Publications by authors named "Luc Maillard"

28 Publications

  • Page 1 of 1

Design and rationale of a randomized trial of COBRA PzF stenting to REDUCE duration of triple therapy (COBRA-REDUCE).

Cardiovasc Revasc Med 2021 Jan 22. Epub 2021 Jan 22.

Cardiovascular Research Institute Dublin, Mater Private Hospital, Dublin, Ireland; School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons University of Medicine and Health Sciences, Dublin, Ireland. Electronic address:

Background/purpose: A coronary stent with thromboresistant and pro-healing properties such as the polymer polyzene F-coated (COBRA PzF) stent might safely allow for a very short duration of triple therapy in patients taking oral anticoagulation (OAC) who undergo coronary stenting.

Methods: The COBRA-REDUCE trial is a prospective, multinational, randomized, open-label, assessor-blinded trial. A total of 996 patients at high bleeding risk because of requirement for OAC (with a vitamin K antagonist or non-vitamin K antagonist for any indication) will be randomized at sites in the United States and Europe to treatment with the COBRA-PzF stent followed by very short duration (14 days) DAPT or a Food and Drug Administration (FDA)-approved new generation drug-eluting stent followed by guideline-recommended DAPT duration (3 or 6 months). Two co-primary endpoints will be tested at 6 months: a bleeding co-primary endpoint (bleeding academic research consortium [BARC] ≥2 bleeding beyond 14 days or after hospital discharge, whichever is later [superiority hypothesis]) and a thrombo-embolic co-primary endpoint (the composite of all-cause death, myocardial infarction, definite/probable stent thrombosis or ischaemic stroke [non-inferiority hypothesis]). The trial is registered at clinicaltrials.gov (NCT02594501).

Conclusion: The COBRA-REDUCE trial will determine whether coronary stenting with the COBRA PzF stent followed by 14 days of clopidogrel will reduce bleeding without increasing thrombo-embolic events compared with FDA-approved DES followed by 3-6 months clopidogrel in patients taking OAC and aspirin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carrev.2021.01.022DOI Listing
January 2021

Evaluation of the safety and efficacy of the Cobra PzF NanoCoated coronary stent in routine, consecutive, prospective, and high-risk patients: The e-Cobra study.

Catheter Cardiovasc Interv 2020 Jun 17. Epub 2020 Jun 17.

Center Hospitalier Annecy Genevois, Metz-Tessy, France.

Background: The Cobra PzF coronary stent is cobalt chromium with flat thin struts, nano-coated with Polyzene-F that enhance rapid reendothelialization and reduce the risk of stent thrombosis and restenosis. It is designed to overcome shortfalls of BMS and DES in patients requiring short DAPT duration.

Aims: To report procedural and 1-year clinical outcomes following Cobra PzF stent implantation in routine practice PCI.

Methods: e-Cobra registry is a multicenter prospective study to evaluate Cobra PzF stent in routine practice in patients deemed appropriate for short DAPT after PCI. The primary endpoint was MACE rate at 12 months (Cardiac death, MI, TLR). The secondary endpoint was definite stent thrombosis at 12 months.

Results: Among 940 patients (72% men, 72.8 ± 13.4 years) with multiple co-morbidities, 47% had acute coronary syndromes, and 62% were defined as high bleeding risk. A total of 1,229 lesions were treated with 1,314 stents. 36% of patients had lesion type B2 or C classification. Angiographic success was achieved in all cases. One-year follow-up was available for 97% of patients. The primary endpoint occurred in 9.0% of patients, including cardiac death 3.7%, MI 4.8%, and TLR 4.3%. Definite stent thrombosis occurred in six out of 915 (0.7%).

Conclusion: The Cobra PzF stent was safe and effective in routine practice patients and seems feasible in situations when short DAPT or Mono Antiplatelet Therapy (MAPT) is needed. One-year follow-up was associated with satisfactory clinical outcomes and validate previously reported data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.29065DOI Listing
June 2020

Toward a sequential provisional coronary bifurcation stenting technique. From kissing balloon to re-POT sequence.

Arch Cardiovasc Dis 2020 Mar 31;113(3):199-208. Epub 2020 Jan 31.

Department of Interventional Cardiology, Cardiovascular Hospital and Claude-Bernard University, INSERM Unit 1060 CARMEN, Lyon, France.

The specific anatomy of coronary bifurcations makes them prime sites of atherogenesis and complicates revascularization. Account must be taken of the systematic difference in diameter between the 3 constituent vessels so as to minimize final side-branch ostium obstruction and maintain the law of conservation of flow, while respecting the bifurcation angles. Kissing balloon inflation (KBI) was long recommended, but never clearly demonstrated clinical benefit in single-stent provisional stenting. The detrimental proximal overstretch induced by simultaneous inflation of balloons, observed clinically and confirmed experimentally, probably explains this inefficacy. Advances in knowledge of bifurcation pathophysiology and experimental bench studies gradually led to the development of a new purely sequential technique, re-POT, without balloon juxtaposition, comprising 3 successive steps: (1) initial "proximal optimization technique" (POT), (2) side-branch opening, and (3) final POT. In contrast to KBI, re-POT has been progressively assessed from bench to first clinical study. The aim of the present review is to present the pathophysiological specificities of coronary bifurcations, and some explanations for the failure of KBI which led to the development of a new purely sequential coronary bifurcation provisional stenting strategy, based on re-POT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.acvd.2019.11.003DOI Listing
March 2020

Validation of the all-comers design: Results of the TARGET-AC substudy.

Am Heart J 2020 03 27;221:148-154. Epub 2019 Nov 27.

The Lambe Institute for Translational Medicine and Curam, National University of Ireland, Galway and Saolta University Healthcare Group, Ireland. Electronic address:

Background: Results of clinical trials are often criticized by low inclusion rate and potential sampling bias in patient recruitment. The aim of this validation registry is to evaluate how far an all-comers design in the context of clinical research can ensure the representation of the true all-comers population.

Methods: This validation registry is a prospective international multicentre registry, conducted at 10 out of the total 21 centers, participating in TARGET-AC (registered under NCT02520180). During a predefined four-week period data were recorded prospectively on all PCIs performed in the participating centers, whether or not patients were enrolled in TARGET-AC. Data were collected on patient demographics, angiographic lesion- and procedural characteristics. For patients who were not enrolled in the study, operators were asked to declare the reason for not enrolling the patient, using a single-choice questionnaire.

