Publications by authors named "Mathieu Pankert"

29 Publications

  • Page 1 of 1

A Thrombus on a Journey: A Massive Thrombus in Transit With Cerebral, Coronary, and Pulmonary Embolization.

Can J Cardiol 2020 Nov 16. Epub 2020 Nov 16.

Service de cardiologie, centre hospitalier nord franche comté, Trévenans, France. Electronic address:

Impending paradoxical embolism is a biatrial thrombus in transit across a patent foramen ovale. It constitutes a rare clinical condition, possibly associated with multiple embolization and high mortality. We report the exceptional case of a 71-year-old-man presenting a giant impending paradoxical thrombus, complicated with pulmonary, cerebral, and coronary embolization. The patient underwent urgent surgery and was finally discharged without complications.
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http://dx.doi.org/10.1016/j.cjca.2020.11.002DOI Listing
November 2020

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial.

Am Heart J 2020 07 30;225:19-26. Epub 2020 Apr 30.

Aix-Marseille Univ, Intensive cardiac care unit, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France; Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), Marseille, France; Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France.

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.
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http://dx.doi.org/10.1016/j.ahj.2020.04.013DOI Listing
July 2020

Optimal Timing of Intervention in NSTE-ACS Without Pre-Treatment: The EARLY Randomized Trial.

JACC Cardiovasc Interv 2020 04;13(8):907-917

Aix-Marseille Université, Intensive Care Unit, Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France; Mediterranean Association for Research and Studies in Cardiology, Marseille, France; Centre for CardioVascular and Nutrition Research, INSERM 1263, INRA 1260, Marseille, France. Electronic address:

Objectives: The aim of this study was to compare a delayed and a very early invasive strategy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) without pre-treatment.

Background: The optimal delay of the invasive strategy in patients with NSTE-ACS remains debated and has never been investigated in patients not pre-treated with P2Y-adenosine diphosphate receptor antagonists.

Methods: A prospective, open-label, randomized controlled trial was conducted. Altogether, 741 patients presenting with intermediate- or high-risk NSTE-ACS intended for an invasive strategy were included. The modified intention-to-treat analysis was composed of 709 patients after 32 withdrew consent. Patients were randomized 1:1 to the delayed invasive group (DG) (n = 363) with coronary angiography (CA) performed 12 to 72 h after randomization or the very early invasive group (EG) (n = 346) with CA within 2 h. No pre-treatment with a loading dose of a P2Y-adenosine diphosphate receptor antagonist was allowed before CA. The primary endpoint was the composite of cardiovascular death and recurrent ischemic events at 1 month, as determined by a blinded adjudication committee.

Results: Most patients had high-risk NSTE-ACS in both groups (93% in the EG vs. 92.5% in the DG). The median time between randomization and CA was 0 h (interquartile range [IQR]: 0 to 1 h) in the EG group and 18 h (IQR: 11 to 23 h) in the DG. The primary endpoint rate was significantly lower in the EG (4.4% vs. 21.3% in the DG; hazard ratio: 0.20; 95% confidence interval: 0.11 to 0.34; p < 0.001), driven by a reduction in recurrent ischemic events (19.8% vs. 2.9%; p < 0.001). No difference was observed for cardiovascular death.

Conclusions: Without pre-treatment, a very early invasive strategy was associated with a significant reduction in ischemic events at the time of percutaneous coronary intervention in patients with intermediate- and high-risk NSTE-ACS. (Early or Delayed Revascularization for Intermediate and High-Risk Non ST-Elevation Acute Coronary Syndromes; NCT02750579).
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http://dx.doi.org/10.1016/j.jcin.2020.01.231DOI Listing
April 2020

Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2019 12;74(22):2728-2739

Paris Cardiovascular Research Center, INSERM Unit 970, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Cardiology Department, Paris, France.

Background: Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access.

Objectives: This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR.

Methods: Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score-based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed.

Results: Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers.

Conclusions: n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high.
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http://dx.doi.org/10.1016/j.jacc.2019.09.054DOI Listing
December 2019

Great expectations.

Lancet 2018 01 31;391(10118):306. Epub 2018 Jan 31.

