Prognostic value of longitudinal strain and ejection fraction in Friedreich's ataxia.

BACKGROUND: Friedreich's ataxia (FA) is a rare autosomal recessive mitochondrial disease most commonly due to a triplet repeat expansion guanine-adenine-adenine (GAA) in the FXN gene. Cardiac disease is the major cause of death, patients with reduced left ventricular ejection fraction (LVEF) having the worse prognosis. Longitudinal strain (LS) appeared to be a better predictor of outcome than LVEF in different diseases. We compared the prognostic value of LS measured from the 4 chambers view to LVEF. METHODS: From 2003 to 2017 consecutive patients with FA were included and LS analysis was retrospectively performed. RESULTS: We studied 140 patients, with a median age of 34 (26-41) years (Q1-Q3) with age at onset of 14 (11-19) years and GAA repeats on the shorter allele of 600 (467-783) pb. Mean LS was 19.9 ± 5.0% and LVEF 64 ± 8%. After a mean follow-up of 7.4 ± 3.9 years, 14 patients died. In univariate Cox analysis, all-cause mortality was associated with: LS (HR 0.83; 95%CI, 0.75-0.91, p = 0.0002), LVEF (HR 0.30; 95%CI, 0.19-0.49, p < 0.0001), GAA repeats on the shorter allele (HR 1.29; 95%CI, 1.10-1.51, p = 0.002), age at onset (HR 0.87; 95%CI, 0.77-0.98, p = 0.018), LVSystolic Diameter (HR 1.17; 95%CI, 1.09-1.26, p < 0.0001), LVMass index (HR 1.02; 95%CI, 1.00-1.04, p = 0.027), and LVDiastolic Diameter (HR1.12; 95%CI, 1.01-1.23, p = 0.028). In multivariate analysis, LVEF was the only independent predictor of mortality (HR 0.41; 95%CI, 0.23-0.74, p = 0.0029). CONCLUSION: In FA, LS was not an independent predictor of mortality, LVEF remained the only independent predictor in the present study.

Unusual arterial thrombotic events in Covid-19 patients.

INTRODUCTION: COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated. OBJECTIVES: To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event. MATERIAL AND METHODS: We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis. RESULTS: From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy. CONCLUSION: Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated.

Clinical characteristics and outcomes of COMPASS eligible patients in France. An analysis from the REACH Registry.

BACKGROUND: Following the publication of the COMPASS trial, the European Medicines Agency has approved a regimen of combination of rivaroxaban 2.5mg twice daily and a daily dose of 75-100mg acetylsalicylic acid (ASA) for patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events. However, the applicability of such a therapeutic strategy in France is currently unknown. AIMS: To describe the proportion of patients eligible to COMPASS in France, their baseline clinical characteristics and the rate of major adverse cardiovascular events, using the REACH registry. METHODS: From the the REduction of Atherothrombosis for Continued Health (REACH) registry database, a large international registry of patients with, or at risk, of atherothrombosis, we analyzed patients included in France with either established CAD and/or PAD and fulfilling the inclusion and exclusion criteria of the COMPASS trial. The ischemic outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke, and serious bleeding were defined as haemorrhagic stroke or bleeding leading to hospitalization or transfusion. RESULTS: Among more than 65000 patients enrolled in REACH, 2.012 patients were evaluable and enrolled in France. Among them, 1194 patients (59.3%) were eligible to COMPASS. The main reasons for exclusion of the COMPASS trial, were high bleeding risk (59.1%), anticoagulant use (43.4%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI (24.7%). In the "COMPASS eligible population", the rate of MACE (CV, MI and stroke) at 4 years follow-up was 13.4% [11.3-15.8], and serious bleeding was 2.5% at 4 years [1.6-3.4]. Patients with polyvascular disease (n=219) had the highest rate of MACE, compared with patients with CAD only and PAD only (19.1% [13.9-26.1] vs. 11.6% [9.1-14.8] vs 13.2% [9.2-18.8], P<0.0001, respectively). CONCLUSION: The COMPASS therapeutic strategy in France appears to be applicable to more than half of CAD or PAD patients. This population appears at high residual risk of atherothrombotic events, and patients with polyvascular disease experienced the highest rate of events.

High cardiovascular event rates in patients with asymptomatic carotid stenosis: the REACH Registry.