Results: A total of 131 patients were enrolled in the TARGET-AC study during the investigated period (ER group), standing as 20% (range 4% and 54%) of all eligible cases per protocol. In the ER group more patients presented with stable angina (61% vs. 43%, respectively; P < .001). Whereas ST-elevation infarction was less common (5% vs. 26%, respectively; P < .001), there was no difference in non-ST elevation acute coronary syndrome (32% vs. 27%, respectively; P = .248). Risk factors and comorbidities did not show any difference between the ER and the non-enrolled (NER) groups, except for greater rate of significant valvular disease in the NER group (12% vs 19%, respectively; P = .037). The NER group presented more thrombotic stenoses than the ER group (20% vs 12%, respectively; P = .040). No difference was found in any other investigated angiographic parameters, like target vessels, bifurcation lesion, severe calcification or chronic total occlusions. Admission during regular working hours and availability of study nurse were associated with markedly higher recruitment rate.

Conclusion: Results suggest that TARGET AC was outbalanced for stable patients over primary PCIs as compared to real world. However in terms of risk factors and comorbidities the trial managed to represent the collective of real world clinical practice. Fairly representative cases were included at an average inclusion-to-eligible rate of 20%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2019.10.019DOI Listing
March 2020

MAPT (Mono Antiplatelet Therapy) as Regular Regimen After COBRA PzF™ NanoCoated Coronary Stent (NCS) Implantation.

Cardiovasc Revasc Med 2020 06 18;21(6):785-789. Epub 2019 Oct 18.

Service de Cardiologie, GCS ES Axium Rambot, 21, Avenue Alfred Capus, 13 090 Aix en Provence, France.

Aims: To report procedural and 1-year outcomes following COBRA PzF NCS implantation in a routine daily setting with high bleeding risk (HBR) patients treated with clopidogrel as mono antiplatelet therapy (MAPT).

Methods: This is a prospective, consecutive, observational study in HBR patients who underwent PCI with COBRA PzF NCS and treated with clopidogrel alone at discharge. The primary endpoint was definite stent thrombosis at one month. The secondary endpoint was MACE (Cardiac Death, myocardial infarction (MI), target lesion revascularization (TLR)) at 12 months.

Results: From October 2015 to December 2018, 77 patients with 120 lesions were enrolled and treated. Mean age was 78.7 ± 8.89 years, 58.5% men and 18.2% had ACS. Patients included had a minimum of 2.0 inclusion LEADERS FREE criteria. Angiographic success was achieved in all cases. The primary endpoint occurred in 0%, no stent thrombosis was occurred. MACE at 12-months (available for 52 patients) was 3.8% including cardiac death 0%, MI 0% and TLR 3.8%. No severe bleeding events (BARC3-5) or stroke or late stent thrombosis were noted.

Conclusion: Clopidogrel as MAPT after COBRA PzF NCS implantation in HBR patients is feasible and an attractive option. One-year follow-up was associated with excellent clinical outcomes and should be confirmed with large randomised study.

Condensed Abstract: This is prospective registry of high bleeding risk patients treated with the COBRA PzF NCS and MAPT at discharge. The primary end point demonstrated no stent thrombosis. The rate of major cardiac adverse events (a composite of cardiovascular death, myocardial infarction and target lesion revascularisation) at 1 year was 3.8%. No severe bleeding events, stroke or late stent thrombosis were noted. One-year follow-up was associated with good clinical outcomes and compared favorably with current devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carrev.2019.10.007DOI Listing
June 2020

Time Course of Reendothelialization with Polyzene-F Nanocoated Cobra PzF™ Coronary Stent on Rabbit Iliac Arteries.

Cardiovasc Revasc Med 2020 02 9;21(2):195-199. Epub 2019 Nov 9.

Department of Cardiology, CHRU Lille, Lille, France.

Purpose: Evaluation of reendothelialization with a new thin struts cobalt chromium alloy stent coated with a nano-layer of Polyzene™-F (PzF) in a rabbit iliac artery model.

Methods: Fifteen stented external rabbit iliac arteries were harvested at Day 7 for electron microscopy analysis following Cobra PzF stents implantation to assess reendothelialization and compare to historical data. Ten additional rabbits were used to assess time course of reendothelialization at 3 and 5 days.

Results: At Day 7, almost complete coverage of endothelial cells was observed with a coverage of 99.54 ± 0.25% of the stented area. No thrombus area was noted. At Day 3, more than half of examined pieces was reendothelialized and reached 78.30 ± 3.7% at Day 5 (p < .01 between each group). All stents were well expanded against the arterial wall and no struts were mal-apposed.

Conclusions: Reendothelialization was rapid and complete at Day 7. This is the fastest reendothelization process after stenting in this model. No stent occlusion was observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carrev.2019.11.005DOI Listing
February 2020

Prospective evaluation of drug eluting self-apposing stent for the treatment of unprotected left main coronary artery disease: 1-year results of the TRUNC study.

Catheter Cardiovasc Interv 2020 08 6;96(2):E142-E148. Epub 2019 Nov 6.

Barts Heart Centre, London, UK.

Objectives: To assess long-term safety and efficacy of the Xposition S self-apposing stent in the treatment of unprotected left main coronary artery (ULMCA) disease.

Background: Percutaneous intervention with stents has emerged as a valid alternative to surgical revascularization to treat ULMCA disease. Conventional balloon-expandable stents face technical challenges, particularly in large left main diameter requiring extensive optimization and side branch access in distal bifurcation. Xposition S allows for optimal apposition, bridging diameter differences, and allows expansion to vessel diameters up to 6.0 mm.

Methods: Between June 2016 and July 2017, 205 patients were enrolled in this international, prospective, multicenter registry. Patients with SYNTAX score ≥ 33 or recent STEMI were excluded. IVUS during procedure was performed in a prespecified subgroup of 50 patients. The primary clinical endpoint was 12 months Target lesion failure (TLF) and the primary efficacy endpoint was angiographic success.

Results: Distal left main bifurcation was involved in 92.7%, treated with provisional approach in most cases (79.4%). TLF rate at 12 months was 8.3%, which was defined as a composite of cardiac death (2.0%), target-vessel MI (2.9%), and TLR (5.4%). Most revascularizations occurred at SB ostium. IVUS analysis demonstrated optimal stent apposition with only one reported malapposition and promising poststenting minimal stent area measures.

Conclusions: The TRUNC study confirms that Xposition S self-apposing stent is a valid and feasible option for the treatment of ULMCA disease. Such results were reached without the systematic need of stent optimisation techniques, focusing mainly on lesion treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.28584DOI Listing
August 2020

Association of Sex With Outcomes in Patients Undergoing Percutaneous Coronary Intervention: A Subgroup Analysis of the GLOBAL LEADERS Randomized Clinical Trial.