Assistance Publique-Hôpitaux de Marseille, Department of Cardiology, Hôpital Nord, Marseille, France; Mediterranean Academic Association for Research and Studies in Cardiology (MARS Cardio), Marseille, France; Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, INSERM UMRS 1076, Aix-Marseille Université, Marseille 13015, France. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(18)30096-5DOI Listing
January 2018

Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

Clin Cardiol 2018 Jan 22;41(1):5-12. Epub 2018 Jan 22.

Aix-Marseille Université, AP-HM, Unité INSERM 1076, Unité de Soins Intensifs Cardiologiques, Department of Cardiology, Hôpital Nord, Marseille, France.

According to recent literature, pretreatment with a P2Y ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y ADP receptor antagonist pretreatment.
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http://dx.doi.org/10.1002/clc.22852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490048PMC
January 2018

Initial experience with the WATCHMAN™ left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry.

Arch Cardiovasc Dis 2016 Dec 1;109(12):689-695. Epub 2016 Sep 1.

Service de cardiologie A, CHU Timone, 265, rue Saint-Pierre, Marseille cedex 05, France. Electronic address:

Background: Left atrial appendage (LAA) closure using the WATCHMAN™ device (WM) may be considered in patients with non-valvular atrial fibrillation (AF) and a high-risk of stroke who are ineligible for long-term oral anticoagulation (OAC).

Aim: To report our single-centre preliminary experience, focusing on feasibility, safety and short-term efficacy of this procedure.

Methods: Patients implanted from December 2013 to February 2014 were included. The procedure, performed under general anaesthesia, was guided by fluoroscopy and transoesophageal echocardiography (TOE). Efficacy was defined as the ability to implant the WM with no peridevice leak; safety was defined as the occurrence of in-hospital and 45-day events, including stroke, pericardial effusion and device migration.

Results: Twenty-three patients (mean age: 77.6 years; 16 men [69.6%]; mean CHADS-VASc score: 5) underwent WM implantation. The indication was gastrointestinal bleeding in 14 (60.9%) patients, cerebral haemorrhage in eight (34.8%) and need for long-term ticagrelor after stent thrombosis on clopidgrel in one (4.3%). Procedural success was 95.7% (95% confidence interval: 77.3-100.0); efficacy was 90.9% (95% confidence interval: 71.0-98.7). The size of the implanted WATCHMAN™ device was in agreement with the prespecified size, based on measurement of the LAA, in 56.5% of cases. In five cases, the criteria were not met, but the device was successfully implanted in four of these, with a good result (80.0%). Treatment at discharge was a reduced dose of anticoagulant plus aspirin in three cases (13.0%) or antiplatelet therapy alone in 20 cases (90.9%). No adverse event occurred during the index hospitalization or at 45 days. At 45 days, the LAA was sealed in 18/19 patients (94.7%) on TOE, with no difference between those who did or did not have an implanted device of the prespecified size.

Conclusion: When performed by an operator trained in the procedure, WM implantation appears to be safe and effective. This procedure may be considered in patients at high-risk of stroke who are ineligible for long-term OAC.
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http://dx.doi.org/10.1016/j.acvd.2016.03.003DOI Listing
December 2016

Chronic heart failure in heart transplant recipients: Presenting features and outcome.

Arch Cardiovasc Dis 2016 Apr 15;109(4):254-9. Epub 2016 Mar 15.

Department of cardiology, La Timone hospital, Aix-Marseille university, rue Saint-Pierre, 13385 Marseille, France.

Background: The ageing graft frequently shows coronary lesions and a restrictive physiology.

Aims: To determine the presenting features and outcome of chronic heart failure in heart transplant recipients.

Methods: In this cohort study, we compared 44 consecutive heart transplant recipients who developed chronic heart failure more than 1 year after heart transplantation with 44 control heart transplant recipients who did not develop heart failure.

Results: We found that patients who developed heart failure had more frequently a history of hypertension or diabetes before transplantation. During the 12 months after transplantation, significantly more patients had moderate-to-severe acute rejections (≥ grade 2R) in the heart failure group than in the control group. At the time of heart failure diagnosis, systolic left ventricular function was preserved in 50% of patients and coronary angiography was normal or near normal in 36% of patients. Half of the 44 patients in the heart failure group died within 2 years of heart failure diagnosis. Ascites and end-stage renal failure requiring dialysis were significantly more frequent during follow-up in the heart failure group than in the control group (respectively, 10/44 vs 0/44 [P=0.001] and 18/44 vs 5/44 [P=0.003]).