BACKGROUND AND PURPOSE: Data on current cardiovascular event rates in patients with asymptomatic carotid artery stenosis (ACAS) are sparse. We compared the 1-year outcomes of patients with ACAS > or =70% versus patients without ACAS in an international, prospective cohort of outpatients with or at risk of atherothrombosis. METHODS: The Reduction of Atherothrombosis for Continued Health Registry enrolled patients with either > or =3 atherothrombotic risk factors or established atherothrombotic disease. We investigated the 1-year follow-up data of patients for whom physicians reported presence/absence of ACAS at the time of inclusion. RESULTS: Compared with patients without ACAS (n = 30 329), patients with ACAS (n = 3164) had higher age- and sex-adjusted 1-year rates of transient ischaemic attack (3.51% vs. 1.61%, P < 0.0001), non-fatal stroke (2.65% vs. 1.75%, P = 0.0009), fatal stroke (0.49% vs. 0.26%, P = 0.04), cardiovascular death (2.29% vs. 1.52%, P = 0.002), the composite end-point cardiovascular death/myocardial infarction/stroke (6.03% vs. 4.29%, P < 0.0001) and bleeding events (1.41% vs. 0.81%, P = 0.002). In patients with ACAS, Cox regression analyses identified history of cerebrovascular ischaemic events as most important predictor of future stroke (HR 3.21, 95% CI 1.82-5.65, P < 0.0001). CONCLUSION: Asymptomatic carotid artery stenosis was associated with high 1-year rates of cardiovascular and cerebrovascular ischaemic events. Stroke was powerfully predicted by prior cerebrovascular ischaemic events.

P2Y12 inhibitors: thienopyridines and direct oral inhibitors.

The P2Y12 receptor has proven to be a key target in the prevention of complications associated with atherosclerotic vascular disease especially in the context of acute coronary syndrome and percutaneous coronary intervention in addition to aspirin. Three generations of thienopyridines, ticlopidine, clopidogrel, and prasugrel have proven efficacy in the prevention of ischemic vascular events but with increased bleeding. The concept of individualized tailored therapy has recently emerged with the discovery of the diminished effect of some thienopyridine among carriers of the loss-of-function cytochrome (CYP) P4502C19*2 variant. Non-thienopyridine P2Y12 antagonists have also recently demonstrated that these benefits are not limited to one class of agents or may be generalizable to reversible antagonists of this receptor. Future rational use of these agents will require attention to disease and patient features to strike the optimal balance of benefit to risk.

Altered fibrin architecture is associated with hypofibrinolysis and premature coronary atherothrombosis.

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<0.05). Fibrin of young CAD patients was stiffer (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.

[Management coronary syndrome in the acute phase]. / Prise en charge du syndrome coronaire aigu à la phase aiguë.

The clinical benefit of the combination of aspirin plus clopidogrel over aspirin alone to prevent recurrent events after acute coronary syndrome is obviously a key step of the past few years in the management of coronary artery disease. The extended benefit of this combination among patients undergoing stent implantation is another key message for clinician. The consistent benefit of the dual oral antiplatelet therapy in all clinical trials is reassuring for clinicians. However, all well designed clinical trials generate new hypothesis and unsolved clinical issues. The loading dose of clopidogrel and whether we should monitor the biological response to clopidogrel in order to improve its clinical benefit are the next clinical challenges for clinicians dealing with acute coronary syndromes. Providing adequate answers to these relevant clinical issues should improve the clinical benefit of clopidogrel. All these important points are discussed in the following manuscript.

[Treatment of intracoronary thrombus in the catheterisation laboratory in acute coronary syndrome patients]. / Traitement du thrombus dans les syndromes coronaires aigus en salle de cardiologie interventionnelle.

Treatment of intracoronary thrombus is well documented. Three situations should be differentiated Primary percutaneous coronary intervention for early STEMI presenters is the most frequent one. Glycoprotein IIb/IIIa inhibitors are the gold standard antithrombotic treatment with a clear mortality benefit with abciximab. Thrombectomy with simple to use devices is another attractive option for interventionalists, although there is no clear established clinical benefit. Rescue PCI following failed thrombolysis is a more complicated situation given the underlying bleeding risk that is difficult to evaluate. The second situation is when a thrombus appears during an elective PCI. Although much less frequent than primary PCI, it is more often related to a lack of identification of the risk, to an inappropriate choice of the materials or to a non-optimal upstream antithrombotic treatment. A careful identification of all potential relevant causes is the key point of the management strategy. Post-PCI rethrombosis is the third situation and probably the less frequent. However, it is the most difficult to deal with.