JAMA Cardiol 2020 01;5(1):21-29

National Heart and Lung Institute, Imperial College London, London, England.

Importance: Women experience worse ischemic and bleeding outcomes after percutaneous coronary intervention (PCI).

Objectives: To assess the association of sex with patient outcomes at 2 years after contemporary PCI and with the efficacy and safety of 2 antiplatelet strategies.

Design, Setting, And Participants: This study is a prespecified subgroup analysis of the investigator-initiated, prospective, randomized GLOBAL LEADERS study evaluating 2 strategies of antiplatelet therapy after PCI in an unselected population including 130 secondary/tertiary care hospitals in different countries. The main study enrolled 15 991 unselected patients undergoing PCI between July 2013 and November 2015. Patients had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure. Data were analyzed between January 1, 2019, and March 31, 2019.

Interventions: Eligible patients were randomized to either the experimental or reference antiplatelet strategy. Experimental strategy consisted of 1 month of dual antiplatelet therapy (DAPT) followed by 23 months of ticagrelor monotherapy, while the reference strategy comprised of 12 months of DAPT followed by 12 months of aspirin monotherapy.

Main Outcomes And Measures: The primary efficacy end point was the composite of all-cause mortality and new Q-wave myocardial infarction at 2 years. The secondary safety end point was Bleeding Academic Research Consortium type 3 or 5 bleeding.

Results: Of the 15 968 patients included in this study, 3714 (23.3%) were women. The risk of the primary end point at 2 years was similar between women and men (adjusted hazard ratio [HR], 1.00; 95% CI, 0.83-1.20). Compared with men, women had higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (adjusted HR, 1.32; 95% CI, 1.04-1.67) and hemorrhagic stroke at 2 years (adjusted HR, 4.76; 95% CI, 1.92-11.81). At 2 years, there was no between-sex difference in the efficacy and safety of the 2 antiplatelet strategies. At 1 year, compared with DAPT, ticagrelor monotherapy was associated with a lower risk of bleeding in men (HR, 0.72; 95% CI, 0.53-0.98) but not in women (HR, 1.23; 95% CI, 0.80-1.89; P for interaction = .045).

Conclusions And Relevance: Compared with men, women experienced a higher risk of bleeding and hemorrhagic stroke after PCI. The effect of 2 antiplatelet strategies on death and Q-wave myocardial infarction following PCI did not differ between the sexes at 2 years.

Trial Registration: ClinicalTrials.gov identifier: NCT01813435.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2019.4296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029729PMC
January 2020

Sequential coronary bifurcation revascularization with the Xposition S™ self-apposing stent: a comparative fractal bench study.

Heart Vessels 2020 Jan 27;35(1):132-135. Epub 2019 Jun 27.

Cardiology Department, Cardiovascular Hospital and INSERM U-1060, Lyon, France.

Coronary bifurcation revascularization needs to take account of the diameter differential between vessels and to limit side-branch obstruction (SBO). The self-apposing properties of the Xposition S™ stent (STENTYS, France) seem interesting in this regard. The present experimental fractal bench study determined the best provisional stenting technique using Xposition S™. Three sequential strategies were compared (n = 5/group): implantation alone, side-branch inflation (SBI), and re-POT (initial proximal optimization technique (POT) + SBI + final POT). 2D- and 3D-OCT analyses and micro-CT scan were performed to quantify the main mechanical results at each step. Of the three groups, SBI and re-POT provided better final results than implantation alone in terms of residual SBO (respectively, 24.6 ± 5.6% and 24.8 ± 5.0% vs. 46.5 ± 10.3%, p < 0.05) and malapposition (respectively, 0.9 ± 0.6% and 0.8 ± 0.4% vs. 3.8 ± 1.9%, p < 0.05). Unlike SBI, the two POTs of the re-POT sequence did not improve the final result. SBI, alone or as part of re-POT, systematically led to one connector breakage, whereas implantation alone maintained complete stent integrity (p < 0.05). In Xposition S™ implantation, SBI should be systematic, but not post-dilatation specifically dedicated to bifurcation stenting (i.e., POTs). However, global post-dilatation is still mandatory to prevent stent underexpansion due to untreated stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00380-019-01460-8DOI Listing
January 2020

2-Year Clinical Outcomes of an Abluminal Groove-Filled Biodegradable-Polymer Sirolimus-Eluting Stent Compared With a Durable-Polymer Everolimus-Eluting Stent.

JACC Cardiovasc Interv 2019 09 22;12(17):1679-1687. Epub 2019 May 22.

The Lambe Institute for Translational Medicine and Curam, National University of Ireland, Galway, and Saolta University Healthcare Group, University College Hospital Galway, Galway, Ireland.

Objectives: The aim of this study was to assess the 2-year clinical outcomes of the Firehawk stent (Shanghai MicroPort Medical Group, Shanghai, China), a novel abluminal groove-filled biodegradable-polymer sirolimus-eluting coronary stent, compared with XIENCE (Abbott Vascular, Santa Clara, California), a durable-polymer everolimus-eluting coronary stent.

Background: The long-term outcomes of the Firehawk stent have not been evaluated beyond 1 year in a randomized all-comers clinical trial.

Methods: The TARGET All Comers study is a prospective, multicenter, all-comers, randomized, noninferiority trial conducted in Europe. A total of 1,653 patients were randomly assigned to undergo implantation of either the Firehawk or the XIENCE stent. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Results: At 2-year follow-up, the incidence of target lesion failure was 8.7% in the Firehawk group versus 8.6% in the XIENCE group (p = 0.92). The event rates of individual components of the primary endpoint were comparable for the 2 groups. Landmark analyses between 1- and 2-year follow-up revealed no statistically significant difference of TLF for the Firehawk versus the XIENCE stent. Beyond 1 year, very late definite or probable stent thrombosis occurred in 3 patients (0.4%) in the Firehawk group and in 7 patients (0.9%) in the XIENCE group (p = 0.34).

Conclusions: The 2-year follow-up of the TARGET All Comers study confirms comparable safety and efficacy profiles of the Firehawk and XIENCE stents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcin.2019.05.001DOI Listing
September 2019

Percutaneous coronary interventions with the Absorb Bioresorbable vascular scaffold in real life: 1-year results from the FRANCE ABSORB registry.

Arch Cardiovasc Dis 2019 Feb 7;112(2):113-123. Epub 2019 Jan 7.

Service de cardiologie et maladies vasculaires, CIC-IT 804, hôpital Pontchaillou, CHU de Rennes, 35033 Rennes, France; Inserm U1099, laboratoire de traitement du signal et de l'image, université de Rennes 1, 35000 Rennes, France.

