Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study

International audienceBACKGROUND:The ARCTIC study randomized 2440 patients scheduled for stent implantation to a strategy of platelet function monitoring with drug adjustment in patients who had a poor response to antiplatelet therapy or to a conventional strategy without monitoring and drug adjustment. No significant improvement in clinical outcomes with platelet function monitoring was observed.OBJECTIVE:The purpose of this study is to assess the relationships between CYP2C19 genotypes, clopidogrel pharmacodynamic response, and clinical outcome.METHODS AND RESULTS:In the ARCTIC-GENE study, 1394 patients were genotyped for loss- and gain-of-function CYP2C19 alleles. Randomization of treatment strategy was well balanced. Slow metabolizers identified as carriers of at least one loss-of-function allele CYP2C19*2 (n = 459) were more likely poor responders at randomization (41.6 vs. 31.6%, p = 0.0112) and 14 days later (23.8 vs. 10.4%, p < 0.0001) and more frequently on prasugrel (11.5 vs. 8.1%, p = 0.039) as compared with rapid metabolizers (n = 935). Intensification of antiplatelet treatment did not differ between slow and rapid metabolizers according to the study algorithm based on platelet function only. The primary study outcome defined as the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation did not differ between slow and rapid metabolizers (HR 0.988, 95% CI [0.812;1.202], p = 0.90). Likewise, the primary safety outcome did not differ between rapid and slow metabolizer phenotype.CONCLUSIONS:The genetic clopidogrel profile was a good marker of platelet function response on clopidogrel but was not related to clinical outcome suggesting that the genetic added little to the pharmacodynamic information used in the study to adjust antiplatelet therapy. ClinicalTrials.gov: NCT00827411

De FRANCE 2 à FRANCE TAVI : les indications, la technique et les résultats du remplacement valvulaire aortique percutané sont-ils les mêmes ?

National audiencePoints essentiels Les procédures de remplacement valvulaire aortique percutané (TAVI) doivent être proposées à des patients porteurs d’un rétrécissement aortique serré symptomatique présentant une contre-indication au remplacement valvulaire chirurgical ou ayant un risque opératoire jugé élevé en réunion de concertation pluridisciplinaire. On note une diminution de l’EuroSCORE moyen depuis janvier 2010, diminution qui traduit déjà une évolution progressive dans la sélection des patients. S’agissant d’une population âgée (moyenne d’âge : 83,4 ± 7,3 ans), l’expertise des gérontologues peut être importante et l’évaluation de la « fragilité » fait partie du bilan. La voie fémorale est utilisée dans 80 % des cas avec un taux de succès procédural supérieur à 95 %. Le taux de mortalité hospitalière est de 5,9 %. Les complications sont essentiellement représentées par le risque de rupture d’anneau (0,9 % dans FRANCE TAVI), le risque de tamponnade (2,3 %), le risque d’accident vasculaire cérébral (2,2 %), le risque de fuite péri-prothétique importante (1,2 %), le risque d’implantation de pacemaker (14,4 %). Les résultats attendus de la cohorte A de PARTNER II et de SURTAVI pourront conduire à élargir les indications à des patients à moindre risque s’il est montré que le TAVI fait aussi bien que la chirurgie dans cette population ce que le récent essai randomisé NOTION suggère alors que le CoreValve Pivotal Trial va même dans le sens d’une possible supériorité de la technique percutanée. Key points Transcatheter aortic valve implantation (TAVI) is indicated in patients with severe symptomatic aortic stenosis who are not suitable for surgery or should be considered when there is a high surgical risk as assessed by a heart team. There is a decrease in mean logistic EuroSCORE since January 2010, which translates a gradual evolution in patients’ selection. Expertise of geriatricians to further assess frailty is a key step in the risk stratification process of this elderly population (mean age: 83.4 ± 7.3 years). Femoral access is used in 80% of cases with a procedural success rate higher than 95%. In-hospital mortality rate is 5.9%. The main complications of the procedure are aortic annulus rupture (0.9% in FRANCE TAVI), tamponade (2.3%), stroke (2.2%), severe paravalvular leak (1.3%) and permanent pacemaker implantation (15%). The awaited results of PARTNER II and SURTAVI may lead to expand the indications to lower-risk patients if it is shown that TAVI is non-inferior to surgery in this population which has been suggested by the recent randomized NOTION Trial while the CoreValve Pivotal Trial even points in the direction of a possible superiority of the percutaneous technique over surger

Long-Term Mortality and Early Valve Dysfunction According to Anticoagulation Use

International audienc

ST-Segment Elevation Myocardial Infarction Following Transcatheter Aortic Valve Replacement

International audienc

Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease

International audienc

Temporal Trends in Transcatheter Aortic Valve Replacement in France: FRANCE 2 to FRANCE TAVI

International audienceBackground - Transcatheter aortic valve replacement (TAVR) is standard therapy for patients with severe aortic stenosis who are at high surgical risk. However, national data regarding procedural characteristics and clinical outcomes over time are limited. Objectives - The aim of this study was to assess nationwide performance trends and clinical outcomes of TAVR during a 6-year period. Methods - TAVRs performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (French Transcatheter Aortic Valve Implantation) registry. Findings were further compared with those reported from the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry, which captured all TAVRs performed from January 2010 to January 2012 across 34 centers. Results - A total of 12,804 patients from FRANCE TAVI and 4,165 patients from FRANCE 2 were included in this analysis. The median age of patients was 84.6 years, and 49.7% were men. FRANCE TAVI participants were older but at lower surgical risk (median logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 15.0% vs. 18.4%; p < 0.001). More than 80% of patients in FRANCE TAVI underwent transfemoral TAVR. Transesophageal echocardiography guidance decreased from 60.7% to 32.3% of cases, whereas more recent procedures were increasingly performed in hybrid operating rooms (15.8% vs. 35.7%). Rates of Valve Academic Research Consortium-defined device success increased from 95.3% in FRANCE 2 to 96.8% in FRANCE TAVI (p < 0.001). In-hospital and 30-day mortality rates were 4.4% and 5.4%, respectively, in FRANCE TAVI compared with 8.2% and 10.1%, respectively, in FRANCE 2 (p < 0.001 for both). Stroke and potentially life-threatening complications, such as annulus rupture or aortic dissection, remained stable over time, whereas rates of cardiac tamponade and pacemaker implantation significantly increased. Conclusions - The FRANCE TAVI registry provided reassuring data regarding trends in TAVR performance in an all-comers population on a national scale. Nonetheless, given that TAVR indications are likely to expand to patients at lower surgical risk, concerns remain regarding potentially life-threatening complications and pacemaker implantation. (Registry of Aortic Valve Bioprostheses Established by Catheter [FRANCE TAVI]; NCT01777828)