[Fibreoptic bronchoscopy and anti-platelet agents: a risk-benefit analysis]. / Bronchoscopie souple et antiagrégants plaquettaires: analyse du rapport bénéfices-risques.

INTRODUCTION: Respiratory physicians are confronted increasingly often by patients, in whom a fibreoptic bronchoscopy (FB) is planned, who are taking anti-platelet agents (APAs) prescribed by their cardiologist. It is necessary therefore to weigh the indications for bronchoscopy and the subsequent benefits against the risks, not only of haemorrhage, but of thrombosis if the APAs are withdrawn. METHODS/RESULTS: In the absence of agreed guidelines on the subject this article reviews the literature and reports the results of a survey conducted among 138 members of the French Respiratory Endoscopy Group. Five questions were considered: 1) what is the risk of haemorrhage during the procedure? 2) what are the pharmacological characteristics of current APAs? 3) what is the risk of thrombosis on withdrawal of APAs? 4) what are the circumstances in which the FB may be delayed? 5) what should be the therapeutic strategy if the APAs are withdrawn? CONCLUSIONS: While awaiting clinical studies that will allow a better understanding of these questions, and the subsequent publication of practice guidelines, it is crucial that respiratory physicians are aware of the need, prior to FB, to inquire routinely about treatment with APAs, to identify the indication, and never to interrupt such treatment without consulting the prescriber.

[Coronary thrombosis: Physiopathology and treatment in the era of tailored medicine]. / Thrombose coronaire : physiopathologie et traitement à l'ère de la médecine personnalisée.

Coronary thrombosis remains the leading cause for cardiovascular death in France. Great advances have been made in the knowledge of the basic mechanism involved in coronary thrombogenesis and in antithrombotic treatments. They have led to substantial survival benefit after myocardial infarction and enabled development of tailored therapeutic strategies, especially for high-risk patients. Direct oral anticoagulants have now entered the game for secondary prevention after coronary thrombosis.

A structural and dynamic investigation of the facilitating effect of glycoprotein IIb/IIIa inhibitors in dissolving platelet-rich clots.

Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors were shown recently to facilitate the rate and the extent of pharmacological thrombolysis. However, their synergistic potential with rtPA in dissolving thrombotic vaso-occlusions is not fully understood. We have therefore developed a dynamic and structural approach for analysis of fibrinolysis to assess the inhibiting effect of platelets and the facilitating effect of GPIIb/IIIa inhibitors in dissolving platelet-rich clots (PRCs). Fluorescent rtPA was used to study the architecture of PRCs, to follow the progression of the rtPA binding front, and to measure the lysis-front velocity using confocal microscopy. Fibrinolysis resistance of PRCs was related to a reduction of both rtPA binding and lysis-front velocities of platelet-rich areas compared with platelet-poor areas (2.4 +/- 0.2 versus 3.5 +/- 0.4 microm/min for rtPA binding velocity, P=0.04, and 1.2 +/- 0.6 versus 2.8 +/- 0.2 microm/min for lysis-front velocity, P=0.008, in platelet-rich and platelet-poor areas, respectively). Fibrinolysis appeared heterogeneous, leaving platelet-rich areas un-lysed. Adding pharmacological concentrations of abciximab (0.068 micromol/L) or eptifibatide (1 micromol/L) before clotting decreased the average surface of platelet-rich areas by 64% (P=0.0005) and 72% (P=0.0007), respectively. The resulting equalization of rtPA binding rate and rtPA binding-front velocity between platelet-rich and platelet-poor areas led to a 3-fold increase of the lysis-front velocity in platelet-rich areas of either abciximab-PRC (P=0.006) or eptifibatide-PRC (P=0.03). The overall lysis rate of treated-PRC was increased by 74% compared with control-PRC (P<0.01). These results demonstrate that fibrinolysis resistance of PRCs is related primarily to the heterogeneity in the clot structure between platelet-rich and platelet-poor areas. GP IIb/IIIa inhibitors facilitate the rate and the extent of fibrinolysis by improving rtPA binding velocity and, subsequently, the lysis rate in platelet-rich areas. These findings provide new insights on the synergistic potential of GP IIb/IIIa inhibitors and fibrinolytic agents.