Conclusion: In heart transplant recipients presenting with heart failure, systolic left ventricular function is frequently preserved and coronary angiography is frequently abnormal, but may be normal or near normal. During follow-up, the main features of these patients are a high mortality rate after heart failure diagnosis, a frequent need for renal dialysis and frequent ascites.
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http://dx.doi.org/10.1016/j.acvd.2016.01.003DOI Listing
April 2016

Chronic kidney disease has a significant impact on platelet inhibition of new P2Y12 inhibitors.

Int J Cardiol 2015 Apr 24;184:428-430. Epub 2015 Feb 24.

Département de Cardiologie, CHU Timone, Marseille F-13385, France; INSERM, UMR1062, Nutrition, Obesity and Risk of Thrombosis, F-13385 Marseille, France; Aix-Marseille Université, Faculté de Médecine, F-13385 Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2015.02.077DOI Listing
April 2015

Body mass index has no impact on platelet inhibition induced by ticagrelor after acute coronary syndrome, conversely to prasugrel.

Int J Cardiol 2014 Oct 5;176(3):1200-2. Epub 2014 Aug 5.

Département de Cardiologie, CHU Timone, Marseille F-13385, France; Aix-Marseille Univ, INSERM UMR1062, INRA UMR1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of medicine, F-13385 Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2014.07.228DOI Listing
October 2014

Effectiveness of switching 'low responders' to prasugrel to ticagrelor after acute coronary syndrome.

Int J Cardiol 2014 Oct 4;176(3):1184-5. Epub 2014 Aug 4.

Département de Cardiologie, CHU Timone, Marseille F-13385, France; INSERM, UMR1062 - Nutrition, Obesity and Risk of Thrombosis, F-13385 Marseille, France; Aix-Marseille Université, Faculté de Médecine F-13385, Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2014.07.239DOI Listing
October 2014

Transient right internal thoracic arterial graft kink related to respiratory movements: documentation of its existence, relevance and proposed management.

Catheter Cardiovasc Interv 2014 May 9;83(6):924-8. Epub 2013 Nov 9.

Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.

In this case report, we provide the first detailed description of an intermittent mechanical kink of a right internal thoracic artery (ITA) graft to the left anterior descending coronary artery secondary to respiratory movements, and its assessment by pressure wire derived fractional flow reserve (FFR). The patient presented with recurrent unstable angina and documented anterior/anterolateral ischemia. Persistent symptoms were attributed to the ITA kink and stenting was planned on clinical grounds. However, the lesion proved not physiologically significant when FFR was assessed after intermittency related to respiratory movements was documented. Complex stenting was therefore avoided and medical therapy was prescribed for distal diagonal disease. We therefore propose that intermittency should be actively investigated when a kink is documented in a coronary bypass graft by conventional angiography (using dedicated angiographic evaluation in maximal inspiration and expiration). Furthermore, when this type of lesion is encountered, we suggest that it should be assessed physiologically using pressure wire derived FFR before potentially complex interventions are considered.
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http://dx.doi.org/10.1002/ccd.25220DOI Listing
May 2014

Unusual cause of hypoxemia in myocardial infarction: interventional management.

Int J Cardiol 2014 Apr 8;172(3):e436-7. Epub 2014 Jan 8.

Département de Cardiologie, CHU Timone, Marseille F-13385, France; Aix-Marseille Univ, INSERM UMR1062, INRA UMR1260, Nutrition, Obesity and Risk of Thrombosis, Faculty of Medicine, F-13385 Marseille, France.

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http://dx.doi.org/10.1016/j.ijcard.2013.12.177DOI Listing
April 2014

Fixed-dose aspirin-clopidogrel combination enhances compliance to aspirin after acute coronary syndrome.

Int J Cardiol 2014 Mar 8;172(1):e1-2. Epub 2014 Jan 8.

