RESUMEN
BACKGROUND: Up to 25% of patients with ST elevation myocardial infarction (STEMI) have ST segment re-elevation after initial regression post-reperfusion and there are few data regarding its prognostic significance.MethodsâandâResults:A standard 12-lead electrocardiogram (ECG) was recorded in 662 patients with anterior STEMI referred for primary percutaneous coronary intervention (PPCI). ECGs were recorded 60-90 min after PPCI and at discharge. ST segment re-elevation was defined as a ≥0.1-mV increase in STMax between the post-PPCI and discharge ECGs. Infarct size (assessed as creatine kinase [CK] peak), echocardiography at baseline and follow-up, and all-cause death and heart failure events at 1 year were assessed. In all, 128 patients (19%) had ST segment re-elevation. There was no difference between patients with and without re-elevation in infarct size (CK peak [mean±SD] 4,231±2,656 vs. 3,993±2,819 IU/L; P=0.402), left ventricular (LV) ejection fraction (50.7±11.6% vs. 52.2±10.8%; P=0.186), LV adverse remodeling (20.1±38.9% vs. 18.3±30.9%; P=0.631), or all-cause mortality and heart failure events (22 [19.8%] vs. 106 [19.2%]; P=0.887) at 1 year. CONCLUSIONS: Among anterior STEMI patients treated by PPCI, ST segment re-elevation was present in 19% and was not associated with increased infarct size or major adverse events at 1 year.
Asunto(s)
Infarto de la Pared Anterior del Miocardio , Electrocardiografía , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Infarto de la Pared Anterior del Miocardio/sangre , Infarto de la Pared Anterior del Miocardio/fisiopatología , Infarto de la Pared Anterior del Miocardio/cirugía , Creatina Quinasa/sangre , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/cirugía , Remodelación VentricularRESUMEN
BACKGROUND: Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. METHODS: CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. RESULTS: Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. CONCLUSIONS: The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.
Asunto(s)
Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea , Biomarcadores/sangre , Angiografía Coronaria , Método Doble Ciego , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Masculino , Infarto del Miocardio/fisiopatología , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction. METHODS: We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction. RESULTS: The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected. CONCLUSIONS: In our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.
Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Ciclosporina/uso terapéutico , Proteínas de Transporte de Membrana Mitocondrial/antagonistas & inhibidores , Infarto del Miocardio/terapia , Daño por Reperfusión Miocárdica/prevención & control , Premedicación , Área Bajo la Curva , Biomarcadores/sangre , Terapia Combinada , Creatina Quinasa/sangre , Ciclosporina/efectos adversos , Ciclosporina/sangre , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Poro de Transición de la Permeabilidad Mitocondrial , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Proyectos Piloto , Método Simple Ciego , Troponina I/sangreRESUMEN
BACKGROUND AIMS: Starting from experimental data proposing hematopoietic stem cells as candidates for cardiac repair, we postulated that human peripheral blood (PB) CD34+ cells mobilized by hematopoietic growth-factor (G-CSF) would contain cell subpopulations capable of regenerating post-ischemic myocardial damages. METHODS: In a phase I clinical assay enrolling seven patients with acute myocardial infarct, we directly delivered to the injured myocardium autologous PB CD34+ cells previously mobilized by G-CSF, collected by leukapheresis and purified by immunoselection. In parallel, we looked for the eventual presence of cardiomyocytic and endothelial progenitor cells in leukapheresis products of these patients and controls, using flow cytometry, reverse transcription-quantitative (RTQ)-polymerase chain reaction (PCR), cell cultures and immunofluorescence analyzes. RESULTS: The whole clinical process was feasible and safe. All patients were alive at an average follow-up of 49 months (range 24-76 months). Improvement of heart function parameters became obvious from the third month following cell reinjection. Left ventricular ejection fraction values progressively and dramatically increased with time, associated with PetScan demonstration of myocardial structure regeneration and revascularization and New York Heart Association (NYHA) grade improvement. Furthermore, we identified PB CD34+ cell subpopulations expressing characteristics of both immature and mature endothelial and cardiomyocyte progenitor cells. In vitro CD34+ cell cultures on a specific medium induced development of adherent cells featuring morphologies, gene expression and immunocytochemistry characteristics of endothelial and cardiac muscle cells. CONCLUSIONS: Mobilized CD34+ cells contain stem cells committed along endothelial and cardiac differentiation pathways, which could play a key role in a proposed two-phase mechanism of myocardial regeneration after direct intracardiac delivery, probably being responsible for the long-term clinical benefit observed.