[Present and future developments of antithrombotic agents]. / Développements actuels et futurs des antithrombotiques.

The search for the optimal antithrombotic efficacy to bleeding risk ratio in interventional cardiology has promoted the development of new antithrombotics and to the elaboration of new association strategies. The relatively modest and inconstant antiaggregant effect of 300 mg of clopidogrel has led to the use of higher dosages of 600 mg or 900 mg. The improved biological effects justify clinical evaluation on a larger scale. While waiting for the results of the CHARISMA trial, several studies seem to demonstrate the benefits of long-term administration. New thienopyridines, the leader of which is prasugrel, have powerful biological effects and have already been assessed in larger clinical trials. The anti GPIIb/IIIa molecules, the indications of which have been recently redefined, feature in new administration strategies under evaluation. The use of direct or indirect thrombin antagonists during invasive procedures remains necessary and several molecules are candidates for replacing unfractionated heparin, with a more predictable activity. Low molecule weight heparins have been shown to be easier to use compared with unfractionated heparin. Synthetic factor Xa inhibitors are at an early stage of development. Of the direct thrombin antagonists, bivalirudine provides an improved benefit/risk ratio and is a new option in the catheter laboratory.

[The value of active stents for coronary angioplasty in patients with chronic renal failure]. / Intérêt du stent actif dans l'angioplastie coronaire chez l'insuffisant rénal chronique.

UNLABELLED: The risk of intra-stent restenosis has diminished considerably with the advent of endoprostheses which actively release sirolimus or paclitaxel. Patients with chronic renal failure constitute a high cardiovascular risk population, in whom the incidence of coronary heart disease is particularly high, representing one of the principal causes of death. The aim of this study, which included 152 patients, was to quantify the value of active stents for coronary angioplasty in patients with chronic renal failure. Thirty eight patients with chronic renal failure who underwent angioplasty with active stents were matched for age, sex and the presence of diabetes with 3 other groups of patients: one group with active stents but without renal failure, one group with inactive stents and no renal failure, and one group with inactive stents and chronic renal failure. The average follow up was 16 +/- 5 months. The acute stent thrombosis rate (2%) was not elevated in cases of renal failure nor after active stent implantation. Chronic renal failure significantly increased the mortality rate 16 months after angioplasty, whichever type of stent was used: 8 versus 2% deaths in patients with an inactive stent (p = 0.001). In renal failure, the risk of death was lower with an active stent (8 vs 26% with an inactive stent, p<0.05). Similarly, there was a non-significant trend towards a lower risk of death and/or infarction in renal failure after active stents (8 vs 21% with an inactive stent, NS). CONCLUSIONS: In this study, coronary angioplasty with an active stent in patients with chronic renal failure was associated with a lower mortality rate compared with inactive stents, with no increase in the risk of acute thrombosis.

Exome sequencing of extreme clopidogrel response phenotypes identifies B4GALT2 as a determinant of on-treatment platelet reactivity.

Interindividual variability in platelet aggregation is common among patients treated with clopidogrel and both high on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, patients with coronary artery disease (CAD) with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n = 636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRUs; P = 0.0077) and residual platelet aggregation (P = 0.0008) compared with noncarriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (P = 0.0298) and replication (n = 160; PRU: P = 0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion.

Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis.

BACKGROUND: The benefit of primary percutaneous coronary intervention (PCI) over thrombolysis has been clearly demonstrated in acute myocardial infarction (AMI). However, the best therapeutic strategy for a patient with AMI presenting to acute care services without catheterization facilities remains under debate. Our objective was to gather all available information from clinical trials comparing transfer of patients experiencing AMI for angioplasty versus immediate thrombolysis. METHODS AND RESULTS: We performed a meta-analysis of all data available from published randomized trials and from presentations in scientific sessions of major cardiology congresses comparing the 2 strategies. The primary end point was the combined criteria (CC) of death/reinfarction/stroke as defined in each trial. Relative risk (RR) evaluated the treatment effect. We identified 6 clinical trials including 3750 patients. Transfer time was always <3 hours. The CC was significantly reduced by 42% (95% confidence interval [CI] 29% to 53%, P<0.001) in the group transferred for primary PCI compared with the group receiving on-site thrombolysis. When CC parameters were considered separately, reinfarction was significantly reduced by 68% (95% CI, 34% to 84%; P<0.001) and stroke by 56% (95% CI, -15% to 77%; P=0.015). There was a trend toward reduction in all-cause mortality of 19% (95% CI, -3% to 36%; P=0.08) with transfer for PCI. CONCLUSIONS: Even when transfer to an angioplasty center is necessary, primary PCI remains superior to immediate thrombolysis. Organization of ambulance systems, prehospital management, and adequate PCI capacity appear now to be the key issues in providing reperfusion therapy for AMI.

