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G Montalescot

Publications and source records attributed to G Montalescot.

At least 37 records · Page 2Linked to original sources
PubMed2003

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.

Angioplasty, Balloon, Coronary↗
PubMed2003

Acute release of plasminogen activator inhibitor-1 in ST-segment elevation myocardial infarction predicts mortality.

BACKGROUND: A few studies have suggested that von Willebrand factor (vWF) or plasminogen activator inhibitor-1 (PAI-1) can be associated with outcomes of acute coronary syndromes. The present study was designed to assess the acute release of these markers in ST-segment elevation myocardial infarction (STEMI) and their relations to death. METHODS AND RESULTS: In 153 consecutive patients with STEMI, vWF and PAI-1 antigens were measured on admission (H0) and 24 hours later (H24). At 30 days, the death rate was 7.2%. Heart failure (Killip stage > or =3) on admission was present in 13.7% of patients. The acute release of PAI-1 (H24-H0, in ng/mL) and of vWF (H24-H0, in %) was dramatically higher in patients who died than in those who survived (46.9+/-26.3 versus -0.6+/-2.8 ng/mL, P=0.0001 and 65.8+/-20.0% versus 10.0+/-5.1%, P=0.004 for PAI-1 and vWF, respectively) and in patients developing heart failure compared with those without (24.8+/-10.1 versus -1.1+/-3.3 ng/mL, P=0.004 and 47.3+/-11.0% versus 8.1+/-5.6%, P=0.005 for PAI-1 and vWF, respectively). The release of PAI-1 correlated weakly with the left ventricular ejection fraction (R=-0.195, P=0.01) and the peak of troponin (R=0.149, P=0.045). Postangioplasty TIMI-3 flow and the acute release of PAI-1 were the only 2 independent predictors of death at 30 days. CONCLUSIONS: The acute release of vWF and PAI-1 over the first 24 hours of STEMI is associated with death and heart failure. The acute rise of PAI-1 is also a strong independent predictor of death at 30 days.

Aged↗
PubMed2003

[FACT: French national registry of acute coronary syndromes. Specific study of French general hospital centers].

UNLABELLED: The FACT registry is currently the French registry including the greatest number of patients with acute coronary syndromes. PURPOSE: The study presents epidemiologic data, modalities and delays for medical admission. METHOD: Three thousand nine hundred and two patients were included in FACT by 362 French centers of cardiology between 06/01/2003 and 03/02/2003. One thousand eight hundred and ten patients, who had been placed in the cardiology departments of French general hospitals, were isolated from this registry. The French general hospitals represented 50.8% of the 362 centers. In order to clarify the study, these patients were divided into three groups: group A: patients without ST segment elevation but with suggestive ECG modifications; group B: patients with ST segment elevation; group C: all other patients. The results were mainly studied for groups A and B and compared. These results were also compared to those of the FACT registry and of other registries. RESULTS: The results show that the average delay for admission is 2.9 h after a first delay between the pain and the help of 6.7 h. The first intervening party is a general practitioner (36.4%) then the SAMU (31.6%) and finally the emergency departments (18.7%). 16.6% of the patients from group B undergo pre-hospital thrombolysis. The recommendations of the European Society of Cardiology are widely applied except for the most recent of them since only 27.6% of the patients from group A having a TIMI score > or = 5 receive an anti-GIIB IIIA treatment. The reasons of the non-prescription of the recommended classes are mostly linked to contra-indication and intolerance. The strategy of coronary reopening mainly depends on the presence or the absence in the department of an available medical equipment for angioplasty. If there is one, the percentage of primary angioplasty reaches 54.2% and the percentage of thrombolysis 7.9%. On the opposite, there is 8.3% of angioplasty and 54.2% of thrombolysis for the unequipped centers. The global mortality reaches 5.8% but is inversely proportional to the level of equipment of the departments: 5.9% for the departments with angioplasty, 11% for the departments with coronarography but without angioplasty and 13.8% for the departments without any interventional equipment. Nevertheless, the age of the patients is different and this influences the results: we notice that the less equipped the department is, the older the patients are. CONCLUSION: The FACT registry and the data from the general hospitals give the opportunity to think about the possibilities to improve the delays of call to the first intervening party (more particularly to the SAMU) but it also allows us to think about how to better organize the geographical distribution giving access to a medical equipment for angioplasty. All these information will also help the cardiologists to gather around the recommendations by convincing them that the benefit/risk ratio is positive.