Background: Several randomized studies have shown that bioresorbable vascular scaffold (BVS) technology is associated with an increased risk of stent thrombosis.

Aim: This study aimed to assess the rates of adverse outcomes at 1 year in patients treated with the Absorb BVS (Abbott Vascular, Santa Clara, CA, USA), using data from a large nationwide prospective multicentre registry (FRANCE ABSORB).

Methods: All patients receiving the Absorb BVS in France were included prospectively in the study. Predilatation, optimal sizing and postdilatation were recommended systematically. The primary endpoint was a composite of cardiovascular death, myocardial infarction and target lesion revascularization at 1 year. Secondary endpoints were scaffold thrombosis and target vessel revascularization at 1 year.

Results: A total of 2072 patients at 86 centres were included: mean age 55±11 years; 80% men. The indication was acute coronary syndrome (ACS) in 49% of cases. Predilatation and postdilatation were done in 93% and 83% of lesions, respectively. At 1 year, the primary endpoint occurred in 3.9% of patients, the rate of scaffold thrombosis was 1.5% and the rate of target vessel revascularization was 3.3%. In a multivariable analysis, diabetes and total Absorb BVS length>30mm were independently associated with the occurrence of the primary endpoint, whereas oral anticoagulation and total Absorb BVS length>30mm were independently associated with occurrence of scaffold thrombosis.

Conclusions: The Absorb BVS was implanted in a relatively young population, half of whom had ACS. Predilatation and postdilatation rates were high, and 1-year outcomes were acceptable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.acvd.2018.09.007DOI Listing
February 2019

Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable polymer coronary stent (TARGET All Comers): a multicentre, open-label, randomised non-inferiority trial.

Lancet 2018 09 3;392(10153):1117-1126. Epub 2018 Sep 3.

Yale University School of Medicine, New Haven, CT, USA; Barts Heart Centre, London and Queen Mary University of London, London, UK.

Background: The FIREHAWK is a drug-eluting stent with a fully biodegradable sirolimus-containing polymer coating localised to recessed abluminal grooves on the stent surface. We investigated clinical outcomes with this targeted, low-dose, biodegradable polymer, sirolimus-eluting stent compared with XIENCE durable polymer, everolimus-eluting stents in an all-comers population.

Methods: The TARGET All Comers study was a prospective, multicentre, open-label randomised non-inferiority trial done at 21 centres in ten European countries. Patients with symptomatic or asymptomatic coronary artery disease and objective evidence of myocardial ischaemia who qualified for percutaneous coronary intervention were randomised 1:1 to undergo implantation of a FIREHAWK or XIENCE. Randomisation was web-based, with random block allocation and stratification by centre and ST elevation myocardial infarction. Outcome assessors were masked to treatment allocation, but treating physicians and patients were not. The primary endpoint was target lesion failure at 12 months, a composite of cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation. The control event rate for XIENCE was assumed to be 7%, the non-inferiority margin was 3.5%, and the primary analysis was in the intention-to-treat population, censoring patients who did not have either an event before 365 days or contact beyond 365 days. Late lumen loss was the primary endpoint of an angiographic substudy designed to investigate the non-inferiority of the FIREHAWK compared with the XIENCE stent. This trial is registered with ClinicalTrials.gov, number NCT02520180.

Findings: From Dec 17, 2015, to Oct 14, 2016, 1653 patients were randomly assigned to implantation of the FIREHAWK (n=823) or XIENCE (n=830). 65 patients in the FIREHAWK group and 66 in the XIENCE group had insufficient follow-up data and were excluded from the analyses. At 12 months, target lesion failure occurred in 46 (6·1%) of 758 patients in the FIREHAWK group and in 45 (5·9%) of 764 patients in the XIENCE group (difference 0·2%, 90% CI -1·9 to 2·2, p=0·004, 95% CI -2·2 to 2·6, p=0·88). There were no differences in ischaemia-driven revascularisation or stent thrombosis rates at 12 months. 176 patients were included in the angiographic substudy, in which in-stent late lumen loss was 0·17 mm (SD 0·48) in the FIREHAWK group and 0·11 mm (0·52) in the XIENCE group (p=0·48), with an absolute difference of 0·05 mm (95% CI -0·09 to 0·18, p=0·024).

Interpretation: In a broad all-comers population of patients requiring stent implantation for myocardial ischaemia, the FIREHAWK was non-inferior to the XIENCE as assessed with the primary endpoint of target lesion failure at 12 months and in-stent late lumen loss at 13 months. The FIREHAWK is a safe and effective alternative stent to treat patients with ischaemic coronary artery disease in clinical practice.

Funding: Shanghai Microport Medical.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(18)31649-0DOI Listing
September 2018

Polymer-free drug-coated coronary stents in diabetic patients at high bleeding risk: a pre-specified sub-study of the LEADERS FREE trial.

Clin Res Cardiol 2019 Jan 27;108(1):31-38. Epub 2018 Jun 27.

Hopital LaTour, Geneva, Switzerland.

Objective: Diabetics are at increased risk after stent implantation and potentially sensitive to the type of stent and dual anti-platelet therapy (DAPT). The randomized, double-blind LEADERS FREE trial compared 2432 patients at high bleeding risk (HBR) receiving either a polymer-free BA9-coated stent (DCS) or a bare metal stent (BMS) with 1 month of DAPT, and showed superior safety and efficacy of the DCS at 2 years. We report outcomes at 2 years of the pre-specified diabetic subgroup.

Methods And Results: The diabetic sub-group comprised 805 (33.1%) patients; 262 (10.8%) were insulin-dependent (IDDM). Compared to non-diabetics, diabetics were younger and had more risk factors and multi-vessel disease. They suffered higher rates of death (15.6 vs. 12.2%, p = 0.01), cardiac death (8.3 vs. 5.9%, p = 0.02), myocardial infarction (MI) (11.1 vs. 7.8%, p = 0.009) and definite/probable stent thrombosis (3.1 vs. 1.7%, p = 0.01), but rates of clinically-indicated TLR (9.1 vs. 9.5%, p = 0.93) and BARC 3-5 bleeding (10.2 vs. 8.4%, p = 0.20) were comparable. Compared to diabetic patients treated with a BMS, diabetic DCS recipients required less clinically driven TLR (6.3 vs. 12.2%, p = 0.006). The primary safety endpoint (cardiac death, MI, definite/probable stent thrombosis) occurred numerically less frequently in the DCS group (14.9 vs. 19.7%, p = 0.10), and was significantly lower in IDDM patients (13.8 vs. 25.4%, p = 0.03). BARC 3-5 was similar for patients treated with DCS (9.9%) and BMS (10.5%, p = 0.84).

