the T744C polymorphism of the P2Y12 gene on platelet response to a 600-mg loading dose of clopidogrel in 597 patients with non-ST-segment elevation acute coronary syndrome.
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ABSTRACT: Variability in platelet response to clopidogrel and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. Recently, the T744C polymorphism of the P2Y12 receptor gene has been associated with enhanced platelet aggregation in healthy volunteers, suggesting a possible mechanism for modulation of clopidogrel response. To assess whether the clopidogrel response may be influenced by the T744C P2Y12 gene polymorphism in patients with non ST elevation acute coronary syndrome (NSTE ACS). 597 NSTE ACS patients were included in our study and were divided into 3 groups: CC homozygotes, CT heterozygotes ad TT homozygotes. All patients received loading doses of 600 mg clopidogrel and 250 mg aspirin at least 12 hours before blood samples. Clopidogrel response was assessed by post-treatment ADP 10 micromol/L-induced platelet aggregation (ADP-Ag), VASP phosphorylation (PRI VASP) and P-selectin expression (PS). Clopidogrel resistance was defined by persistence of High Post-treatment Platelet Reactivity (HPPR=ADP-Ag>70%). Significant variability in the distribution of platelet parameters was observed in the overall study population. No significant difference in platelet parameter profiles was observed within patients having the same genotype, for ADP-Ag (p=0.39), PRI VASP (p=0.97) and PS (p=0.62). The genotype frequencies of the T744C polymorphism of the P2Y12 gene were similar in responders and non responders defining by HPPR (p=0.75). Our study did not show any influence of the T744C polymorphism of the P2Y12 receptor gene on clopidogrel response assessed by ADP-Ag, PRI VASP or P-selectin expression in NSTE ACS patients.Thrombosis Research 01/2007; 120(6):893-9. · 2.44 Impact Factor -
Article: Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing coronary stenting.
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ABSTRACT: We analyzed the benefit of a 600-mg clopidogrel loading dose on platelet reactivity and clinical outcomes after stenting for non-ST-segment elevation acute coronary syndrome (NSTE ACS). High post-treatment platelet reactivity (HPPR = adenosine diphosphate 10 mumol x l(-1) [ADP]-induced platelet aggregation >70%) is a marker for low responders to dual antiplatelet therapy with increased risk of recurrent cardiovascular (CV) events after stenting for NSTE ACS. A total of 292 consecutive NSTE ACS patients undergoing coronary stenting were included and randomly received a 300-mg (n = 146) or 600-mg (n = 146) loading dose of clopidogrel at least 12 h before percutaneous coronary intervention. A single post-treatment blood sample was obtained before percutaneous coronary intervention to analyze maximal intensity of ADP-induced platelet aggregation and platelet surface expression of P-selectin. One-month follow-up CV events were recorded. The ADP-induced platelet aggregation and expression of P-selectin were significantly lower in patients receiving 600 mg than in those receiving 300 mg (mean +/- SD: 50 +/- 19% vs. 61+/- 16%, p < 0.0001 and 0.38 +/- 0.24 arbitrary units vs. 0.60 +/- 0.40 arbitrary units; p < 0.0001 respectively). Persistence of HPPR was less common in patients receiving 600 mg than in those receiving 300 mg (15 vs. 25%, p = 0.03). During the 1-month follow-up, 18 CV events (12%) occurred in the 300-mg group versus 7 (5%) in the 600-mg group (p = 0.02); this difference was not affected by adjustment for conventional CV risk factors (p = 0.035). In NSTE ACS patients undergoing coronary stenting, a 600-mg loading dose of clopidogrel shows its benefit on platelet reactivity and clinical prognosis.Journal of the American College of Cardiology 10/2006; 48(7):1339-45. · 14.16 Impact Factor -
Article: Prevalence of angiographic coronary artery disease in patients hospitalized for acute diastolic heart failure without clinical and electrocardiographic evidence of myocardial ischemia on admission.
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ABSTRACT: The prevalence of coronary artery disease was investigated in 18 patients hospitalized for acute diastolic heart failure without clinical and electrocardiographic evidence of myocardial ischemia on admission. On the basis of coronary angiography, 7 patients had coronary artery disease and 4 had ischemic heart disease. In addition, besides uncontrolled hypertension and several systemic factors, silent myocardial ischemia potentially contributed to acute exacerbation of heart failure for at least 5 patients with coronary artery disease, according to either elevation in troponin I or segmental wall motion abnormalities.The American Journal of Cardiology 08/2004; 94(1):133-5. · 3.37 Impact Factor
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2007
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INSERM, GIP CYCERON
Caen, Basse-Normandie, France
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