Adult↗
PubMed2003

Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE).

AIMS: There have been no large observational studies attempting to identify predictors of major bleeding in patients with acute coronary syndromes (ACS), particularly from a multinational perspective. The objective of our study was thus to develop a prediction rule for the identification of patients with ACS at higher risk of major bleeding. METHODS AND RESULTS: Data from 24045 patients from the Global Registry of Acute Coronary Events (GRACE) were analysed. Factors associated with major bleeding were identified using logistic regression analysis. Predictive models were developed for the overall patient population and for subgroups of patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina. The overall incidence of major bleeding was 3.9% (4.8% in patients with STEMI, 4.7% in patients with NSTEMI and 2.3% in patients with unstable angina). Advanced age, female sex, history of bleeding, and renal insufficiency were independently associated with a higher risk of bleeding (P<0.01). The association remained after adjustment for hospital therapies and performance of invasive procedures. After adjustment for a variety of potential confounders, major bleeding was significantly associated with an increased risk of hospital death (adjusted odds ratio 1.64, 95% confidence interval 1.18, 2.28). CONCLUSIONS: In routine clinical practice, major bleeding is a relatively frequent non-cardiac complication of contemporary therapy for ACS and it is associated with a poor hospital prognosis. Simple baseline demographic and clinical characteristics identify patients at increased risk of major bleeding.

Adult↗
PubMed2003

[Role of glycoprotein IIb/IIIa inhibitors in the management of acute coronary syndromes].

Antiplatelet therapy is a cornerstone in the medical management of acute coronary syndromes. Three classes of antiplatelet drugs are available in this setting: acetylsalicylic acid, thienopyridines, and glycoprotein IIb/IIIa antagonists. During the last ten years, numerous clinical trials have been conducted in large populations of patients suffering from acute coronary syndromes. Further investigations are in progress. In the light of these results, the respective roles of the different antiplatelet drugs have been more precisely defined, in terms of class preference as well as in terms of the combination of several antiplatelet drugs and of antiplatelet drugs with other therapies, including non fractionated--or low molecular weight--heparin and non-invasive or invasive revascularisation procedures. In the present article, we review the results of the major published or non published trials that addressed the role of glycoprotein IIb/IIIa antagonists in the management of acute coronary syndromes. Based on these results, the current therapeutic guidelines for clinical practice issued by the American and European cardiology societies are given in the conclusion, with their level of evidence.

Acute Disease↗
PubMed2002

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.

Abciximab↗
PubMed2002

Transfer for primary angioplasty: who and how?

Randomised trials have led to the conclusion that percutaneous coronary intervention (PCI) is the best reperfusion strategy for most patients with acute myocardial infarction (AMI). However, these trials have limited application to routine practice. Modern trials of mechanical reperfusion strategies need to take account of logistics, transfer times, and adjunctive drug treatment during transfer (facilitated PCI). Such PCI protocols need to be judged against very early thrombolysis with modern agents. This has been the thrust behind a series of recent studies addressing these "real world" issues in early AMI management

Angioplasty, Balloon, Coronary↗
PubMed2002

[Non-ST acute coronary syndromes].

Acute coronary syndromes are the first cause of death in France. Unstable angina is the most frequent acute coronary syndrome. Risk stratification to predict morbimortality and the risk of major hemorrhage is the key step of the medical approach. Combined antithrombotic therapy (aspirine + clopidogrel + LMWH) has led to a substantial reduction of major coronary events with a good tolerance because of the short duration of such aggressive strategy. This combined antithrombotic also allowed to increase the benefit of an early invasive strategy including coronary angiogram with stent percutaneous coronary intervention.

Angina, Unstable↗
PubMed2001

Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.