Conclusions: In diabetic HBR patients, DCS significantly reduced re-intervention rates over BMS, and showed a strong trend towards a safety benefit at 2 years.

Clinical Trial Registration: ClinicalTrials.gov number: NCT01623180.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00392-018-1308-1DOI Listing
January 2019

Benefit of a new provisional stenting strategy, the re-proximal optimisation technique: the rePOT clinical study.

EuroIntervention 2018 06 8;14(3):e325-e332. Epub 2018 Jun 8.

Department of Interventional Cardiology, Cardiovascular Hospital and Claude Bernard University and INSERM Unit 1060 CARMEN, Lyon, France.

Aims: A new coronary bifurcation provisional stenting technique without kissing balloon, rePOT, associating the proximal optimisation technique (POT), side branch inflation and final POT, showed excellent mechanical results in a bench test. The present study sought to use optical coherence tomography (OCT) to quantify the mechanical results of rePOT in vivo in a large patient sample with complex coronary bifurcations.

Methods And Results: A total of 106 patients with coronary bifurcations were included in a multicentre prospective registry (left main, 40.6%; true Medina bifurcation, 39.6%). Three OCT runs were performed, at baseline, just after stent implantation and after the complete rePOT sequence, quantifying global malapposition, side branch obstruction (SBO), and various geometric arterial criteria. RePOT was completed systematically. RePOT significantly reduced global strut malapposition from 18.9±13.4% just after stent implantation to 3.2±3.9% (p<0.05), residual SBO from 44.3±12.9% to 17.0±14.3% (p<0.05), and ellipticity index from 1.19±0.11 to 1.13±0.12 (p<0.05). Exhaustive six-month follow-up found only one mother-vessel target lesion revascularisation.

Conclusions: This clinical study of a large sample of complex coronary bifurcations with OCT analysis showed the benefit of the rePOT sequence in provisional stenting, replicating in vivo the excellent in vitro geometric results previously reported, and confirming ease of implementation and medium-term safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4244/EIJ-D-17-00941DOI Listing
June 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.22852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490048PMC
January 2018

Immediate and 1-year follow-up with the novel nanosurface modified COBRA PzF stent.

Arch Cardiovasc Dis 2017 Dec 6;110(12):682-688. Epub 2017 Nov 6.

Department of cardiology, GCS ES-Axium-Rambot, 21, avenue Alfred-Capus, 13090 Aix-en-Provence, France.

Background: The COBRA PzF coronary stent, which has a unique nano-coating of Polyzene-F, was developed to reduce the risk of stent thrombosis.

Aims: To report procedural and 1-year clinical outcomes following COBRA PzF coronary stent implantation in a real-world percutaneous coronary intervention (PCI) registry.

Methods: All patients assigned to treatment with the COBRA PzF in the GCS Axium Rambot Center, Aix-en-Provence, France between February 2013 to June 2014 were prospectively enrolled.

Results: Among 100 patients (71% men, mean±standard error age 71.4±11.0 years), 38% had acute coronary syndromes. The population was consistent with real-world experience and included patients with multiple co-morbidities and 26% with diffuse multivessel disease. A total of 151 lesions were treated with 166 stents, including 26% of lesions with a type B2 or C classification. Pre- and post-procedural quantitative coronary angiography analyses showed a mean acute gain of 2.2±0.2mm. Angiographic success was achieved in all cases. One-year follow-up was available for all patients and the target vessel failure (composite of all-cause mortality, myocardial infarction or target vessel revascularization) rate was 12%, including 2% mortality (end-stage cardiomyopathy), 5% myocardial infarction (five periprocedural myocardial infarctions with isolated troponin elevation without chest pain or Q waves) and 5% target lesion revascularization. There were no cases of definite stent thrombosis.

Conclusion: The COBRA PzF stent was safe and effective in routine practice. One-year follow-up was associated with excellent clinical outcomes and compared favourably with current devices. These results are very promising in a real-world population of complex patients, and further study is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.acvd.2017.04.010DOI Listing
December 2017

Safety and Efficacy of Polymer-Free Biolimus A9-Coated Versus Bare-Metal Stents in Orally Anticoagulated Patients: 2-Year Results of the LEADERS FREE Oral Anticoagulation Substudy.

JACC Cardiovasc Interv 2017 08;10(16):1633-1642

Hôpital La Tour, Meyrin, Switzerland.

Objectives: The aim of this study was to compare the performance of drug-coated stents (DCS) versus bare-metal stents (BMS) in patients who are candidates for long-term oral anticoagulation (OAC) after percutaneous coronary interventions.

Background: The randomized controlled LEADERS FREE (A Randomized Clinical Evaluation of the BioFreedom™ Stent) trial demonstrated the superior safety and efficacy of a polymer-free biolimus A9 DCS compared with a similar BMS used with 1 month of dual antiplatelet therapy in 2,466 patients at high bleeding risk.

Methods: The 2 stents were compared in a pre-specified analysis of the 879 LEADERS FREE patients (35.6%) scheduled to remain on OAC after percutaneous coronary intervention. The primary safety endpoint was a composite of cardiac death, myocardial infarction, and stent thrombosis. The primary efficacy endpoint was the incidence of clinically driven target lesion revascularization.

Results: Baseline characteristics of 448 DCS and 431 BMS recipients were similar, 78.8% had histories of atrial fibrillation, and 21% presented with acute coronary syndromes. Four hundred patients in the DCS group and 376 in the BMS group were discharged on OAC after percutaneous coronary intervention. At 2 years, for the DCS and BMS recipients, respectively, the incidence of clinically driven target lesion revascularization was 7.5% versus 11.2% (hazard ratio: 0.63; 95% confidence interval: 0.40 to 1.01; p = 0.0514), the safety endpoint was reached by 14.4% and 15.0% (p = NS), and the rates of major bleeding events (Bleeding Academic Research Consortium 3 to 5) were 10.7% and 12.9% (p = NS).

Conclusions: The efficacy advantage of DCS over BMS up to 2 years appears confirmed in patients on long-term OAC. Despite the very short course of dual antiplatelet therapy, both the DCS and BMS groups experienced similarly high rates of major bleeding. (A Randomized Clinical Evaluation of the BioFreedom™ Stent [Leaders Free]; NCT01623180).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcin.2017.05.033DOI Listing
August 2017

6- Versus 24-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents in Patients Nonresistant to Aspirin: Final Results of the ITALIC Trial (Is There a Life for DES After Discontinuation of Clopidogrel).

