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Background There are limited data on outcomes following primary percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEMI) in nonagenarian patients. Methods and Results We conducted a multicentre retrospective study between 2006 and 2013 in 5 international high-volume centers and included 145 nonagenarians treated with primary PCI for STEMI. Cardiogenic shock was present at admission in 21%. Mean delay between symptom onset and balloon was 5,8±7,6 hours and 60% of procedures were performed through the transradial approach. Successful revascularization of the culprit vessel was obtained in 86% of the cases (TIMI flow of 2 or 3). Major or clinically-relevant bleeding was observed in 4% of patients. Mean cardiac troponin Ic was 65±79 ng/ml and mean LVEF post-PCI was 42±13%. The in-hospital mortality was 24% with 6 months and 1 year survival of 58% and 49% respectively. Conclusions In our study, primary PCI in nonagenarians with STEMI was successful and feasible through a transradial approach. It is associated with a high rate of successful reperfusion of the infarct-related artery and nearly 50% survival at one year. These results suggest that primary PCI should be offered in selected nonagenarians with acute myocardial infarction (table next page). Abstract 0443 – Table Procedural Findings Time from symtoms to PCI (h) 5.8±7.6 Catheterizzation access (%) Radial 60 Single Vessel Coronary Disease (%) 53 Single Vessel Coronary PCI (%) 74 Infarct-related coronary artery (%) Left main 4 Left anterior descending 41 Circumflex 14 Right 45 CABG 3 Thrombus aspiration (%) 14 TMI flow grade after procedure (%) 0 12 1 1 2 6 3 81 Coronary stenting (%) BMS 75 DES 9 POBA 10 Procedure success (%) Successful PCI 86 Failed PCI 11 Complicated PCI 3 Use of protection device (%) 2 IABP (%) 0 Use of inotropes during procedure (%) 26

Although Clopidogrel pretreatment is recommended for ACS and stable coronary patients scheduled for PCI, the benefit of this strategy compared to an administration at the time of PCI has not been shown on hard clinical outcome. We performed a systematic review and meta-analysis of all RCTs and

Intravenous enoxaparin did not reduce significantly the primary end point (p = 0.06) compared with unfractionated heparin (UFH) in the randomized Acute Myocardial Infarction Treated with primary angioplasty and intravenous enoxaparin Or unfractionated heparin to Lower ischemic and bleeding events at short- and Long-term follow-up (ATOLL) trial. We present the results of the prespecified per-protocol analysis excluding patients who did not receive the treatment allocated by randomization or received both enoxaparin and UFH. We evaluated all-cause mortality, complication of myocardial infarction, procedural failure, or major bleeding (primary end point) and all-cause mortality, recurrent acute coronary syndrome, or urgent revascularization (main secondary end point). Baseline and procedural characteristics were well balanced between the 2 treatment groups. Of 910 randomized patients, 795 patients (87.4%) were treated according to the protocol with consistent anticoagulation using intravenous enoxaparin (n = 400) or UFH (n = 395). Enoxaparin reduced significantly the rates of the primary end point (relative risk [RR] 0.76, 95% confidence interval [CI] 0.62 to 0.94, p = 0.012) and the main secondary end point (RR 0.37, 95% CI 0.22 to 0.63, p0.0001). There was less major bleeding with enoxaparin (RR 0.46, 95% CI 0.21 to 1.01, p = 0.050) contributing to the significant improvement of the net clinical benefit (RR 0.46, 95% CI 0.3 to 0.74, p = 0.0002). All-cause mortality was also reduced with enoxaparin (RR 0.36, 95% CI 0.18 to 0.74, p = 0.003). In conclusion, in the per-protocol analysis of the ATOLL trial, pertinent to87% of the study population, enoxaparin was superior to UFH in reducing ischemic end points and mortality.

We aimed to assess whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of cardiovascular (CV) events in stable patients with established atherothrombosis or multiple risk factors.We analysed the 23,728 European patients of the REACH Registry; 20,588 (86.8%) had established atherothrombotic disease and 3140 (13.2%) had multiple risk factors only. Aspirin (ASA) and/or NSAIDs use was determined at enrolment and ischemic events were recorded over two years of follow-up. cMACCE was defined as the composite of CV death, MI or stroke. Bleeding was defined as any bleeding leading to both hospitalisation and transfusion.The mean age of population was 67.2±9.8years. At baseline, 1573 patients (6.6%) received NSAIDs and 15,395 (64.9%) received ASA. Four groups were defined: 1) no ASA/no NSAIDs, 2) ASA only, 3) NSAIDs only, 4) NSAIDs+ASA, with 7722 (32.5%), 14,433 (60.8%), 611 (2.6%) and 962 (4.1%) patients in these groups, respectively. Among the 22,028 (92.8%) with complete 2-year follow-up, 683 (3.2%) died from CV causes, while 395 (1.9%) had MI, 665 (3.1%) stroke, 1651 (7.6%) cMACCE and 199 (1.0%) bleeding. After adjustment, NSAID use was independently associated with an increased risk of stroke (OR 1.635; 95% CI 1.239-2.159, p0.001), and a trend towards an increased bleeding rate (OR 1.554; CI 95% 0.960-2.51, p=0.07). No association was found between NSAID use and MI or MACCE.In stable atherothrombosis patients, the use of NSAIDs appears to be independently associated with an increased cerebrovascular event risk.

Introduction The reperfusion strategy requiring primary percutaneous coronary intervention (PPCI) for ST-segment elevation acute myocardial infarction (STEMI) in nonagenarian patients remains controversial. The purpose of this study was to evaluate the results and the outcome of PPCI in patients aged 90 years old or more with STEMI. Methods We conducted a monocentric retrospective study over the past 8 years and focused on nonagenarians treated with PPCI for STEMI. Results We enrolled 34 patients with STEMI who were treated with PPCI. Mean age was 92.7±2,5 years, 74% were women. Cardiogenic shock was present at admission in 9 (26%) of these patients, acute pulmonary oedema was diagnosed in 10 (29%) of them and 2 (6%) had severe conduction disorder. Mean delay between symptom onset and balloon was 92±12.7 hours and 29 patients (83%) underwent PCI through transradial approach. Among these patients, 16 (46%) had monotroncular coronary heart disease and 31 (89%) had single-vessel PCI (3% LM, 53% LAD, 15% CX and 29% RCA). Revascularization procedure of the culprit vessel was successful in 88% of the cases (TIMI flow of 2 or 3). Bare-metal stents were implanted in 30 cases (94%) versus in 1 case (3%) for drug-eluting stents. Distal embolization occurred in 2 patients (6%) and acute coronary dissection occurred in 2 other cases (6%) but only one patient (3%) had severe bleeding despite the use of clopidogrel in 31 cases (89%) and anti-GpIIb-IIIa in 17 cases (50%). None had intra-aortic counterpulsation support. Mean cardiac troponine Ic was 90±105 ng/ml and mean LVEF post-PCI was measured at 43±14%. Mean hospital stay was 4.8±4.6 days and in-hospital mortality rate was 24%. Conclusion In our study, PPCI in nonagenarians with STEMI is successful and feasible through a transradial approach. It is associated with high rate of successful reperfusion of the infarct-related artery. These results suggest that PPCI should be offered in selected nonagenarians with STEMI.

Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy.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. The primary end point was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation. For patients in the monitoring group, the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later.In the monitoring group, high platelet reactivity in patients taking clopidogrel (34.5% of patients) or aspirin (7.6%) led to the administration of an additional bolus of clopidogrel, prasugrel, or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure. The primary end point occurred in 34.6% of the patients in the monitoring group, as compared with 31.1% of those in the conventional-treatment group (hazard ratio, 1.13; 95% confidence interval [CI], 0.98 to 1.29; P=0.10). The main secondary end point, stent thrombosis or any urgent revascularization, occurred in 4.9% of the patients in the monitoring group and 4.6% of those in the conventional-treatment group (hazard ratio, 1.06; 95% CI, 0.74 to 1.52; P=0.77). The rate of major bleeding events did not differ significantly between groups.This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).

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. Bleeding events (per the Bleeding Academic Research Consortium [BARC] definition) and ischemic events (death, myocardial infarction, and definite stent thrombosis) were collected over 30 days of follow-up. Two thirds of the patients presented with ST-segment elevation myocardial infarctions, 28.8% had diabetes, and 12.4% were aged >75 years. High on-treatment platelet reactivity according to 3 prespecified definitions (VASP index ≥50%, platelet reactivity ≥235 P2Y 12 reaction units, and residual platelet reactivity ≥46.2%) was found in 6.8%, 3.4%, and 3.2% of patients, respectively. Obesity (body mass index >30 kg/m 2 ) and multivessel disease were the only independent factors associated with high on-treatment platelet reactivity (p = 0.006 and p = 0.045, respectively). At 30 days, there was no major bleeding complication (BARC grade 3 or 5), and 1.6% of patients had recurrent ischemic events. Nuisance bleeding (BARC grade 1) and minor bleeding (BARC grade 2) occurred in 14.2% (n = 63) and 2.5% (n = 11) of patients, respectively, but were not predicted by VASP index. In conclusion, patients with acute coronary syndromes receiving maintenance doses of prasugrel have low rates of HPR and ischemic events within the first month. Minor or minimal bleeding is frequent, but not major bleeding. VASP was poorly correlated with the risk for minor or minimal bleeding.

Acute coronary syndrome (ACS) is still a serious condition associated with decreased quality of life, increased healthcare expenditures, and premature death. The prevalence of ACS is expected to increase with aging of the population and with the epidemics of obesity and diabetes. The short- and long-term mortality after an ACS has been dramatically reduced by the development of revascularization techniques and new antithrombotic agents. The past decade has seen many trials evaluating new oral and parenteral antiplatelet agents with greater potency than aspirin and clopidogrel. Several antiplatelet agents have been developed, with the ultimate goal to obtain optimal antiplatelet therapy for both the acute and the chronic phases of disease. Articles see p 336, 347 Ideally, efficiency requires several pharmacodynamic proprieties, such as a fast onset of action (immediate onset for emergency situations), a strong degree of platelet inhibition (at least stronger than the standard of care [aspirin and clopidogrel]), a narrow interindividual variability with no impact of genetic variants and no drug-to-drug interaction, and an easy administration (an oral drug for maintenance therapy and an intravenous formulation for rapid loading). Of course, this drug should also lead to a convincing reduction of recurrent ischemic events in an adequately powered phase 3 trial. With regard to safety, the illusion of having the same dose of a single antiplatelet drug to treat all clinical situations has passed. The degree of platelet activation and aggregation is different across clinical situations (eg, acute ST-segment–elevation myocardial infarction [STEMI] versus secondary prevention) and varies over time in the same patient. Recent large phase 3 trials have confirmed the importance of dosing and the target population treated with the new agents.1–4 From a safety standpoint, an ideal antiplatelet agent would also have an intravenous and oral formulation, with different doses tested in …

Primary percutaneous coronary intervention (PCI) is the treatment of choice for patients presenting with acute ST-segment elevation myocardial infarction (STEMI). However, if catheterization facilities are not immediately available, the effectiveness of PCI can be affected by delays in transfer. Evidence suggests that antiplatelet therapy administered early, preferably in the ambulance during transfer, may provide better and earlier perfusion. Ticagrelor, a direct platelet P2Y12 receptor inhibitor, is indicated for the management of patients with acute coronary syndromes. The ATLANTIC study (NCT01347580; EudraCT 2011-000214-19) is a 30-day international, randomized, parallel-group, placebo-controlled study in male and female patients (aged ≥18 years) who are diagnosed as having STEMI, with intended primary PCI. In total, 1770 patients will be randomized immediately after diagnosis to prehospital administration of ticagrelor 180 mg followed by matching placebo administered in hospital, or prehospital administration of placebo followed by ticagrelor 180 mg administered in hospital. All patients will then receive ticagrelor 90 mg twice daily for 30 days. The coprimary end point is the percentage of patients reaching thrombolysis in myocardial infarction flow grade 3 in the infarct-related artery at initial angiography or achieving ≥70% ST-segment elevation resolution pre-PCI. The primary safety end point is major, life-threatening, or minor bleeding after ticagrelor administration. The results of this study may have an impact on future recommendations for treatment for patients with STEMI.

Non-ST elevation (NSTE) myocardial infarction and unstable angina are the most common clinical presentations of acute coronary syndrome (ACS). Platelet activation is central to the pathogenesis of NSTE-ACS and consensus guidelines that advocate early revascularization supported by intensive antiplatelet therapy. This review examines the drugs used concurrently with aspirin as dual antiplatelet therapy in the NSTE-ACS setting. Clopidogrel represented an important therapeutic advance. However, variations in platelet response and a relatively slow onset of action compromise outcomes with clopidogrel. Evidence reviewed in this article shows that in NSTE-ACS patients, ticagrelor and prasugrel are more effective than clopidogrel and are relatively well tolerated, with an acceptable and manageable bleeding risk. The literature suggests several differences between ticagrelor and prasugrel that should allow clinicians to better tailor treatment to the patient. Head-to-head comparisons are now needed to compare directly the risks and benefits of ticagrelor and prasugrel in NSTE-ACS. Further studies also need to address other outstanding issues such as the benefits and risks of prasugrel pre-treatment and to stratify efficacy and tolerability according to diabetes mellitus (DM) and other co-morbidities. In the meantime, the issues discussed in this review should enhance clinicians' ability to optimize and individualize NSTE-ACS treatment, thereby further reducing the morbidity and mortality associated with this common cardiovascular condition.