Low molecular weight heparin after mechanical heart valve replacement.

BACKGROUND: Patients with mechanical heart valves require life-long anticoagulation. We report here the first large and comparative series of consecutive patients anticoagulated with low molecular weight heparin (LMWH) after mechanical heart valve replacement. METHODS AND RESULTS: In this comparative, nonrandomized study, 208 consecutive patients who underwent a single or double heart valve replacement with mechanical prostheses were anticoagulated subcutaneously with unfractionated heparin (UH) in the first period (n=106) and LMWH in the second phase (n=102) of the study. Baseline characteristics were similar in the 2 groups. The mean durations of UH and LMWH treatments were 13.6+/-0.5 and 14.1+/-0.6 days, respectively (not significant). On the second day of treatment, 87% of patients treated with LMWH had an anti-Xa activity within the range of efficacy (0.5 to 1 IU/mL), but only 9% of UH-treated patients had an activated partial-thromboplastin time value within the therapeutic range (1.5 to 2.5 times control, P<0.0001 between the 2 groups). On the last day of prescription, all LMWH-treated patients had anti-Xa activity above 0.5 IU/mL, but 19% were above 1 IU/mL. In the UH group, 27% of patients had an activated partial-thromboplastin time above 1.5 times control, but 62% were overanticoagulated. Two major bleedings occurred in each group, and one stroke occurred in the UH group. CONCLUSIONS: In this first comparative study, anticoagulation with LMWHs after mechanical heart valve replacement appears feasible, provides adequate biological anticoagulation, and compares favorably with UH anticoagulation. Randomized studies are now needed to further evaluate this new therapeutic approach.

Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris.

BACKGROUND: Subcutaneous low-molecular-weight (LMW) heparins can effectively replace unfractionated heparin in patients with unstable angina or non-Q-wave myocardial infarction. However, the optimal anticoagulation strategy for these patients when they require cardiac catheterization is still unclear. Therefore, we evaluated a new and simple strategy of anticoagulation in these patients. METHODS AND RESULTS: A total of 451 consecutive patients with unstable angina/non-Q-wave myocardial infarction were treated for at least 48 hours with subcutaneous injections of enoxaparin (1 mg [100 IU]/kg every 12 hours, cycled at 6 AM and 6 PM). Of this unselected population, 293 patients (65%) underwent a coronary angiography within 8 hours of the morning LMW heparin injection, followed by immediate percutaneous coronary intervention (PCI) in 132 patients (28%). PCI was performed without any additional bolus of unfractionated/LMW heparin and without coagulation monitoring. Anti-Xa activity at the time of catheterization was 0.98+/-0.03 IU/mL, was >0.5 IU/mL in 97.6% of patients, and did not relate to the LMW heparin injection-to-catheterization time. There were no in-hospital abrupt closures or urgent revascularizations after PCI. The death/myocardial infarction rate at 30 days was 3.0% in the PCI group (n=132) but 6.2% in the whole population (n=451) and 10.8% in the patients not undergoing catheterization (n=158). The 30-day major bleeding rate was 0.8% in the PCI group, which was comparable to that of patients without catheterization (1.3%). CONCLUSIONS: PCI within 8 hours of the last enoxaparin subcutaneous injection seems to be safe and effective. The safety of subcutaneous LMW heparin in combination with platelet glycoprotein IIb/IIIa blockade awaits further study.

Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes.