Asunto(s)
Antígenos CD34/metabolismo , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética , Infarto del Miocardio/fisiopatología , Miocardio/patología , Células Madre/citología , Adulto , Anciano , Adhesión Celular/efectos de los fármacos , Desdiferenciación Celular/efectos de los fármacos , Células Cultivadas , Vías de Administración de Medicamentos , Células Endoteliales/citología , Células Endoteliales/metabolismo , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/farmacología , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Células Madre/efectos de los fármacos , Células Madre/metabolismo , Volumen Sistólico/efectos de los fármacos , Volumen Sistólico/fisiología , Factores de Tiempo , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Postinfarction management of patients must be individualized. The essential prognostic factor is the ejection fraction, measured at one month. The four basic drugs to be used in combination are antithrombotics, beta-blockers, converting enzyme inhibitors and statins. The objective of treatment is to reach the dose regimens used in clinical trials. Cardiovascular rehabilitation and treatment education must be proposed widely to improve control of risk factors, explain the role of each drug prescribed and teach the appropriate use of nitroglycerin and of emergency medical services. Indications for myocardial revascularization depend on the coronary anatomy. Indications for an implantable defibrillator and for cardiac replacement depend on the ejection fraction and on the existence of heart failure uncontrolled by drug treatment.
Asunto(s)
Infarto del Miocardio/terapia , Fármacos Cardiovasculares/uso terapéutico , Trasplante de Células , Desfibriladores Implantables , Trasplante de Corazón , Humanos , Revascularización MiocárdicaRESUMEN
BACKGROUND: The rise in cardiac troponin I after ST-elevation myocardial infarction treated by primary percutaneous coronary interventions (PCIs) is predictive of infarct size and left ventricular ejection fraction (LVEF). However, the comparative value of C-reactive protein (CRP) and troponin I for infarct size evaluation and the respective relationships between these biomarkers and mortality have not been investigated. METHODS: We studied 87 patients who underwent primary PCI for ST-elevation myocardial infarction. Concentrations of troponin I and CRP were measured before and for 72 hours after PCI. Infarct size was measured by the cumulative release of alpha-hydroxybutyrate deshydrogenase during the 72 hours after PCI (QHBDH72) and by delayed radionuclide LVEF (at 4.6 +/- 1.7 weeks). RESULTS: Concentrations of CRP at peak and at 24, 48 and 72 hours, and of troponin I at 6 and 72 hours, correlated with QHBDH72 and LVEF. In single variable analysis, at a mean follow-up of 42 +/- 8 months, Killip score of 3 to 4, CRP at baseline and at 48 hours, and troponin I at 6 and 72 hours were related to mortality. By multiple variable analysis, Killip score (OR 9.9, CI 1.6-58.8) and troponin I at 72 hours (OR 9.43, CI 2.1-43.5) were the only independent predictors of mortality. CONCLUSIONS: Plasma concentrations of CRP and troponin I after PCI were related to infarct size and mortality. However, Killip class and troponin I at 72 hours were the only independent predictors of mortality at long-term follow-up.