Summary 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. Results Our STEMI population included patients with cardiogenic shock (5.3%) and out-of-hospital cardiac arrest (3.7%). Longer transfer times were found to be associated with a stepwise increase in mortality ranging from 2.99% in the first quartile (Q1) up to 8.65% in the fourth quartile (Q4) ( P = 0.005). This result was noted in patients presenting early (≤ 2 h of SO, 0.96% for Q1 vs. 9.8% for Q4, P = 0.006) but not in late presenters (> 2 h of SO, 7.00% for Q1 vs. 7.8% for Q4, P = 0.85). After adjustment for confounding variables such as the severity of patients, the relationship between mortality and transfer time was no longer apparent. Conclusions In a well-organized urban network dedicated to pPCI, including unselected STEMI patients, transfer time does not appear to be a major contributor to mortality. The relationship of transfer time to mortality seems to be dependent on presentation time and patients’ clinical severity.

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. The two-step hepatic cytochrome P450 (CYP)-dependant oxidative metabolism of the prodrug appears to be of particular importance. Pharmacogenomic analyses have identified loss-of-function variant alleles of CYP 2C19 and specifically the 2C19*2 allele, to be the predominant genetic mediators of the antiplatelet effect of clopidogrel. Carriers were have been shown to have lower active metabolite levels of clopidogrel, higher platelet reactivity and associated poorer outcomes. Rapid and accurate point-of-care genetic tests to identify these alleles are currently in development but several questions about the role of such testing remain such as patient selection and whether personalized treatment based on genotype has a positive impact on clinical outcome. At present, genetic testing cannot be recommended in routine clinical practice due to insufficient prospective data. However, the significant body of research published to date suggests a likely role when used in combination with platelet function analysis in ACS patients undergoing stenting who have other known risk factors for recurrent ischemic events.

MOTS CLES Infarctus myocarde ; Anticoagulation ; Heparine ; Heparine de bas poids moleculaire ; Bivalirudine Rates of shortand long-term mortality after an acute coronary syndrome (ACS) have been reduced dramatically through advances in percutaneous coronary intervention (PCI) techniques and the availability of new antithrombotic agents. This is particularly true for patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI. On the antiplatelet side, we have, besides clopidogrel, two new P2Y12 inhibitors — prasugrel and ticagrelor — for which data and subset analyses have allowed a better understanding of which patients with an ACS would truly benefit from these drugs. On the anticoagulant side, besides unfractionated heparin (UFH), we have three newer anticoagulants that can be used in ACS: enoxaparin, fondaparinux and bivalirudin. In this competitive field, the past decade has provided a large flow of evidence-based information in terms of the safety and efficacy of these antithrombotic agents. This information needs to be implemented both in guidelines and in our daily clinical practice. As always, there is no simple rule or conclusion; rather, different options exist according to current practice and our own personal environment and experiences. The efficacy of anticoagulation therapy is evaluated on the basis of ischaemic complications of ACS and sometimes the outcome of PCI itself, both of which have a real impact on shortand long-term mortality. The first goal of anticoagulation therapy during primary PCI of STEMI is therefore to avoid or control at all times the development of thrombus and in doing so obtain or maintain blood flow through the coronary circulation and protect the myocardium from harmful damage related to ischaemia and necrosis. If the drug efficacy translates into a mortality reduction, there is a good chance of recognition and acceptation of the new treatment by practising physicians.

Material and Methods: From September 2010 to Mars 2011, we prospectively included all patients below 50 years old admitted for ACS at the University Hospital of Toulouse, France and assessed their use of Marijuana by medical questioning and systematic urinary assay. Patients were divided into 2 groups (marijuana smokers and no marijuana smokers) according to the presence of marijuana in urines. Parametric and non-parametric tests were used for groups comparison.

including age, sex and time delays to admission. Interestingly, dyslipidemia and history of MI was less frequent in PE group. Plasma CRP levels on admission were markedly higher in PE patients. Prior chronic treatments were less frequent in PE group, in particular for aspirin (11 vs 19%, p=0.027), ACE inhibitor (10 vs 18%, p=0.014) and statin (15 vs 23%, p=0.054). Acute treatments were similar, except for BetaBlocker that were more used in patients without PE. Patients with PE were more likely to suffer from STEMI and altered LVEF. Hospital complications such as death, or heart failure (12 vs 7%, p=0.016, 47 vs 28%, p=0.001), and mechanical complications including atrial fibrillation, wall rupture, apical thrombus and mitral regurgitation (respectively, 20 vs 9%, p

Despite dual antiplatelet therapy, stent thrombosis remains a devastating and unpredictable complication of percutaneous coronary intervention (PCI).To perform a sequential analysis of clinical and genetic factors associated with definite early stent thrombosis.Case-control study conducted in 10 centers in France between January 2007 and May 2010 among 123 patients undergoing PCI who had definite early stent thrombosis and DNA samples available, matched on age and sex with 246 stent thrombosis-free controls.Accuracy of early stent thrombosis prediction by 23 genetic variants.Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (adjusted odds ratio [OR], 1.99; 95% CI, 1.47-2.69), ABCB1 3435 TT genotype (adjusted OR, 2.16; 95% CI, 1.21-3.88), and ITGB3 PLA2 carriage (adjusted OR, 0.52; 95% CI, 0.28-0.95). Nongenetic independent correlates were acuteness of PCI (adjusted OR, 3.05; 95% CI, 1.54-6.07), complex lesions (American College of Cardiology/American Heart Association type C) (adjusted OR, 2.33; 95% CI, 1.40-3.89), left ventricular function less than 40% (adjusted OR, 2.25; 95% CI, 1.09-4.70), diabetes mellitus (adjusted OR, 1.82; 95% CI, 1.02-3.24), use of proton pump inhibitors (adjusted OR, 2.19; 95% CI, 1.29-3.75), and higher clopidogrel loading doses (adjusted OR, 0.73; 95% CI, 0.57-0.93). The discriminative accuracy of the clinical-only model was similar to that of a genetic-only model (area under the curve, 0.73 [95% CI, 0.67-0.78] vs 0.68 [95% CI, 0.62-0.74], respectively; P = .34). A combined clinical and genetic model led to a statistically significant increase in the discriminatory power of the model compared with the clinical-only model (area under the curve, 0.78 [95% CI, 0.73-0.83] vs 0.73 [95% CI, 0.67-0.78]; P = .004).This case-control study identified 3 genes (CYP2C19, ABCB1, and ITGB3) and 2 clopidogrel-related factors (loading dose and proton pump inhibitors) that were independently associated with early stent thrombosis. Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts.

