Biomarkers of Thrombosis in ST-Segment Elevation Myocardial Infarction: A Substudy of the ATOLL Trial Comparing Enoxaparin Versus Unfractionated Heparin.

Background: The aim was to compare the peri-procedural biomarkers of coagulation and platelet activation in patients randomly allocated to intravenous enoxaparin or unfractionated heparin (UFH) in the ATOLL randomized trial (NCT00718471).

Methods And Results: A total of 129 patients (n = 58 enoxaparin and n = 71 UFH) admitted for ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) were included in this substudy of the ATOLL trial. Activated partial thromboplastin time ratio, anti-Xa activity, von Willebrand factor antigen, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor and soluble CD40 ligand were measured at sheath insertion (T1) and at the end of the PCI (T2) and correlated with 1-month clinical outcomes.

Clinical Outcome of First- vs Second-Generation DES According to DAPT Duration: Results of ARCTIC-Generation.

There is an apparent benefit with extension of dual antiplatelet therapy (DAPT) beyond 1 year after implantation of drug-eluting stents (DES). Assessment by a Double Randomization of a Conventional Antiplatelet Strategy vs a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation, and of Treatment Interruption vs Continuation One Year After Stenting (ARCTIC)-Generation assessed whether there is a difference of outcome between first- vs second-generation DES and if there is an interaction with DAPT duration in the ARCTIC-Interruption study. ARCTIC-Interruption randomly allocated 1259 patients 1 year after stent implantation to a strategy of interruption of DAPT (n = 624), in which aspirin antiplatelet treatment only was maintained, or DAPT continuation (n = 635) for 6 to 18 additional months.

Efficacy of ex vivo autologous and in vivo platelet transfusion in the reversal of P2Y12 inhibition by clopidogrel, prasugrel, and ticagrelor: the APTITUDE study.

Background: Allogenic platelet transfusions (PT) are administered to treat excessive bleeding in patients on P2Y12 receptor inhibitors (RI). We assessed the effect of ex vivo and in vivo PT on platelet activation and aggregation in patients on dual antiplatelet therapy.

Methods And Results: In the Antagonize P2Y12 Treatment Inhibitors by Transfusion of Platelets in an Urgent or Delayed Timing After Acute Coronary Syndrome or Percutaneous Coronary Intervention Presentation-Acute Coronary Syndrome (APTITUDE-ACS) study, patients presenting with acute coronary syndrome or for elective percutaneous coronary intervention, receiving loading doses of clopidogrel (600 mg, n=13 or 900 mg, n=12), prasugrel 60 mg (n=10), or ticagrelor 180 mg (n=10) were included.

Evaluation of the learning curve for transcatheter aortic valve implantation via the transfemoral approach.

Background: The aim of this study was to evaluate the learning curve in performing transfemoral TAVI (TF-TAVI).

Methods: Between October 2006 and October 2013, 312 consecutive TF-TAVI cases performed by 6 interventional cardiologists, using the Edwards Sapien valve and 104 using the CoreValve, were included in the present analysis. Cumulative sum (CUSUM) failure analysis of combined 30-day safety endpoint was used to evaluate learning curves.

Point-of-care genetic profiling and/or platelet function testing in acute coronary syndrome.

Our aim was to demonstrate that the sequential use of the Verigene® rapid CYP2C19 test for genetic profiling and the VerifyNowTM bedside test for platelet function measurement in ACS patients may optimise P2Y12 inhibition. "Rapid" (CYP2C19*1/*1 or CYP2C19*17 carriers, n=211) and "slow" metabolisers (CYP2C19*2 carriers, n=58) were first put on clopidogrel and prasugrel for ≥ 2 weeks, respectively. Patients with low platelet reactivity (PRU<30) on prasugrel or high platelet reactivity (>208 PRU) on clopidogrel were then switched to clopidogrel and prasugrel, respectively.

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

Background: 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.

Revisiting Sex Equality With Transcatheter Aortic Valve Replacement Outcomes: A Collaborative, Patient-Level Meta-Analysis of 11,310 Patients.

Background: There has been conflicting clinical evidence as to the influence of female sex on outcomes after transcatheter aortic valve replacement.

Objectives: The aim of this study was to evaluate the impact of sex on early and late mortality and safety end points after transcatheter aortic valve replacement using a collaborative meta-analysis of patient-level data.

Methods: From the MEDLINE, Embase, and the Cochrane Library databases, data were obtained from 5 studies, and a database containing individual patient-level time-to-event data was generated from the registry of each selected study.

Meta-Analysis of the Impact on Mortality of Noninfarct-Related Artery Coronary Chronic Total Occlusion in Patients Presenting With ST-Segment Elevation Myocardial Infarction.