BACKGROUND: When administered in conjunction with primary coronary stenting for the treatment of acute myocardial infarction, a platelet glycoprotein IIb/IIIa inhibitor may provide additional clinical benefit, but data on this combination therapy are limited. METHODS: We randomly assigned 300 patients with acute myocardial infarction in a double-blind fashion either to abciximab plus stenting (149 patients) or placebo plus stenting (151 patients) before they underwent coronary angiography. Clinical outcomes were evaluated 30 days and 6 months after the procedure. The angiographic patency of the infarct-related vessel and the left ventricular ejection fraction were evaluated at 24 hours and 6 months. RESULTS: At 30 days, the primary end point--a composite of death, reinfarction, or urgent revascularization of the target vessel--had occurred in 6.0 percent of the patients in the abciximab group, as compared with 14.6 percent of those in the placebo group (P=0.01); at 6 months, the corresponding figures were 7.4 percent and 15.9 percent (P=0.02). The better clinical outcomes in the abciximab group were related to the greater frequency of grade 3 coronary flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) in this group than in the placebo group before the procedure (16.8 percent vs. 5.4 percent, P=0.01), immediately afterward (95.1 percent vs. 86.7 percent, P=0.04), and six months afterward (94.3 percent vs. 82.8 percent, P=0.04). One major bleeding event occurred in the abciximab group (0.7 percent); none occurred in the placebo group. CONCLUSIONS: As compared with placebo, early administration of abciximab in patients with acute myocardial infarction improves coronary patency before stenting, the success rate of the stenting procedure, the rate of coronary patency at six months, left ventricular function, and clinical outcomes.

Abciximab↗
PubMed2001

Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention.

OBJECTIVES: The goal of this study was to test: 1) if platelet glycoprotein IIb/IIIa (GP IIb/IIIa) blockade with abciximab bolus plus 12-h infusion reduces mortality after percutaneous coronary intervention (PCI); 2) if prevention of early myocardial infarction (MI) after PCI is a mechanism for reducing mortality; and 3) for risk factors for mortality after PCI. BACKGROUND: Studies of PCI suggest that MI after intervention is predictive of mortality. Abciximab, a platelet GP IIb/IIIa receptor inhibitor, has consistently reduced the incidence of MI among PCI patients in several trials. The presumed mechanism is prevention of platelet thrombus associated with vessel wall injury and downstream embolization into the microcirculation. METHODS: In eight trials, 5,154 patients were randomized to a regimen comprising conventional therapy plus a bolus of abciximab within 1 h before PCI followed by a 12-h infusion; 4,136 controls were randomized to conventional therapy alone. Patient follow-up from six months to three years was available. Survival differences are examined using proportional hazards regression and survival curves. RESULTS: A hazard ratio of 0.71 (95% confidence interval 0.57 to 0.89; p = 0.003) suggests a mortality benefit with abciximab. The absolute reduction in mortality was estimated to be 0.5% through 30 days, 0.7% through six months, 0.9% through one year and 1.8% through three years. Early MI explained 18% of the observed mortality benefit at one year. Multivariate regression suggests that patients with advanced cardiovascular disease may derive the greatest mortality benefit from abciximab. CONCLUSIONS: The evidence from 9,290 randomized PCI patients shows a mortality benefit provided by abciximab bolus plus 12-h infusion.

Abciximab↗
PubMed2001

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.

Abciximab↗
PubMed2001

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.

Aged↗
PubMed2001

Enoxaparin in unstable angina patients with renal failure.

The dosage of the subcutaneous low molecular weight heparin enoxaparin in unstable angina patients undergoing coronary angiogram and coronary angioplasty depends clearly on the renal function. It should be significantly reduced to 64% of the standard dose (1 mg/kg per 12 h) in patients with severe renal failure (creatinine clearance<30 ml/min) to provide a safe anticoagulant profile.

Aged↗
PubMed2001

Disaggregation of in vitro preformed platelet-rich clots by abciximab increases fibrin exposure and promotes fibrinolysis.