BACKGROUND: Oral antiplatelet agents (OAAs) can prevent further vascular events in cardiovascular disease. How prior use or recent discontinuation of OAA affects clinical presentation of acute coronary syndromes (ACS) and clinical outcomes (death, myocardial infarction [MI]) is unclear. METHODS AND RESULTS: We studied and followed up for up to 30 days a cohort of 1358 consecutive patients admitted for a suspected ACS; of these, 930 were nonusers, 355 were prior users of OAA, and 73 had recently withdrawn OAA. Nonusers were at lower risk, more frequently presented with ST-elevation MI on admission, and more frequently had Q-wave MI at discharge than prior users (36.6% versus 17.5%, P<0.001; and 47.8% versus 28.2%, P<0.001, respectively). However, there was no difference regarding the incidence of death or MI at 30 days between nonusers and prior users (10.3% versus 12.4%, P=NS). In addition, prior users experienced more major bleeds within 30 days compared with nonusers (3.4% versus 1.4%, respectively; P=0.04). Recent withdrawers were admitted on average 11.9+/-0.8 days after OAA withdrawal. Interruption was primarily a physician decision for scheduled surgery (n=47 of 73). Despite a similar cardiovascular risk profile, recent withdrawers had higher 30-day rates of death or MI (21.9% versus 12.4%, P=0.04) and bleedings (13.7% versus 5.9%, P=0.03) than prior users. After multivariate analysis, OAA withdrawal was found to be an independent predictor of both mortality and bleedings at 30 days. CONCLUSIONS: Among ACS patients, prior users represent a higher-risk population and present more frequently with non-ST-elevation ACS than nonusers. Although patients with a recent interruption of OAA resemble those chronically treated by OAA, they display worse clinical outcomes.

Anti-Xa activity relates to survival and efficacy in unselected acute coronary syndrome patients treated with enoxaparin.

BACKGROUND: Low-molecular-weight heparin (LMWH) is recommended in the treatment of unstable angina (UA)/non-ST-segment-elevation myocardial infarction (NSTEMI), but no relationship has ever been shown between anticoagulation levels obtained with LMWH treatment and clinical outcomes. METHODS AND RESULTS: In all, 803 consecutive patients with UA/NSTEMI were treated with subcutaneous enoxaparin and were followed up for 30 days. The recommended dose of enoxaparin of 1 mg/kg BID was used throughout the population except when physicians decided on dose reduction because of a history of a recent bleeding event or because of a high bleeding risk. Anti-factor Xa activity was >0.5 IU/mL in 93% of patients; subtherapeutic anti-Xa levels (<0.5 IU/mL) were associated with lower doses of enoxaparin. The 30-day mortality rate was significantly associated with low anti-Xa levels (<0.5 IU/mL), with a >3-fold increase in mortality compared with the patients with anti-Xa levels in the target range of 0.5 to 1.2 IU/mL (P=0.004). Multivariate analysis revealed low anti-Xa activity as an independent predictor of 30-day mortality at least as strong as age, left ventricular function, and renal function. In contrast, anti-Xa activity did not predict major bleeding complications within the range of anti-Xa levels observed in this study. CONCLUSIONS: In this large unselected cohort of patients with UA/NSTEMI patients, low anti-Xa activity on enoxaparin treatment is independently associated with 30-day mortality, which highlights the need for achieving at least the minimum prescribed anti-Xa level of 0.5 IU/mL with enoxaparin whenever possible.

Effects of Abciximab on the architecture of platelet-rich clots in patients with acute myocardial infarction undergoing primary coronary intervention.

BACKGROUND: Abciximab plus aspirin improves the TIMI 3 flow rate of the infarct-related artery in patients treated with either percutaneous coronary intervention or thrombolysis. The present study investigated whether the reperfusion efficacy of abciximab relates to modifications of clot architecture in patients admitted for acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 23 AMI patients in the Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long term follow-up (ADMIRAL) trial received, in a double-blind fashion, either abciximab (n=13) or placebo (n=10) before primary stenting. Viscoelastic (G' in dyne/cm(2)) and morphological (mean platelet aggregate surface area [SAG] in micrometer(2)) indexes of ex vivo platelet-rich clots (PRC) were assessed in a double-blind fashion before and after the bolus administration of abciximab or placebo. G' and SAG reflect the mechanical and morphological impact of activated platelets on the PRC fibrin network, respectively. Abciximab administration reduced G' by 63% (P=0.0001) and SAG by 65% (P=0.0007), and no effect was seen in the placebo group. These abciximab-related changes increased fibrin exposure as a consequence of the platelet-aggregate surface reduction and may have improved endogenous fibrinolysis. These effects were identified in all patients, independent of previous heparin administration. CONCLUSIONS: Abciximab dramatically reduces platelet aggregate size and increases the fibrin accessibility of ex vivo PRC in AMI patients. These modifications could participate in the better coronary artery patency observed with abciximab.