Background— Reduced concentrations of clopidogrel active metabolite have been associated with diminished platelet inhibition and higher rates of adverse cardiovascular events. Paraoxonase-1 (PON1) has recently been proposed as a key enzyme for clopidogrel metabolic activation. We tested the effects of PON1 polymorphisms on clopidogrel pharmacokinetics and pharmacodynamics and the occurrence of cardiovascular outcomes in young post–myocardial infarction (MI) patients treated with clopidogrel. Methods and Results— We genotyped PON1 (Q192R and L55M) and CYP2C19 variants in 106 patients enrolled in the PK/PD CLOVIS-2 trial. Patients were randomly exposed to a 300-mg or 900-mg clopidogrel loading dose in a crossover study design. Clopidogrel active metabolite isomer H4 (clopi-H4) and platelet function testing were measured serially after loading dose. There was no significant association between PON1 Q192R or L55M and clopi-H4 formation or antiplatelet response to clopidogrel after either loading dose. Using multivariable linear regression analyses, the CYP2C19*2 allele was the only predictor of clopi-H4 generation and platelet response irrespective of the platelet function assay. CYP2C19 loss-of-function but not PON1 variants were significantly associated with increased risk of major cardiovascular events (death, MI, and urgent coronary revascularization) occurring during long-term clopidogrel exposure in 371 young post-MI patients (age CYP2C19 loss-of-function allele carrier versus noncarrier: hazard ratio, 2.26; 95% confidence interval, 1.15–4.41, P =0.02; PON1 QQ192 versus QR/RR192: hazard ratio, 1.03; 95% confidence interval, 0.50–2.11, P =0.93; PON1 LL55 versus LM/MM55: hazard ratio, 1.52; 95% confidence interval, 0.75–3.08, P =0.24). Conclusions— Our study does not confirm that PON1 Q192R or L55M can influence clopidogrel pharmacokinetics or pharmacodynamics in post-MI patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00822666.

Background Aldosterone levels are high early after admission for ST elevation myocardial infarction (STEMI) concomitantly with high risk of sudden death and life-threatening ventricular arrhythmia. Methods We assessed the hypothesis that early aldosterone blockade on admission for primary percutaneous coronary intervention (PCI) may be associated with a reduction of life-threatening ventricular arrhythmia in a prospective cohort-nested case (n=159) versus historical control (n=623) study. All cases were treated on admission by 200mg IV bolus of potassium canrenoate, followed by 25mg PO spironolactone daily during the coronary care unit stay. The primary endpoint – in-hospital composite of death, resuscitated cardiac arrest and ventricular tachycardia – was assessed by logistic regression models adjusted on major pre-specified variables and validated by a bootstrap procedure and propensity-score based analyses. Results Aldosterone blockade was associated with lower risks of the primary endpoint (adjusted ORs 0.26, 95% CI [0.13–0.57]), resuscitated cardiac arrest (adjusted OR 0.39, 95% CI [0.16–0.94]), ventricular tachycardia or fibrillation (adjusted ORs 0.23, 95% CI [0.12–0.45]), as well as ventricular arrhythmia requiring resuscitation or anti-arrhythmic therapy (adjusted OR 0.41, 95% CI [0.19–0.88]). All findings were confirmed by the bootstrap procedure. The benefit on death or resuscitated cardiac arrest seemed sustained at 6month follow-up. Conclusions Early aldosterone blockade in patients presenting for primary PCI for STEMI is associated with significant reductions in rates of life-threatening arrhythmia and cardiac arrest independent of the initial risk profile, heart failure or hemodynamic status. These findings support the concept of aldosterone blockade early after STEMI, warranting further confirmation by ongoing randomized trials.

To determine the incidence, type and possible association with mortality of major bleeding in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with an invasive strategy using predominantly the radial approach and triple antiplatelet therapy.In the multicentre randomised ABOARD Study, 352 patients with NSTE-ACS were randomised to an 'immediate percutaneous coronary intervention (PCI)' strategy or a strategy of PCI on the 'next working day'. Radial access was predominantly used in this study population. The present subanalysis evaluated the occurrence of major bleeding complications and their association with mortality at 1 month.Patients were treated with a triple antiplatelet therapy using high loading and maintenance doses of clopidogrel and abciximab in 99% of patients receiving PCI. The trans-radial approach was used in the vast majority of patients (84%). During the first 30 days, major bleeding complications (STEEPLE definition) occurred in 5.4% of patients (n=19), with no difference between immediate and delayed intervention. The most common bleeding complications were occult bleeding (36.8% of bleeding, n=7/19) and overt gastrointestinal bleeding (21% of bleeding, n=4/19). Patients with major bleeding had a higher peak concentration of creatinine during hospitalisation (mean±SD, 170±169 vs 97±57 μmol/l; p=0.005) and a 1-month mortality of 26.3%, much higher than patients without bleeding (0.6%, p0.0001). Major bleeding was strongly associated with 30-day mortality (OR 50.3; 95% CI 10.1 to 249.7; p0.0001).Despite the predominant use of the radial approach, major bleeding (essentially occult and gastrointestinal) remains a common complication, which is highly associated with mortality in patients with NSTE-ACS treated with optimal antithrombotic therapy.

Objectives We sought to analyze the composition of coronary thrombus in vivo in ST-segment elevation myocardial infarction (STEMI) patients. Background The dynamic process of intracoronary thrombus formation in STEMI patients is poorly understood. Methods Intracoronary thrombi (n 45) were obtained by thromboaspiration in 288 consecutive STEMI patients presenting for primary percutaneous intervention, and analyzed using high-definition pictures taken with a scanning electron microscope. Plasma biomarkers (TnI, CRPus, IL-6, PAI-1, sCD40 ligand, and TNF-) and plasma fibrin clot viscoelastic properties were measured simultaneously on peripheral blood. Results Thrombi were mainly composed of fibrin (55.9 18%) with platelets (16.8 18%), erythrocytes (11.5 9%), cholesterol crystals (5.2 8.4%), and leukocytes (1.3 2.0%). The median ischemic time was 175 min (interquartile range: 140 to 297). Ischemic time impacted thrombi composition, resulting in a positive correlation with intracoronary thrombus fibrin content, r 0.38, p 0.01, and a negative correlation with platelet content, r 0.34, p 0.02. Thus, fibrin content increased with ischemic time, ranging from 48.4 21% ( 3h ) up to 66.9 9% ( 6h ) (p 0.02), whereas platelet content decreased from 24.9 23% ( 3h ) to 9.1 6% ( 6h ) (p 0.07). Soluble CD40 ligand was positively correlated to platelet content in the thrombus (r 0.40, p 0.02) and negatively correlated with fibrin content (r 0.36; p 0.04). Multivariate analysis indicated that ischemic time was the only predictor of thrombus composition, with a 2-fold increase of fibrin content per ischemic hour (adjusted odds ratio: 2.00 [95% confidence interval: 1.03 to 3.7]; p 0.01). Conclusions In acute STEMI, platelet and fibrin contents of the occlusive thrombus are highly dependent on ischemia time, which may have a direct impact on the efficacy of drugs or devices used for coronary reperfusion. (J Am Coll Cardiol 2011;57:1359‐67) © 2011 by the American College of Cardiology Foundation