Département de Cardiologie, CHU Timone, Marseille, F-13385, France; INSERM, UMR1062, "Nutrition, Obesity and Risk of Thrombosis", F-13385, Marseille, France; Aix-Marseille Université, Faculté de Médecine, F-13385, Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2013.12.194DOI Listing
March 2014

Prasugrel versus ticagrelor in acute coronary syndrome: a randomized comparison.

Int J Cardiol 2013 Dec 14;170(2):e21-2. Epub 2013 Oct 14.

Département de Cardiologie, CHU Timone, Marseille, F-13385 France; Aix-Marseille Univ, INSERM UMR1062, INRA UMR1260, "Nutrition, Obesity and Risk of Thrombosis", Faculty of Medicine, F-13385 Marseille, France.

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http://dx.doi.org/10.1016/j.ijcard.2013.10.043DOI Listing
December 2013

Impact of obesity and the metabolic syndrome on response to clopidogrel or prasugrel and bleeding risk in patients treated after coronary stenting.

Am J Cardiol 2014 Jan 4;113(1):54-9. Epub 2013 Oct 4.

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:

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.
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http://dx.doi.org/10.1016/j.amjcard.2013.09.011DOI Listing
January 2014

Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs).

JACC Cardiovasc Interv 2013 Aug;6(8):854-63

Département de Cardiologie, CHU Timone, Marseille, France.

Objectives: This study was designed to define the hyperresponse to thienopyridine (very low on-treatment platelet reactivity [VLTPR]) as the most predictive threshold value of platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) for the prediction of non-access site-related bleeding events. We also aimed to identify predictors of bleeding and VLTPR in patients treated with thienopyridines.

Background: New P2Y12 blockers and platelet monitoring has been proposed to optimize platelet inhibition after acute coronary syndromes and improve ischemic outcomes. However, bleeding complications remain the Achilles' heel of antiplatelet therapy, and platelet monitoring could be useful to evaluate this risk.

Methods: A total of 1,542 consecutive patients undergoing coronary stenting for ACS were included in the present study (287 taking clopidogrel 75 mg, 868 taking clopidogrel 150 mg, and 387 taking prasugrel 10 mg).

Results: During 6-month follow-up, 9% of patients (n = 139) experienced nonaccess site-related Bleeding Academic Research Consortium bleeding complications. These patients were more often women and nondiabetic and had lower PRI VASP values than others (p < 0.001). Receiver-operating characteristic curve analysis (0.71, p < 0.01) identified a threshold value for VLTPR of PRI VASP ≤10% to predict bleeding events with a sensitivity of 17% and a specificity of 97%. Although prasugrel was the main predictor of VLTPR in the whole population (odds ratio: 10.2, 95% confidence interval: 3.0 to -34.2; p < 0.001), VLTPR was the strongest and independent predictor of bleeding (odds ratio: 4.7, 95% confidence interval: 2.7 to 8.3; p < 0.001).

Conclusions: The present study identified VLTPR (PRI VASP ≤10%) as the strongest predictor of bleeding complications in patients treated with thienopyridines. This marker could be useful for tailored therapy and bleeding prevention.
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http://dx.doi.org/10.1016/j.jcin.2013.04.009DOI Listing
August 2013

Effectiveness of switching 'hyper responders' from Prasugrel to Clopidogrel after acute coronary syndrome: the POBA (Predictor of Bleeding with Antiplatelet drugs) SWITCH study.

Int J Cardiol 2013 Oct 31;168(5):5004-5. Epub 2013 Jul 31.

Département de Cardiologie, CHU Timone, Marseille F-13385, France; INSERM, UMR1062, «Nutrition, Obesity and Risk of Thrombosis», F-13385 Marseille, France; Aix-Marseille Université, Faculté de Médecine, F-13385 Marseille, France.

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http://dx.doi.org/10.1016/j.ijcard.2013.07.121DOI Listing
October 2013

Off-label use of prasugrel in stable coronary artery disease is associated with greater degree of platelet inhibition compared with use after acute coronary syndrome.

Int J Cardiol 2013 Oct 30;168(3):2988-9. Epub 2013 Apr 30.