JACC Cardiovasc Interv 2017 06;10(12):1202-1210

Department of Cardiology Brest University, Brest, France. Electronic address:

Objectives: The aim of this study was to test the hypothesis that 6-month dual antiplatelet therapy (DAPT) is noninferior to 24-month DAPT in aspirin-sensitive patients.

Background: The ITALIC (Is There a Life for DES After Discontinuation of Clopidogrel) trial showed that rates of bleeding and thrombotic events at 1 year were much the same with 6 versus 12 months of DAPT after percutaneous coronary intervention with second-generation drug-eluting stents. In this report, 2-year follow-up is presented.

Methods: In a multicenter randomized study, patients with confirmed nonresistance to aspirin undergoing drug-eluting stent implantation were allocated to 6 or 24 months of DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-percutaneous coronary intervention. The secondary endpoints comprised the same composite endpoint at 24 months and each individual component.

Results: Overall, 2,031 patients from 70 centers were screened; 926 were randomized to 6-month and 924 to 24-month DAPT. Noninferiority was demonstrated for 6- versus 12-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p = 0.0002). At 2 years, the composite endpoint was unchanged, at 3.5% for 6 months and 3.7% for 24 months (p = 0.79), and rates of myocardial infarction (1.3% vs. 1.0%; p = 0.51), stroke (0.6% vs. 0.8%; p = 0.77), and target vessel revascularization (1.0% vs. 0.3%; p = 0.09) were likewise similar. There was a trend toward higher mortality with longer DAPT (2.2% vs. 1.2%; p = 0.11). Four patients (0.4%) in the 24-month group and none in the 6-month group had major bleeding.

Conclusions: Two-year outcomes in the ITALIC trial confirmed the 1-year results and showed that patients receiving 6-month DAPT after percutaneous coronary intervention with second-generation drug-eluting stent have similar outcomes to those receiving 24-month DAPT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcin.2017.03.049DOI Listing
June 2017

Safety and efficacy outcomes of 3rd generation DES in an all-comer population of patients undergoing PCI: 12-month and 24-month results of the e-Biomatrix French registry.

Catheter Cardiovasc Interv 2017 Nov 22;90(6):890-897. Epub 2017 May 22.

Ramsay Générale de Santé, Institut Cardiovasculaire Paris Sud, Massy, France.

Objectives: The French Ebiomatrix registry aimed to confirm the results of the Leaders trial in an all-comer population in France.

Background: The Leaders trial showed the Biolimus-eluting-sent (BES) to be equivalent to the Cypher stent in terms of safety and efficacy at 1 year and superior regarding stent thrombosis after 1 year.

Methods: BES recipients were enrolled in 42 French centers with up to 24-month clinical follow up.

Results: 2365 patients were included. Mean age: 65.7 ±11.2 years, 76.1% males, 31.8% had diabetes, 36.5% ACS (28.7% non-ST-elevation MI and 7.8% with ST-elevation MI). 1.7 ± 1.0 stents/patient were implanted and procedural success was 99.5%. 12-month follow-up was completed in 94.3% patients and 24 months in 91.4%. MACCE rates at 12 and 24 months were 5.8% and 9% (all cause-death 1.5% and 2.2%; stent thrombosis definite/probable 0.4% and 0.6%), respectively. MACCE were not significantly higher in diabetic patients compared with non-diabetics but cardiac death was higher (1.6% vs. 0.6%, P = 0.01 at 1 year and 1.9% vs. 0.6, P = 0.005 at 2 years) as was stent thrombosis (0.9% vs. 0.2%, P = 0.009 and 1.2 vs. 0.3% P = 0.008). Compared with non-ACS patients, MACCE was significantly higher in the ACS subgroup (7.5% vs. 4.8%, P = 0.001 at 1 year and 10.3% vs.8.1%, P = 0.07 at 2 years).

Conclusion: In this large real-world registry, the BES with biodegradable polymer showed excellent acute and mid-term outcomes with a 5.8% and 9% rate of MACCE at one and 2 years and a very low rate of stent thrombosis between 1 and 2 years (0.2%), thus demonstrating the replicability of the LEADERS trial in a registry population. © 2017 The Authors Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.27081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724651PMC
November 2017

9-Month Clinical and Angiographic Outcomes of the COBRA Polyzene-F NanoCoated Coronary Stent System.

JACC Cardiovasc Interv 2017 01;10(2):160-167

CeloNova BioSciences, San Antonio, Texas.

Objectives: The aim of this study was to assess the safety and effectiveness of the COBRA Polyzene-F NanoCoated Coronary Stent System (CeloNova Biosciences, San Antonio, Texas) for the treatment of de novo coronary artery lesions.

Background: Polyzene-F-coated coronary stents have shown reduced thrombogenicity and inflammation in preclinical studies.

Methods: Patients with de novo coronary artery lesions meeting eligibility criteria were enrolled in a nonrandomized, prospective clinical trial. The primary endpoint was target vessel failure (TVF) (defined as a composite of cardiac death, myocardial infarction, or clinically driven target vessel revascularization) at 9 months. A pre-specified subset was planned for routine repeat angiographic follow-up at 9 months. The powered secondary endpoint was mean late lumen loss (LL). The comparator was a performance goal derived from meta-analysis of historical bare-metal stent trials of 19.62% for TVF and 1.1 mm for LL. Other secondary endpoints were clinically driven target lesion revascularization and definite or probable stent thrombosis.

Results: Of 296 enrolled patients, 287 (97%) completed primary endpoint analysis; 130 were planned for angiographic follow-up and 115 (88%) completed. At 9 months, TVF had occurred in 33 patients (11.5%; upper 95% confidence boundary: 15.07%), including 1 (0.3%) cardiac death, 20 (7.0%) myocardial infarctions (17 periprocedural), and 17 (5.9%) target vessel revascularizations. LL was 0.84 ± 0.48 mm (upper 95% confidence boundary: 0.92). Target lesion revascularization occurred in 13 patients (4.6%). There were no stent thrombosis events.

Conclusions: The COBRA Polyzene-F stent met performance goals for TVF and LL at 9 months. There was an excellent safety profile, with infrequent late myocardial infarction and no stent thrombosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcin.2016.10.037DOI Listing
January 2017

2-Year Outcomes of High Bleeding Risk Patients After Polymer-Free Drug-Coated Stents.

J Am Coll Cardiol 2017 Jan 30;69(2):162-171. Epub 2016 Oct 30.