Thienopyridines have become the cornerstone of treatment of percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y(12) inhibitors are more potent, more predictable and have a faster onset of action than clopidogrel, characteristics that make them particularly attractive for high-risk PCI. Four new P2Y(12) inhibitors have been tested each of them having particular individual properties. Prasugrel is an oral prodrug leading to irreversible blockade of the P2Y(12) receptor and is approved worldwide for ACS PCI. Ticagrelor is a direct-acting and reversible inhibitor of the P2Y(12) receptor with potentially more pleiotropic effects. Cangrelor is an intravenous direct and reversible inhibitor of the P2Y(12) receptor providing the highest level of inhibition and elinogrel is an intravenous and oral P2Y(12) antagonist with a direct and reversible action. Both prasugrel and ticagrelor, opposed to clopidogrel, have shown that stronger P2Y(12) inhibition led respectively to significant 19 % and 16 % relative risk reduction of a similar primary endpoint combining cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Both drugs showed a significant 0.6 % absolute excess of TIMI major bleeding not related to CABG surgery. The effect of these new compounds is prompt, predictable and powerful as compared to clopidogrel. Their net benefit is particularly marked in PCI for STEMI patients, in which there is no significant increase in major bleeding when compared with clopidogrel. However, because in clinical trials patients perceived to be at higher risk for bleeding usually are excluded, the risk of major and even fatal bleeding might even be higher in a "real-world" setting i.e. in the elderly patient with comorbidities.

Over the past decades, antiplatelet therapy has evolved from the relatively weak oral agent aspirin to additional oral and parenteral agents with greater antiplatelet activity. One example of a successful agent is the second-generation thienopyridine clopidogrel. Clopidogrel inhibits platelet P2Y12 receptors and given with aspirin, which inhibits cyclooxygenase-1 enzyme, composes the actual standard of care of dual antiplatelet therapy.1–3 Dual antiplatelet therapy is recommended by the American College of Cardiology/American Heart Association, American College of Chest Physicians, and the European Society of Cardiology (ESC) for patients undergoing percutaneous coronary intervention (PCI) and patients with ST-elevated myocardial infarction (STEMI) or unstable angina (UA)/non-STEMI (NSTEMI).4–10 A common point of emphasis in these guidelines is the recommendation to provide a clopidogrel loading dose (LD) before PCI, although uncertainty remains in these recommendations on the optimal dose and optimal timing of administration. Whereas the American College of Cardiology/American Heart Association UA/NSTEMI guidelines recommend a 300-mg clopidogrel LD, they acknowledge that although the supporting evidence is much weaker than that for a 300-mg LD, a higher dose of 600 or 900 mg may be more beneficial in some circumstances.8 The PCI guidelines recommend a 600-mg clopidogrel LD before or during the procedure.10 The ESC guidelines suggest that a 600-mg LD may be initiated immediately after the first medical contact for invasively managed patients with NSTEMI.5,6 Unfortunately, there are no clinical data and, therefore, no recommendation on the maintenance dose (MD) during the acute phase or chronic phase. The Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events/Optimal Antiplatelet Strategy for Interventions (CURRENT-OASIS 7) trial is the first large-scale, randomized trial to compare 2 strategies: high-dose clopidogrel (600-mg LD/150-mg MD) versus standard-dose clopidogrel (300-mg LD/75-mg MD) to assess the added benefit of a higher platelet …

SummaryIt was the objective of this study to assess the effect of the implementation of the smoke-free legislation on haemostasis and systemic inflammation in second-hand smoking (SHS)-exposed healthy volunteers. Fibrin-rich clot properties, platelet reactivity and inflammatory biomarkers were measured before and four months following the implementation of the smoke-free legislation in gender and age-matched healthy volunteers exposed (n=23, exposed) and unexposed (n=23, controls) to occupational SHS. The primary objective was to compare fibrin-rich clot stiffness before and after implementation of the smoke-free legislation. There was 40% reduction in fibrin-rich clot stiffness following the implementation of the smoke-free legislation in SHS-exposed volunteers (17 ± 7 vs. 10.6 ± 7 dynes/cm², before and after, respectively, p=0.001). These dramatic changes were associated with a 20% reduction in fibrin fiber density (p

Objectives: We evaluated the incidence, types, and prognostic impact of bleeding complications in a non-selected patient population with ongoing STEMI treated with aggressive antithrombotic treatment and routine radial primary PCI. Background: Bleeding complications remain frequent and deleterious in primary PCI through femoral approach. Methods: STEMI patients (n = 671) were evaluated for bleeding complications using a web-based registry (e-PARIS). In-hospital bleeding was adjudicated using the TIMI definition. Results: In this non-selected, high risk population, 6.1% had cardiogenic shock on admission, 3.9% out-of-hospital cardiac arrest. Radial access (88%) was the default strategy as was abciximab (78%). Clopidogrel loading dose ranged from 300 to 900 mg. Pre-hospital fibrinolysis was rare (7.1%). Hemodynamic support devices (IABP, ECMO, Tandem Heart) were needed in 7.0%. In-hospital TIMI Major and TIMI Major/minor bleedings occurred in 2.5 and 5.7% of the population, respectively. In-hospital and 1-year mortality rates were 5.5 and 8.2%, respectively. Patients with in-hospital TIMI Major/minor bleeding had a higher 1-year mortality rate (31.6% vs. 3.8%, P < 0.001). The most frequent bleeding site was gastro-intestinal. Radial access was a strong predictor of survival (OR 0.33; 95%CI 0.17–0.56; P = 0.002). Conclusions: In the setting of radial primary PCI, the rates and types of bleeding complications are somewhat different from those observed with femoral primary PCI. The gastro-intestinal tract has become the most frequent site of bleeding after radial primary PCI. The use of radial access appears independently associated with survival. © 2011 Wiley Periodicals, Inc

Aim We sought to determine the incidence and type of major bleeding in moderate-to-high risk acute coronary syndromes (ACS) treated with intense antiplatelet therapy and systematic invasive strategy using predominantly the radial approach. We also examined whether these bleedings has an impact on mortality after multivariable adjustment. Methods In the multicenter randomized ABOARD study, 352 patients with acute coronary syndromes without ST-segment elevation were randomized for a “primary PCI” strategy or a strategy of intervention deferred to the next working day. No difference was observed in clinical outcomes between the two groups. Major bleeding complications (STEEPLE definitions) were correlated to 1 month mortality. Results Patients were treated by intense antiplatelet therapy: with a mean 660 mg (±268) loading of clopidogrel and 111 mg (±40) maintenance dose while 99% of the PCI patients receive abciximab the radial approach was predominant (84%). During the first 30 days major bleeding complications occurred in 19 patients (5.4%) with transfusion in 16 patients (4.5%). Occurrence of major bleeding did not differ between immediate and delayed intervention. The most frequent overt bleeding complications were from the gastrointestinal tract. The composite of GI bleeding and occult bleeding (loss of Hb of >3 g/dL) represented n = 11 (57.9%) of all major bleeding complications. Major bleeding was associated with a significantly higher peak of creatinine during hospitalization 170.16 μmol/L ± 169.34 vs. 97.05 μmol/L ± 56.96 (p = 0.005) and a higher mortality rate 26.3% vs. 0.6%. After adjustment for all baseline characteristics, major bleeding was independently associated with an impressive increased hazard of death during the first 30 days (Odd ratio 75.7; 95% CI, 11.3 to 505.3; p Conclusion In a population of radial catheterization for NSTEACS, GI bleeding is the most frequent bleeding complication. Despite the reduction of access site bleeding, major bleeding still remains a major independent predictor of mortality.