Département de Cardiologie, CHU Timone, Marseille F-13385, France; INSERM, UMR1062, "Nutrition, Obesity and Risk of Thrombosis", F-13385 Marseille, France; Aix-Marseille Université, Faculté de Médecine, F-13385 Marseille, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2013.04.052DOI Listing
October 2013

Effect of CYP2C19*2 and *17 genetic variants on platelet response to clopidogrel and prasugrel maintenance dose and relation to bleeding complications.

Am J Cardiol 2013 Apr 19;111(7):985-90. Epub 2013 Jan 19.

INSERM, UMR1062, Nutrition, Obesity and Risk of Thrombosis, Marseille, France.

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.
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http://dx.doi.org/10.1016/j.amjcard.2012.12.013DOI Listing
April 2013

Role of antiplatelet therapy in secondary prevention of acute coronary syndrome.

J Cardiovasc Transl Res 2012 Feb 6;5(1):41-51. Epub 2011 Nov 6.

Département de Cardiologie, CHU Timone, Marseille, 13385, France.

Cardiovascular disease is one of the major causes of death in developed countries, mainly related to coronary artery disease and its acute complications. Platelets play a great role in the pathogenesis of acute thrombotic events of coronary artery disease when silent chronic disease becomes acutely symptomatic. Platelet importance in coronary artery disease and pathophysiology of acute events support the large benefit of antiplatelet agents for both acute management of ACS and secondary prevention. Recent developments in oral antiplatelet therapy raised questions about the choice of the molecules, the use of single or double therapy, and the optimal dosing and duration of treatment. The present review aims to provide a current appraisal of antiplatelet therapy use after ACS and to summarize available scientific evidence for an optimal use of antiplatelet agents in daily practice, including the new P2Y12 blockers.
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http://dx.doi.org/10.1007/s12265-011-9329-4DOI Listing
February 2012

Synergy between pharmacological and mechanical reperfusion in ST-segment elevation myocardial infarction patients: 2011 update.

J Cardiovasc Med (Hagerstown) 2011 Dec;12(12):860-7

Département de Cardiologie, CHU Timone, Marseille, France.

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http://dx.doi.org/10.2459/JCM.0b013e32834da519DOI Listing
December 2011

Transradial approach and subclavian wired temporary pacemaker to increase safety of alcohol septal ablation for treatment of obstructive hypertrophic cardiomyopathy: the TRASA trial.

Arch Cardiovasc Dis 2011 Aug 27;104(8-9):444-9. Epub 2011 Aug 27.

Département de cardiologie, CHU de la Timone, Marseille, France.

Background: Alcohol septal ablation (ASA) is a therapeutic catheter-based option and an alternative to surgical myectomy in the treatment of patients with hypertrophic obstructive cardiomyopathy. Although the safety of the ASA procedure has been consistently improved, a temporary transvenous pacemaker is recommended for at least 48h postprocedure, with several drawbacks, including the risk of cardiac perforation and infection, and the absence of any fixation mechanism. In addition, femoral artery catheterization has resulted in a concomitant increase in bleedings and iatrogenic femoral artery injuries.

Aims: To evaluate and validate the feasibility of less invasive management of ASA using the transradial approach and a subclavian wired temporary pacemaker.

Methods: To avoid transfemoral temporary pacing, we used a subclavian bipolar active-fixation permanent pacing lead, stitched to the skin and connected to a desterilized recuperation pacemaker. The day before discharge, if there was no high-degree atrioventricular block, the pacemaker lead was removed. In all patients, we used the right radial access and the left main was cannulated with a 6F Judkins left 3.5 guiding catheter.

Results: Thirty consecutive patients were prospectively and successfully included in our study. No complication was observed during the hospital stay, neither access-site nor stimulation-lead related.

Conclusions: Our study shows the feasibility and safety of a transradial approach and a subclavian wired temporary pacemaker. The reduction in periprocedural complications offered by this strategy reflects the less invasive nature of ASA, without increasing the cost and complexity of the procedure.
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http://dx.doi.org/10.1016/j.acvd.2011.05.006DOI Listing
August 2011

Comparison of platelet reactivity and clopidogrel response in patients ≤ 75 Years Versus > 75 years undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome.