Several observational studies have compared clinical outcome in patients with a co-existing noninfarct-related artery chronic total occlusion (n-IRA CTO) versus those without, suggesting increased all-cause mortality. The goal of this study was to provide a systematic review and meta-analysis evaluating the impact of the presence of an n-IRA CTO on short- and long-term mortality after primary percutaneous coronary intervention. Studies published from January 1980 to January 2014 that compared the incidence of all-cause mortality in patients with ST-segment elevation myocardial infarction with co-existing n-IRA CTO versus those without were identified using an electronic search and reviewed using meta-analytical techniques.

Usefulness of a Simple Clinical Risk Prediction Method, Modified ACEF Score, for Transcatheter Aortic Valve Implantation.

Background: We assessed the predictive accuracy of a simple risk score, modified age, creatinine clearance, ejection fraction (ACEFmodif) score, for outcome of transcatheter aortic valve implantation (TAVI).

Methods And Results: We prospectively included 703 consecutive patients undergoing TAVI. Patients were divided into low, middle and high ACEFmodif tertiles.

Impact of pre- and post-procedural anemia on the incidence of acute kidney injury and 1-year mortality in patients undergoing transcatheter aortic valve implantation (from the French Aortic National CoreValve and Edwards 2 [FRANCE 2] Registry).

Objectives: The relationship between anemia, renal insufficiency, and the outcomes of TAVI patients has not been thoroughly studied. We aimed to evaluate the influence of pre- and post-procedural anemia on the incidence of renal insufficiency, especially AKI, and on the outcomes of TAVI.

Methods: Data from the French national TAVI registry were collected in 3,472 patients who underwent TAVI between January 2010 and December 2012.

Effect of gender after transcatheter aortic valve implantation: a meta-analysis.

Background: The effect of gender on patients with aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) remains to be defined.

Methods: MEDLINE, Cochrane Library, and Scopus databases were searched for articles describing sex differences in baseline characteristics, procedures, and outcomes. All-cause death at follow-up of at least 1 year was the primary end point, and the independent effect of female gender was evaluated with pooled analysis using a random-effect model and with meta-regression.

Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial.

Background: Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial.

Methods: This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES).

Prasugrel but not high dose clopidogrel overcomes the lansoprazole neutralizing effect of P2Y12 inhibition: Results of the randomized DOSAPI study.

Aims: The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150 mg) would be less effective than switching to prasugrel 10 mg maintenance dose (MD) to overcome this negative interaction.

Method And Results: In a randomized study with a factorial design, 82 stable coronary artery disease patients treated with 75 mg clopidogrel MD and aspirin were assigned to receive in a double blind fashion lansoprazole (30 mg/day) or placebo and to receive in an open fashion 150 mg clopidogrel MD or 10 mg prasugrel MD.

High on-treatment platelet reactivity as a risk factor for secondary prevention after coronary stent revascularization: A landmark analysis of the ARCTIC study.

Background: Individualizing antiplatelet therapy after platelet function testing did not improve outcome after coronary stenting in the Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting (ARCTIC) study. Whether results are different during the phase of secondary prevention starting after hospital discharge, when periprocedural events have been excluded, is unknown.

Methods And Results: In ARCTIC, 2440 patients were randomized before coronary stenting to a strategy of platelet function monitoring (VerifyNow P2Y12/aspirin point-of-care assay) with drug adjustment in suboptimal responders to antiplatelet therapy or to a conventional strategy without monitoring and without drug or dose changes.

Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis.

Objective: To investigate the effect of pretreatment with P2Y12 receptor inhibitors compared with no pretreatment on efficacy and safety of treatment of non-ST elevation acute coronary syndrome (ACS).

Data Sources: Two reviewers independently searched Medline, Embase, Cochrane Controlled Trials, and BioMed Central databases for randomized placebo controlled trials and observational studies from August 2001 to March 2014.

Study Eligibility: Studies must have reported both all-cause mortality (primary efficacy endpoint) and major bleeding (safety endpoint) outcomes.

Impact of red blood cell transfusion on platelet aggregation and inflammatory response in anemic coronary and noncoronary patients: the TRANSFUSION-2 study (impact of transfusion of red blood cell on platelet activation and aggregation studied with flow cytometry use and light transmission aggregometry).

Objectives: This study sought to determine whether red blood cell (RBC) transfusion increases in vivo platelet aggregation and inflammation in coronary and noncoronary patients.

Background: RBC transfusion increases in vitro platelet activation and aggregation in healthy volunteers, providing a possible explanation for the increase in recurrent ischemic events and mortality reported after RBC transfusion in patients with acute coronary syndromes (ACS).