We thank Drs. Giannopoulos and Deftereos for their excellent comments on the potential role of red blood cells (RBCs) as an explanation for the excess of risk due to RBC transfusion. We share their view on this point as data show an association between cell-free, hemoglobin-based blood substitutes

Summary Background It is unknown whether the efficacy and safety of drug-eluting stents (DES) apply in patients with chronic renal failure (CRF). Aims To compare DES with bare metal stents (BMS) for percutaneous coronary intervention (PCI) in CRF patients. Patients and methods Consecutive patients treated by PCI were allocated to four groups according to type of stent used (DES versus BMS) and creatinine clearance (CrCl). CRF was defined as CrCl less than 60 mL/minute. Cardiovascular death, major adverse cardiac events (MACE, defined as cardiovascular death, myocardial infarction, stroke and target lesion revascularization [TLR]), TLR and definite stent thrombosis (ST) were recorded at 1 year. Results We note that 1376 consecutive patients underwent PCI with stent within 18 months: 534 (39%) and 492 (36%) patients without CRF and 224 (16%) and 126 (9%) patients with CRF were treated with BMS and DES, respectively. In the entire cohort, patients treated with DES had a higher restenosis risk profile. BMS were predominantly (87%) used for ST-segment elevation myocardial infarction. At 1 year, 6.2% had cardiovascular death, 15.8% MACE, 7.3% TLR and 1.5% ST. Cardiovascular death and MACE occurred less frequently in DES groups. The TLR rate was not significantly different in the CRF groups (BMS 9.8% vs DES 7.1%; P = 0.44). No excess of ST was observed in the DES groups and use of DES was independently associated with absence of MACE and TLR. Conclusions In patients with CRF, DES appear to be at least as effective as BMS — despite a higher restenosis risk profile — with no excess of ST at 1 year.

Chronic kidney disease (CKD) is a serious condition associated with premature mortality, decreased quality of life, and increased health-care expenditures. The most recent data from the National Health and Nutrition Examination Survey estimated that the prevalence of CKD in the US population was 16.8% and had increased by 15.9% in comparison with that of the previous decade.1 These numbers are expected to rapidly increase with the aging of the population and furthermore with the epidemic of diabetes mellitus, a condition associated with a three-fold increase of the prevalence of CKD.2,3 Article see p 1056 CKD prevalence is twice as high in patients with cardiovascular disease, and recent registry data using the contemporary Modification of Diet in Renal Disease equation have reported a prevalence of moderate or severe CKD of 30.5% in ST elevation myocardial infarction4 and 42.9% in non-ST elevation myocardial infarction. This figure is much higher than what is usually reported in controlled trials where patients with CKD are often excluded, but similar to what has been observed in other registries.5 Figure. Hazard ratio for efficacy (95% confidence interval) evaluated as the composite end point of cardiovascular death, myocardial infarction, or stroke, in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE), Clopidogrel for Reduction of Events During Observation (CREDO), TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugre (TRITON) and PLATO trials according to renal function calculated with the Cockroft-Gault equation when not specified or the Modification of Diet in Renal Disease equation when indicated so. * indicates a significant relative risk reduction with the study criteria or a significant probability value for interaction between subgroups. NA indicates not available. Renal dysfunction is a powerful independent predictor of thrombotic and bleeding complications and, subsequently, of mortality. Worse clinical outcomes …

The purpose of this study was to perform a meta-analysis of randomized trials that compare new P2Y(12) inhibitors with clopidogrel to determine whether they improve clinical outcomes after percutaneous intervention (PCI).Ticlopidine/clopidogrel prevents major adverse cardiac events after PCI, but no trials have shown an effect on mortality. New P2Y(12) inhibitors are more potent and evaluated in PCI. Whether they decrease mortality after PCI compared with clopidogrel is unknown.MEDLINE and Cochrane Controlled Trials Register databases were searched from January 1980 through January 2010. Randomized, placebo-controlled trials that compared new P2Y(12) antagonists with clopidogrel in PCI were selected. Data from 8 studies were evaluated and analyses performed for all randomized patients, PCI patients (any PCI), and PCI for ST-segment elevation myocardial infarction (STEMI) patients. All-cause mortality was the primary efficacy end point. Thrombolysis In Myocardial Infarction major bleeding was the primary safety end point.A total of 48,599 patients were included with 94% of patients with acute coronary syndrome and 84% of patients undergoing PCI. New P2Y(12) inhibitors significantly decreased death (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.75 to 0.92, p0.001 for the whole cohort; OR: 0.85, 95% CI: 0.75 to 0.96, p = 0.008 for any PCI; and OR: 0.78, 95% CI: 0.66 to 0.92, p = 0.003 for PCI for STEMI). In PCI patients, new P2Y(12) inhibitors also significantly decreased major adverse cardiac events by 18% (p0.001) and stent thrombosis by 40% (p0.001). Although there was an increase in Thrombolysis In Myocardial Infarction major bleeding for any PCI (OR: 1.23, 95% CI: 1.04 to 1.46, p = 0.01), no difference was observed in PCI for STEMI (OR: 0.98, 95% CI: 0.85 to 1.13, p = 0.76), with similar outcomes in primary PCI for STEMI. Results were confirmed in sensitivity analyses that removed the largest study.New P2Y(12) inhibitors decrease mortality after PCI compared with clopidogrel. The risk/benefit ratio is particularly favorable in PCI for STEMI patients.