Am J Cardiol 2011 Nov 25;108(10):1411-6. Epub 2011 Aug 25.

Département de Cardiologie, CHU Timone, Marseille, France.

Specific data about the clopidogrel response in elderly patients are lacking. The present study was performed to compare the platelet reactivity and clopidogrel response between patients aged > 75 years and < 75 years undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome. A total of 689 patients were enrolled, including 162 patients aged > 75 years and 527 younger patients. All patients received a loading dose of 600 mg clopidogrel followed by 150 mg/day. Post-treatment platelet reactivity was assessed by adenosine diphosphate 10 μmol/L-induced platelet aggregation and the specific pharmacologic response to clopidogrel by the platelet reactivity index vasoactive stimulated phosphoprotein. High post-treatment platelet reactivity was defined as adenosine diphosphate 10 μmol/L-induced platelet aggregation >70%. Clinical events were recorded during 1 month of follow-up. The patients > 75 years old had a greater rate of both ischemic and bleeding complications (p = 0.04 and p = 0.03, respectively). The post-treatment platelet reactivity in response to both the loading and the maintenance clopidogrel dose was greater in patients > 75 years old than in the younger patients: 50 ± 17% versus 45 ± 17% (p = 0.002) and 57 ± 15% versus 53 ± 16% (p = 0.0005), respectively. The rate of high post-treatment platelet reactivity was significantly greater in patients aged > 75 years after 600 mg and 150 mg clopidogrel: 14% versus 9% (p = 0.04) and 23% versus 15% (p = 0.02), respectively. In contrast, the pharmacologic response to clopidogrel was not impaired in patients > 75 years after loading and maintenance doses: 43 ± 21% versus 46 ± 21% (p = 0.17) and 38 ± 18% versus 39 ± 18% (p = 0.55), respectively. In conclusion, patients aged > 75 years have an impaired prognosis after acute coronary syndrome. They display greater post-treatment platelet reactivity. However, this greater platelet reactivity does not seem to be related to an impaired specific response to clopidogrel.
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http://dx.doi.org/10.1016/j.amjcard.2011.06.060DOI Listing
November 2011

Usefulness of high clopidogrel maintenance dose according to CYP2C19 genotypes in clopidogrel low responders undergoing coronary stenting for non ST elevation acute coronary syndrome.

Am J Cardiol 2011 Sep 30;108(6):760-5. Epub 2011 Jul 30.

Département de Cardiologie, CHU Timone, Marseille, France.

The cytochrome P450 (CYP) 2C19*2 loss-of-function allele has been associated with impaired clopidogrel response and worse prognosis in clopidogrel-treated patients. The benefit of tailored therapy according to platelet function test results remains unclear, and the potential effect of genotypes on this benefit has not been addressed in unstable patients. The present study was designed to evaluate the benefit of tailored therapy with a higher maintenance dose according to CYP2C19 genotypes in patients identified as nonresponders who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes. Three hundred forty-six consecutive patients were enrolled and received a loading dose of 600 mg, including 86 *2 carriers (13 homozygotes and 73 heterozygotes) and 260 *2 noncarriers. Clopidogrel response, assessed with platelet reactivity index vasoactive-stimulated phosphoprotein, was significantly affected by genotype, with lower clopidogrel response in CYP2C19*2 allele carriers (p = 0.01). Accordingly, the rate of clopidogrel nonresponse was higher in CYP2C19*2 allele carriers (53% vs 41%, p = 0.04). All clopidogrel nonresponders (n = 151), including 105 *2 noncarriers and 46 *2 carriers, received high 150-mg clopidogrel maintenance doses at discharge to overcome initial low response. After 1 month, high maintenance doses overcame clopidogrel low response in only 44% of the whole population and significantly less frequently in *2 carriers than in noncarriers (28% vs 50%, p = 0.01). In conclusion, higher clopidogrel maintenance doses were able to overcome clopidogrel low response in fewer than half of clopidogrel low responders who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes. The benefit of this tailored therapy was significantly reduced in CYP2C19*2 carriers. Therefore, these patients might require alternative strategies with new P2Y₁₂ blockers.
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http://dx.doi.org/10.1016/j.amjcard.2011.05.045DOI Listing
September 2011