Methods: Platelet reactivity was measured before and after RBC transfusion in 61 patients (33 with ACS patients and 28 without ACS).

Switching acute coronary syndrome patients from prasugrel to clopidogrel.

Objectives: This study sought to assess the consequences of switching prasugrel to clopidogrel on platelet inhibition and clinical outcomes after an acute coronary syndrome (ACS).

Background: Many ACS patients are switched from prasugrel to clopidogrel within the recommended 1-year duration of treatment.

Methods: Platelet reactivity was measured with the VerifyNow P2Y(12) assay (Accumetrics, San Diego, California) in 300 ACS patients treated for 15 days with prasugrel 10 mg.

Association of clopidogrel pretreatment with mortality, cardiovascular events, and major bleeding among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

Context: Clopidogrel pretreatment is recommended for patients with acute coronary syndromes (ACS) and stable coronary artery disease who are scheduled for percutaneous coronary intervention (PCI), but whether using clopidogrel as a pretreatment for PCI is associated with positive clinical outcomes has not been established.

Objective: To evaluate the association of clopidogrel pretreatment vs no treatment with mortality and major bleeding after PCI.

Data Sources: MEDLINE, EMBASE, Cochrane Controlled Trials Register databases, and reference lists of qualifying articles.

Impact of transfer time on mortality in acute coronary syndrome with ST-segment elevation treated by angioplasty.

Background: In primary percutaneous coronary intervention (pPCI), conflicting data exist on the relative importance of patient presentation time (time from symptom onset (SO) to first medical contact [FMC]) and transfer time (time from FMC to sheath insertion).

Objectives: To evaluate the impact of transfer time on mortality in an unselected ST-elevation myocardial infarction (STEMI) population treated with pPCI.

Methods: In a well-organized urban network, using mobile intensive care units (MICU) whenever possible, the impact of transfer time on inhospital mortality was evaluated in 703 unselected consecutive STEMI patients transferred for pPCI.

Bedside monitoring to adjust antiplatelet therapy for coronary stenting.

Background: Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy.

Methods: We randomly assigned 2440 patients scheduled for coronary stenting at 38 centers 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.

Prasugrel monitoring and bleeding in real world patients.

The aim of this study was to evaluate platelet reactivity and 30-day bleeding events in patients treated with prasugrel 10 mg after acute coronary syndromes. A total of 444 patients with acute coronary syndromes treated with percutaneous coronary intervention and prasugrel 10 mg/day were monitored by measurement of the vasodilator-stimulated phosphoprotein (VASP) index 2 to 4 weeks after hospital discharge. Platelet reactivity was also assessed using the VerifyNow P2Y(12) assay and light transmission aggregometry.

Pharmacogenetics of clopidogrel.

Clopidogrel used in conjunction with aspirin has a central role in the treatment of patients with an acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). The pharmacokinetic and pharmacodynamic responses to this drug are highly variable leaving up to one third of patients with inadequate platelet inhibition or high on-treatment platelet reactivity (HPR), and subsequent increased ischemic cardiovascular events. Genetic variability in drug absorption and metabolism is a key factor responsible for the inefficient generation of the active drug metabolite.

An evidence-based review of current anti-platelet options for STEMI patients.

Drug-eluting stents are the default treatment for acute coronary syndromes, unless concerns or contraindications preclude dual antiplatelet therapy (DAPT). Platelet microemboli and mediators from activated platelets can undermine the restoration of perfusion. Therefore, ST-segment elevation MI (STEMI) patients should receive antiplatelet treatments regardless of reperfusion strategy.

High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study.

Aims: The aim of this study was to compare on-thienopyridine platelet reactivity of elderly patients (≥75 years) vs. younger patients (<75 years). Elderly patients represent a growing and challenging segment of the coronary population for whom the effect of dual antiplatelet therapy on platelet inhibition has not been specifically addressed.

Antiplatelet options for secondary prevention in acute coronary syndromes.

Current guidelines recommend dual antiplatelet therapy, a combination of aspirin and a P2Y(12) inhibitor, for 6?12 months after percutaneous coronary intervention with drug-eluting stent implantation in all patients and for 1 year in all patients after an acute coronary syndrome (ACS), irrespective of revascularization strategy. Clopidogrel has a pharmacokinetic and pharmacodynamic profile that results in a delayed and/or subtherapeutic antiplatelet effect, and wide variability in antiplatelet response. New P2Y(12) inhibitors, such as prasugrel and ticagrelor, have favorable pharmacodynamics and clinical efficacy over clopidogrel and offer an alternative antiplatelet treatment strategy in specific patients.