Background Upper Gastrointestinal Symtoms (UGS) is a reason for discontinuation in patients treated by Low Dose Aspirin (LDA). The nationwide UGLA survey was designed to evaluate the prevalence and the pattern of UGS in patients on LDA, to assess the independent correlates of UGS and finally to determine their impact on treatment compliance. Methods The UGLA survey was carried out on a representative sample of 10,000 subjects aged 50 or over. Prevalence and clinical impact of UGS related to LDA was appraised by standardised multi-choice questions. Results A total of 8106 propositus (8106/10,000) accepted to participate in the survey. Among them, 986 (12.2%) were treated with LDA. The prevalence of UGS was 15.4% in subjects on chronic LDA (152/986), 70% being gastroesophageal reflux (GER) (heartburn and/or regurgitation). UGS was reported to occur at least once a week in 60% of propositus (91/152) and daily life was reported to be moderately and severely impaired in 53% (81/152) and 20% (30/152) of them, respectively. UGS impacted compliance to treatment in 12% of propositus with UGS. A prior history of dyspeptic symptoms was predictive of LDA-related UGS (OR: 17.60; CI 95%: 11.52–26.88) whereas neither, gender nor aspirin dosage (ranging from 75 and 325mg) predicted the occurrence of UGS. Conclusions Fifteen percent of patients treated with LDA suffered UGS, mostly GER symptoms which had a negative impact on daily life in 3 out of 4 patients and on treatment compliance in 1 out of 8 patients.

AimIn STEMI, controversial data exist on the relative importance of patient-dependent time (Symptom-Onset (SO) to first medical contact (FMC)) and Transfer Time (TT=time from FMC to sheath insertion). We assessed the impact of TT on in-hospital (IH) mortality in a well organized urban network using Mobile Intensive Care Units (MICU).MethodsIn a web-based registry (e-PARIS), we evaluated delay in care of 705 consecutive STEMI patients transferred to the Pitié-Salpêtrière cath-lab for primary PCI.ResultsPopulation was 63±14 y/o, 75.6% were male, 46.9% had anterior MI, 16.7% were in Killip class 2, and 3.8% had out-of-hospital cardiac arrest. Abciximab was used in 82.4%, radial approach in 87.7% and stenting in 89.7% of patients. Median time (IQR) from SO to FMC was 110 (248) min (102 (190) min when FMC was MICU and 160 (381) min when FMC was a referring hospital, p2 hours of SO) (fig). After adjustment for baseline characteristics, TT was not associated with mortality anymore suggesting that the sicker patients had the longest TT.ConclusionsThe association between TT and early mortality is strongly dependent on patients’ characteristics and time to presentation. After adjustment for these parameters, TT does not appear to be a major contributor of IH mortality in a well organized urban network for primary PCI. Improving time-to-first medical contact may be more critical.

Background Gamma’ fibrinogen (γ’Fg) is a Fg isoform that constitutes about 15% of total plasma Fg and contains an additional binding site for factor XIII and for IIa forming clots that are resistant to fibrinolysis in vitro. Little is known about γ’Fg in the pathophysiology of Acute Coronary Syndrome (ACS) patients. Aim To compare γ’Fg level and the relation with fibrin clot physical properties in a young post-MI patients matched for age and gender and age with healthy controls. Method γ’Fg was measured in duplicates in 260 young post-MI patients and n=260 controls. Maximum fibrin elastic modulus (EM in dyne/cm2), a measure of clot stiffness (G’) and Clot Lysis Time (CLT in sec) a measure of fibrinolysis rate were measured in all subject. Results Patients produced stiffer plasma fibrin with increased EM (24.4±15.9 vs 13.5±5.9 kdynes/cm2 ; p Conclusion γ’Fg concentration was found to be significantly higher in young post-MI patients as compared to healthy controls matched for age and gender and may account for the great differences in fibrin clot physical properties between patients and controls, an independent correlate of premature coronary artery disease. Download : Download full-size image

BackgroundThe *2 variant of the CYP2C19 gene encodes a defective enzyme that likely fails to adequately convert clopidogrel to its active metabolite, leading to diminished cardiovascular protection.ObjectivesWe performed a meta-analysis of trials that determined the CYP2C19*2 genetic variant in patients exposed to clopidogrel therapy after stent implantation. The primary objective was to evaluate whether carriage of the CYP2C19*2 was associated with the occurrence of stent thrombosis, recurrent myocardial infarction and cardiovascular death.Methods and resultsEight trials (9427 patients) with data available data on death, recurrent myocardial infarction, stent thrombosis and any ischemic events were selected. The odds ratio (OR) as the parameter of efficacy with a fixed effect model was used. Carriers of the genetic variant associated with a loss-of-function of the CYP2C19 enzyme (28%, n=2674) displayed a 30% increase in the risk in any ischemic events compared to non carriers (10.4% vs 8.3%) (OR, 1.31; 95% CI, 1.12-1.53; p

The aim of this study was to assess the association between the loss-of-function cytochrome P450 2C19 (CYP2C19)*2 variant (10 studies, 11,959 patients) or the use of proton pump inhibitors (PPIs) (13 studies, 48,674 patients) and ischemic outcomes (major adverse cardiovascular events [MACE]) in patients treated with clopidogrel.In clopidogrel-treated patients, increased cardiovascular risk has been identified with the loss-of-function CYP2C19*2 allele or the use of PPIs, some of them CYP2C19 inhibitors. To further estimate the effect of a reduction in activity of this enzyme, the authors performed a meta-analysis of the studies available.The meta-analysis was performed on 23 studies using the odds ratio (OR) as the parameter of efficacy, with a fixed-effect model. The end points were MACE, mortality, or stent thrombosis.Of the 11,959 patients, carriers of the loss-of-function CYP2C19*2 allele (28% [n = 3,418]) displayed a 30% increase in the risk for MACE compared with noncarriers (9.7% vs. 7.8%; OR: 1.29; 95% confidence interval [CI]: 1.12 to 1.49; p0.001). This single gene variant (CYP2C19*2) was also associated with an excess of mortality (1.8% vs. 1.0%; OR: 1.79; 95% CI: 1.10 to 2.91; p = 0.019; n = 6,225) and of stent thrombosis (2.9% vs. 0.9%; OR: 3.45; 95% CI: 2.14 to 5.57; p0.001; n = 4,905). This increased risk was apparent in both heterozygotes and homozygotes and was independent of the baseline cardiovascular risk. PPI users (42% [n = 19,614]) displayed increased risk for MACE (21.8% vs. 16.7%; OR: 1.41; 95% CI: 1.34 to 1.48; p0.001) and mortality (12.7% vs. 7.4%; OR: 1.18; 95% CI: 1.07 to 1.30; p0.001; n = 23,977) compared with nonusers. The impact of PPI use was, however, significantly influenced by baseline cardiovascular risk, being significant only in high-risk patients.In this global meta-analysis, reduced CYP2C19 function appears to expose clopidogrel-treated patients to excess cardiovascular risk and mortality. Conflicting results among studies may be explained by differences in types and/or levels of risk of patients.