The glycoprotein IIb/IIIa receptor inhibitor abciximab has been shown to facilitate the rate and the extent of pharmacological thrombolysis with recombinant tissue plasminogen activator (rtPA) in patients with acute myocardial infarction. However, the underlying mechanisms remain not fully determined. We sought to demonstrate that this facilitating effect of abciximab could be related to its potential to modify the clot architecture and the clot physical properties. Compared with fibrin-rich clots, platelets dramatically modified the in vitro properties of the fibrin network, leading to a significant increase of the permeability (K(s)) and the viscoelasticity (G') indexes but also leading to the appearance of platelet aggregates (surface area [S.ag]). These modifications resulted in a 2.6-fold decrease of the fibrinolysis rate when rtPA (1 nmol/L) was added before the initiation of clotting. Adding aspirin (100 microgram/mL) or abciximab (0.068 micromol/L) before the clotting of platelet-rich clots (PRCs) lowered K(s) by 50% and 70%, respectively (P<0.01), G' by 41% and 66%, respectively (P<0.01), and S.ag by 32% and 61%, respectively (P<0.01). As a consequence, the lysis speed was increased by 21% with aspirin (P<0.01) and 45% with abciximab (P<0.01). However, unlike aspirin, permeation of preformed PRCs with abciximab (0.068 micromol/L) decreased G' (37%, P<0.01), K(s) (35%, P<0.001) and S.ag (25%, P=NS) and resulted in a 27% (P<0.01) increase of the lysis speed when abciximab and rtPA (0.2 micromol/L) were simultaneously permeated. This effect was found to be time dependent and was observed only with early permeation, starting within the first 10 minutes of clotting. These changes in the physical properties of the PRC architecture suggest that fibrin is removed from the platelet-fibrin aggregates and reexposed into the surrounding fibrin network, increasing rtPA access to fibrin and therefore the fibrinolysis rate. The superiority of abciximab over aspirin in accelerating fibrinolysis of forming and preformed PRCs is related to its ability to modulate the interactions of fibrinogen and fibrin with platelets. These findings provide new mechanistic information on reperfusion therapy.

Abciximab↗
PubMed2001

[Whole blood viscosity measurement in acute myocardial infarction: feasibility and significance].

Thrombolytic agents and new antiplatelet drugs used in acute myocardial infarction (AMI) could change whole blood viscosity. The aim of this pilot trial is to compare blood viscosity at four shear rate levels among three groups of patients: AMI receiving thrombolysis with alteplase (n: 10), AMI eligible for primary angioplasty with abciximab (n: 10), healthy volunteers (n: 10). Viscosity measurement was obtained in 30 minutes with a Couette hemoviscosimeter. At baseline, blood viscosity level was higher in patients with acute coronary syndromes than in healthy volunteers (72 +/- 32 mPa.s versus 51 +/- 13 mPa.s, p<0.05). After thrombolysis, viscosity was higher at 90 minutes than at third day, paradoxically with fibrinogen elevation (72 +/- 32 mPa.s versus 58 +/- 27 mPa.s, p=0.01). In primary angioplasty with abciximab, viscosity decreased significantly (56 +/- 28 mPa.s versus 43 +/- 13 mPa.s, p=0.01). The effects of ionic contrast agent and abciximab are discussed. In healthy volunteers group, 100 mg aspirin once a day during 7 days reduces blood viscosity at high shear stress. The small size of the study population restricts correlation analysis with major clinical adverse events. A larger trial is necessary to evaluate the predictive value of whole blood viscosity in reocclusive and/or hemorrhagic events in those reperfusion strategies but also in case of thrombolytic agent and abciximab combination.

Adult↗
PubMed2001

[Review and future perspectives on low-molecular-weight heparin].

Low molecular weight heparins appear to be a better choice in patients with unstable angina than unfractionated heparin. Their favourable pharmacokinetic profile allows an excellent predictable dose-response with a subsequent rapidly effective and stable anticoagulation, which is ideal in the setting of percutaneous coronary intervention. Although direct comparisons between LMWH and UH are limited, substantial evidence exists that patients receiving LMWH can be safely brought to cardiac catheterization. Therefore, previous concern regarding transitioning such therapy from the medical service to the cardiac catheterization laboratory should not impede the upstream use of these agents. Direct i.v. injection of LMWH in the setting of elective PCI have also been shown to be safe and effective. Although UH remains an option in conjunction with GP IIb/IIIa inhibitors, there is substantial evidence that LMWH and GP IIb/IIIa inhibitor therapy can be used safely in combination. Patients with either chronic renal failure, mechanical valves or atrial fibrillation are other important issues which deserve additional prospective evaluation of the safety and the efficacy of LMWH. Development of a biological assay for monitoring either LMWH or GP IIb/IIIa receptor antagonists is another important issue in the setting of antithrombotic combinations which are now commonplace.

Angina, Unstable↗