Cardiovascular Department, Hôpital de la Tour, Geneva, Switzerland. Electronic address:

Background: A 1-year follow-up, polymer-free metallic stent coated with biolimus-A9 followed by 1-month dual antiplatelet therapy is safer and more effective than a bare-metal stent (BMS) for patients with high risk of bleeding.

Objectives: This study analyzed 2-year outcomes to determine whether these benefits are maintained.

Methods: In a prospective, multicenter, double-blind trial, we randomized 2,466 high bleeding risk patients to receive a drug-coated stent (DCS) or a BMS followed by 1-month dual antiplatelet therapy. The primary safety endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy endpoint was clinically driven target lesion revascularization.

Results: At 2 years, the primary safety endpoint had occurred in 147 DCS and 180 BMS patients (15.3%) (hazard ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.039). Clinically driven target lesion revascularization occurred for 77 DCS and 136 BMS patients (12.0%) (hazard ratio: 0.54; 95% confidence interval: 0.41 to 0.72; p < 0.0001). Major bleeding occurred in 8.9% of DCS and 9.2% of BMS patients (p = 0.95), and a coronary thrombotic event (myocardial infarction and/or stent thrombosis) occurred in 8.2% of DCS and 10.6% of BMS patients (p = 0.045). One-year mortality was 27.1% for a major bleed and 26.3% for a thrombotic event. At 2 years, multivariate correlates of major bleeding were age >75 years, anemia, raised plasma creatinine, and planned long-term anticoagulation. Correlates of the primary safety endpoint were age, anemia, congestive heart failure, multivessel disease, number of stents implanted, and use of a BMS rather than a DCS.

Conclusions: Safety and efficacy benefits of DCS over BMS were maintained for 2 years in high bleeding risk patients. Rates of major bleeding and coronary thrombotic events were no different and were associated with a substantial and comparable mortality risk. (A Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug Coated Stent Versus the Gazelle Bare Metal Stent in Patients With High Risk of Bleeding [LEADERS FREE]; NCT01623180).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2016.10.009DOI Listing
January 2017

Preclinical evaluation of a novel polyphosphazene surface modified stent.

Int J Cardiol 2016 Nov 30;222:217-225. Epub 2016 Jul 30.

CVPath Institute, Inc., Gaithersburg, MD, United States.

Background: Treatment options for patients with coronary artery disease at high risk for bleeding complications are limited. The aim of the current preclinical study was to evaluate neointimal coverage, endothelial recovery, inflammation and thrombogenicity in a novel thin-strut (71μm thickness) Cobalt Chromium (CoCr) stent modified with a nano-thin Polyzene®-F (PzF) surface coating.

Methods And Results: Twenty-eight single PzF nano-coated stents and 20 bare metal control stents (BMS) were implanted in the coronary arteries of 24 pigs, with scheduled 5- (n=5), 28- (n=13), and 90-day (n=6) follow-up in addition to overlapping configuration (n=6 each), examined at 28-days. Histomorphometric analysis showed significantly lower neointimal thickness in PzF nano-coated stents than BMS controls at both 28- and 90-days (p=0.023 and 0.005) and reduced inflammation (p=0.06 and 0.13). Endothelial coverage over luminal surfaces at all time points was similar between nano-coated stents and BMS controls. We conducted supplementary in-vitro experiments using human monocytes and an ex-vivo swine carotid-jugular arterio-venous shunt model to better understand the healing properties afforded by the PzF nano-coating. Overall, the PzF-nano-coating showed reduced monocyte adhesion and thrombus formation compared to the un-coated controls.

Conclusions: Stents modified with a nano-thin PzF-coating implanted in healthy swine indicate favorable vascular healing properties shown by reduced neointimal hyperplasia and inflammation, along with resistance to thrombus formation in an ex-vivo shunt model over unmodified stents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2016.07.181DOI Listing
November 2016

6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: the randomized, multicenter ITALIC trial.

J Am Coll Cardiol 2015 Mar 16;65(8):777-786. Epub 2014 Nov 16.

Générale de Santé, Institut Cardiovasculaire Paris Sud, Massy, France.

Background: The currently recommended duration of dual antiplatelet therapy (DAPT) in drug-eluting stent (DES) recipients is 12 months to reduce the risk of late stent thrombosis, particularly in those with acute coronary syndrome (ACS).

Objectives: This study hypothesized that antiplatelet treatment with DAPT for 6 months may be noninferior to 24-month DAPT in aspirin-sensitive patients.

Methods: A multicenter, randomized study assigned patients undergoing implantation of everolimus-eluting stents with confirmed nonresistance to aspirin to receive 6- or 24-month DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-stenting.

Results: A total of 2,031 patients were enrolled in 70 European and Middle Eastern centers. The trial was prematurely terminated due to recruitment problems, leaving 941 patients randomized to 24-month DAPT and 953 to 6-month DAPT. The 2 treatment groups had similar baseline and procedural characteristics. There was no significant difference in the primary endpoint (24-month: 1.5% vs. 6-month: 1.6%; p = 0.85). Noninferiority was demonstrated for 6- versus 24-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p for noninferiority = 0.0002). There were no significant differences in stent thrombosis or bleeding complications. In the 792 (44%) high-risk patients with ACS, primary and secondary endpoints did not significantly differ (hazard ratio: 1.7 [95% confidence interval: 0.519 to 6.057; p = 0.361]).

Conclusions: Rates of bleeding and thrombotic events were not significantly different according to 6- versus 24-month DAPT after PCI with new-generation DES in good aspirin responders. (Is There A LIfe for DES After Discontinuation of Clopidogrel [ITALICplus]; NCT01476020).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2014.11.008DOI Listing
March 2015

Effect of ticagrelor-related dyspnea on compliance with therapy in acute coronary syndrome patients.

Int J Cardiol 2014 Apr 22;173(1):120-1. Epub 2014 Feb 22.

Département de Cardiologie Centre Hospitalo-Universitaire Nord, Aix-Marseille Univ., Marseille, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2014.02.028DOI Listing
April 2014

A randomized trial of platelet reactivity monitoring-adjusted clopidogrel therapy versus prasugrel therapy to reduce high on-treatment platelet reactivity.

Int J Cardiol 2013 Oct 2;168(4):4244-8. Epub 2013 Aug 2.

Département de cardiologie, Hôpital universitaire nord, Aix-Marseille Univ., Marseille, France; INSERM UMRS 608, UFR de pharmacie, Marseille, France. Electronic address:

Background: Peri-procedural platelet reactivity (PR) inhibition is critical in patients undergoing percutaneous coronary intervention (PCI). High on-treatment PR (HTPR) was associated with recurrent ischemic events in acute coronary syndrome (ACS) patients undergoing PCI. We aimed to compare a strategy of clopidogrel loading dose-adjustment (CDA) according to PR monitoring with standard prasugrel therapy to reduce the rate of patients exhibiting HTPR.