International audience; CONTEXT: International guidelines recommend an early invasive strategy for patients with high-risk acute coronary syndromes without ST-segment elevation, but the optimal timing of intervention is uncertain. OBJECTIVE: To determine whether immediate intervention on admission can result in a reduction of myocardial infarction compared with a delayed intervention. DESIGN, SETTING, AND PATIENTS: The Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention (ABOARD) study, a randomized clinical trial that assigned, from August 2006 through September 2008 at 13 centers in France, 352 patients with acute coronary syndromes without ST-segment elevation and a Thrombolysis in Myocardial Infarction (TIMI) score of 3 or more to receive intervention either immediately or on the next working day (between 8 and 60 hours after enrollment). MAIN OUTCOME MEASURES: The primary end point was the peak troponin value during hospitalization; the key secondary end point was the composite of death, myocardial infarction, or urgent revascularization at 1-month follow-up. RESULTS: Time from randomization to sheath insertion was 70 minutes with immediate intervention vs 21 hours with delayed intervention. The primary end point did not differ between the 2 strategies (median [interquartile range] troponin I value, 2.1 [0.3-7.1] ng/mL vs 1.7 [0.3-7.2] ng/mL in the immediate and delayed intervention groups, respectively; P = .70). The key secondary end point was observed in 13.7% (95% confidence interval, 8.6%-18.8%) of the group assigned to receive immediate intervention and 10.2% (95% confidence interval, 5.7%-14.6%) of the group assigned to receive delayed intervention (P = .31). The other end points, as well as major bleeding, did not differ between the 2 strategies. CONCLUSION: In patients with acute coronary syndromes without ST-segment elevation, a strategy of immediate intervention compared with a strategy of intervention deferred to the next working day (mean, 21 hours) did not result in a difference in myocardial infarction as defined by peak troponin level. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00442949.

ObjectivesThis study evaluated the ability of the bedside test Hemochron Jr. Hemonox (International Technidyne Corporation, Edison, New Jersey) to identify patients with insufficient anti-Xa activity level in the catheterization laboratory.BackgroundInadequate anticoagulation in patients undergoing percutaneous coronary intervention (PCI) is associated with increased periprocedural ischemic events.MethodsIn 296 unselected patients undergoing catheterization and/or PCI, whole blood Hemonox clotting time (CT) and activated partial thromboplastin time (aPTT) were measured at baseline (T1) and 10 min after the intravenous administration of enoxaparin (T2) in patients receiving additional enoxaparin and compared with plasma chromogenic anti-Xa activity level.ResultsMedian values were 0.1 IU/ml (interquartile range [IQR]: 0.1 to 0.1 IU/ml) and 0.87 IU/ml (IQR: 0.74 to 1.03 IU/ml) for anti-Xa; 74 s (IQR: 70 to 81 s) and 143 s (IQR: 114 to 206 s) for Hemonox CT; and 44 s (IQR: 39 to 50 s) and 72 s (IQR: 58 to 93 s) for aPTT at T1 and T2, respectively. When using Hemonox CT to discriminate patients with anti-Xa level

Clopidogrel and low-dose aspirin have become the mainstay oral antiplatelet regimen to prevent recurrent ischaemic events after acute coronary syndromes or stent placement. The frequent genetic functional variant 681 GA (*2) of cytochrome P450 2C19 (CYP2C19) is an important contributor to the wide variability between individuals of the antiplatelet effect of clopidogrel. We assessed whether the CYP2C19*2 polymorphism affected long-term prognosis of patients who were chronically treated with clopidogrel.Between April 1, 1996, and April 1, 2008, 259 young patients (aged45 years) who survived a first myocardial infarction and were exposed to clopidogrel treatment for at least a month, were enrolled in a multicentre registry and underwent CYP2C19*2 determination. The primary endpoint was a composite of death, myocardial infarction, and urgent coronary revascularisation occurring during exposure to clopidogrel. Follow-up was every 6 months. The key secondary endpoint was stent thrombosis proven by angiography.Median clopidogrel exposure time was 1.07 years (IQR 0.28-3.0). Baseline characteristics were balanced between carriers (heterozygous *1/*2, n=64; homozygous *2/*2, n=9) and non-carriers (n=186) of CYP2C19*2 variant. The primary endpoint occurred more frequently in carriers than in non-carriers (15 vs 11 events; hazard ratio [HR] 3.69 [95% CI 1.69-8.05], p=0.0005), as did stent thrombosis (eight vs four events; HR 6.02 [1.81-20.04], p=0.0009). The detrimental effect of the CYP2C19*2 genetic variant persisted from 6 months after clopidogrel initiation up to the end of follow-up (HR 3.00 [1.27-7.10], p=0.009). After multivariable analysis, the CYP2C19*2 genetic variant was the only independent predictor of cardiovascular events (HR 4.04 [1.81-9.02], p=0.0006).The CYP2C19*2 genetic variant is a major determinant of prognosis in young patients who are receiving clopidogrel treatment after myocardial infarction.

High on-treatment platelet reactivity is an independent risk factor of major adverse cardiovascular events following percutaneous coronary intervention or Acute Coronary Syndrome (ACS). HIV-infected patients have a higher risk of recurrent events after ACS than HIV uninfected patients. We

ACTION Study Group; International audience; We thank Dr Gonçalves and Dr Araújo for their comments. We agree on several points that emphasize the messages that are delivered in our editorial. [...]

Objective— Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting. Methods and Results— Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post–myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls ( P P =0.002), made of numerous ( P =0.002) and shorter fibers ( P =0.04), and lysed at a slower rate than that of controls ( P =0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis. Conclusions— This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. The determinants of this particular phenotype warrant further investigation.

Background Recent clinical studies suggest that low molecular weight heparin (LMWH) could be an effective and safe alternative to unfractionated heparin (UFH) for patients with acute myocardial infarction (AMI). Aims To assess the impact of the choice of anticoagulant (LMWV vs. UFH) on bleeding, the need for blood transfusion and three-year clinical outcomes in patients with AMI from the FAST-MI registry. Methods FAST-MI is a nationwide registry carried out in France over a 1-month period in 2005, including consecutive patients with AMI admitted to intensive care unit Results 2854 patients treated with heparins were included. The risk of major bleeding or transfusion (3.0% vs. 7.0%) and in-hospital death (3.2% vs 9.2%) was lower with LMWH compared with UFH, a difference that persisted after multivariate adjustment (OR=0.51, 95% CI: 0.34-0.76 and OR=0.53, 95% CI: 0.37-0.76, respectively). Three-year survival and stroke and reinfarction-free survival were also higher with LMWH compared with UFH (adjusted HR =0.73, 95% CI: 0.61-0.86 and HR =0.73, 95% CI: 0.62-0.85, respectively). In two cohorts of patients matched on a propensity score for getting LMWH and with similar baseline characteristics (834 patients per group), major bleeding and transfusion were lower while three-year survival was signicantly higher in patients receiving LMWH. Conclusion The present data suggest that the use of LMWH in AMI patients may have a better benefit/risk profile than UFH with in terms of bleeding, need for transfusion, and long term survival.