Methods: We enrolled 177 ACS patients in a prospective multicentre randomized trial comparing CDA according to PR monitoring and prasugrel therapy. The VASP index was used to measure PR and a VASP ≥ 50% defined HTPR. The primary endpoint of the study was the rate of HTPR on discharge.

Results: Baseline characteristics of the CDA group (n = 88) and of the prasugrel group (n = 89) were similar. CDA significantly reduced PR and the rate of HTPR compared to a single LD of clopidogrel (30.9 ± 13.9%; p < 0.0001 and 43 to 2.3%; p < 0.001, respectively). Following CDA the rate of patients with HTPR was significantly lower in the CDA group compared to the prasugrel group on discharge (2.3 vs 15.7%; p = 0.005). In addition fewer patients in the CDA group had a VASP < 16% on discharge (14.7 vs 50.5%; p <0.0001).

Conclusion: In the present study, PR monitoring was superior to standard prasugrel therapy to reduce the rate of HTPR in ACS patients. In addition such strategy reduced the number of patients with very low PR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2013.07.147DOI Listing
October 2013

High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes.

J Am Coll Cardiol 2011 Jul;58(5):467-73

Département de Cardiologie, Hôpital Universitaire Nord, Faculté de Médecine, Chemin des Bourrely, Marseille, France.

Objectives: The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events.

Background: Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y(12)-adenosine diphosphate receptor with a higher potency on PR.

Methods: A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month.

Results: Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70).

Conclusions: Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2011.04.017DOI Listing
July 2011

Relation of body mass index to high on-treatment platelet reactivity and of failed clopidogrel dose adjustment according to platelet reactivity monitoring in patients undergoing percutaneous coronary intervention.

Am J Cardiol 2009 Dec;104(11):1511-5

Département de Génétique Médicale, Hôpital de la Timone enfant, Marseille, France.

High on-treatment platelet reactivity (HTPR) after a clopidogrel loading dose predicts the risk of thrombotic events after percutaneous coronary intervention. We have demonstrated that HTPR could be overcome in most cases using dose adjustment according to PR monitoring resulting in an improved clinical outcome. However, this strategy failed in nearly 10% of patients with HTPR. Cytochrome P450 (CYP) 2C19 polymorphism was a major determinant of the response to clopidogrel and could be responsible for a failure of dose adjustment. We aimed to determine the clinical and genetical predictors of a failure of the dose-adjustment strategy. Seventy-three patients undergoing percutaneous coronary intervention were included in this prospective multicenter study. A vasodilator phosphoprotein index >or=50% after a 600-mg loading dose of clopidogrel defined HTPR. Dose adjustment was performed according to PR monitoring to reach a vasodilator phosphoprotein index <50%. Genetic polymorphism of CYP2C19 was determined by direct sequencing. Clinical predictors of HTPR were body mass index (BMI; p = 0.01), diabetes mellitus (p = 0.03), and acute coronary syndrome (p = 0.02). The mutant 2 allele of CYP2C19 681A > G loss of function polymorphism was also significantly associated with HTPR (p = 0.04). The rate of successful dose adjustment was similar in carriers of the CYP2C19 2 allele and carriers of the wild-type allele. The only independent predictor of a failed dose adjustment was a high BMI (p = 0.01). In conclusion, high BMI, acute coronary syndrome, diabetes mellitus, and CYP2C19 2 are associated with HTPR after a 600-mg loading dose of clopidogrel. Dose adjustment overcomes HTPR in carriers of the CYP2C19 2 allele. BMI is the only independent predictor of failed dose adjustment. Thus, drug underdosage seems to be the main determinant of HTPR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2009.07.015DOI Listing
December 2009

Combined Abciximab REteplase Stent Study in acute myocardial infarction (CARESS in AMI).

Am Heart J 2004 Sep;148(3):378-85

Royal Brompton Hospital, London, United Kingdom.

Background: Most patients with acute myocardial infarction (AMI) are admitted to hospitals without percutaneous transluminal coronary angioplasty (PTCA) facilities or are initially managed in a prehospital mobile unit. Thrombolysis remains the most readily available reperfusion treatment in those settings, but the optimal subsequent strategy in those patients is unclear. If a mechanical recanalization is likely to be performed in an emergency, it is probably desirable that the patient receives abciximab, the glycoprotein IIb/IIIa antagonist with the strongest evidence of benefit for angioplasty in AMI.

Objective: The aim of this trial is to compare the effects on clinical outcome and cost-effectiveness of 2 strategies after immediate treatment with abciximab and half-dose reteplase for ST-elevation AMI: to manage the patients conservatively (referring them for rescue PTCA only if needed) or to immediately send all patients for emergency coronary angioplasty.

Methods: The Combined Abciximab RE-teplase Stent Study in Acute Myocardial Infarction (CARESS in AMI) is an open, prospective, randomized, multicenter clinical trial conducted in patients with high-risk ST-segment elevation AMI treated within 12 hours from symptom onset in hospitals without PTCA facilities or in a prehospital mobile intensive care unit. Apart from contraindications to thrombolysis, the main exclusion criteria are age > or =75 years and a past history of CABG surgery or a percutaneous coronary intervention procedure involving the infarct-related artery. Enrollment will be performed in hospitals without PTCA facilities or directly in the ambulance if a dedicated system is in place for prehospital diagnosis and treatment of AMI. Patients will receive half-dose reteplase and full-dose abciximab and will subsequently be randomized to conventional medical therapy (with referral for emergency rescue PTCA allowed in selected cases) or emergency angioplasty. The primary end point is the 30-day combined incidence of mortality, reinfarction, and refractory ischemia. In order to obtain a 95% power (2-sided) to detect a 42% reduction in the primary end point, 900 patients are required in each arm of the study. Secondary end points include the 1-year composite end point of mortality, reinfarction, refractory ischemia, and hospital readmission because of heart failure; resource use at 30 days and 1 year; and the incidence of inhospital stroke and bleeding complications in the 2 groups.

Results: Seventy-four patients have been randomized (as of March 10, 2004); results are expected in June 2005.

Conclusion: This study will establish whether angioplasty must be started as soon as possible in all patients who receive combined pharmacologic reperfusion with the glycoprotein IIb/IIIa inhibitor abciximab and half-dose thrombolysis or whether it can be postponed or skipped in patients with signs of successful reperfusion, with obvious organizational advantages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2004.03.038DOI Listing
September 2004