Asunto(s)
Angioplastia Coronaria con Balón , Proteína C-Reactiva/metabolismo , Infarto del Miocardio/sangre , Infarto del Miocardio/terapia , Miocardio/metabolismo , Stents , Troponina I/sangre , Anciano , Angioplastia Coronaria con Balón/efectos adversos , Enfermedades Cardiovasculares/mortalidad , Electrocardiografía , Femenino , Humanos , Hidroxibutirato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Mortalidad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/fisiopatología , Concentración Osmolar , Valor Predictivo de las Pruebas , Pronóstico , Ventriculografía con Radionúclidos , Stents/efectos adversos , Volumen Sistólico , Factores de TiempoRESUMEN
BACKGROUND: Incomplete ST-segment resolution (STR) after successful primary angioplasty for acute myocardial infarction (AMI) is associated with a poor prognosis. We used intracoronary Doppler velocimetry to investigate whether incomplete STR after primary angioplasty is a marker of severe microcirculatory dysfunction. METHODS AND RESULTS: Fifty patients with < or =12-hour AMI underwent successful primary angioplasty and systematic stenting with a Doppler guidewire. Patients with incomplete (<50%) STR 60 minutes after TIMI 3 flow was restored had flow velocity features suggestive of severe microcirculatory dysfunction, including a higher incidence of early systolic retrograde flow (41% versus 9%, P=0.007) and lower coronary flow velocity reserve (CVR, 1.3 versus 1.6, P<0.001). CVR improved immediately after stenting in patients with > or =50% STR but not in patients with <50% STR. There was a significant correlation between STR and poststent CVR. At 3 months, CVR was similar in patients with <50% and > or =50% STR. However, left ventriculography indicated lower global (42% versus 55%, P=0.001) and regional (16% versus 20%, P=0.03) left ventricular ejection fractions and 201Tl rest-redistribution scintigraphy indicated a larger infarct size (34% versus 16% 201Tl defect, P=0.007) in patients with <50% STR. CONCLUSIONS: After successful primary angioplasty with systematic stenting, <50% STR is a marker of severe albeit transient microcirculatory dysfunction in patients with AMI and is associated with more extensive myocardial damage.
Asunto(s)
Electrocardiografía , Microcirculación/diagnóstico por imagen , Infarto del Miocardio/diagnóstico , Stents , Anciano , Angioplastia Coronaria con Balón , Biomarcadores , Velocidad del Flujo Sanguíneo , Implantación de Prótesis Vascular , Circulación Coronaria , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Vasos Coronarios/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Microcirculación/fisiopatología , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/cirugía , Valor Predictivo de las Pruebas , Volumen Sistólico , Ultrasonografía Doppler , Ultrasonografía Intervencional , Función Ventricular IzquierdaRESUMEN
OBJECTIVES: We investigated the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention (PCI). BACKGROUND: Thus far, there is no established systemic pharmacologic approach for the prevention of restenosis after PCIs. Five small studies reported encouraging results for calcium channel blockers. METHODS: Our randomized double-blind trial included 700 consecutive patients with successful PCI of a native coronary artery. Patients received the calcium channel blocker verapamil, 240 mg twice daily for six months, or placebo. Primary clinical end point was the composite rate of death, myocardial infarction, and target vessel revascularization (TVR) during one-year follow-up; the angiographic end point was late lumen loss at the six-month follow-up angiography. RESULTS: We obtained complete clinical follow-up in 95% of the patients, and scheduled angiography was performed in 94%. The proportion of patients treated with stents was 83%. The primary clinical end point was reached in 67 (19.3%) patients on verapamil and in 103 (29.3%) patients on placebo (relative risk [RR] 0.66 [95% confidence interval (CI) 0.48 to 0.89]; p = 0.002). This difference between the groups was driven by TVR (17.5% with verapamil vs. 26.2% with placebo; RR 0.67 [95% CI 0.49 to 0.93]; p = 0.006). Late lumen loss was 0.74 +/- 0.70 mm with verapamil and 0.81 +/- 0.75 mm with placebo (p = 0.11). Compared with placebo, verapamil reduced the rate of restenosis > or =75% (7.8% vs. 13.7%; RR 0.57 [95% CI 0.35 to 0.92]; p = 0.014). CONCLUSIONS: Verapamil compared with placebo improves long-term clinical outcome after PCI of native coronary arteries by reducing the need for TVR. This was caused by a reduction in the rate of high-grade restenosis.
Asunto(s)
Angioplastia Coronaria con Balón , Bloqueadores de los Canales de Calcio/uso terapéutico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/prevención & control , Verapamilo/uso terapéutico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The aim of this study was to investigate the ability of troponin I (cTnI) levels to predict myocardial infarction size in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). In 87 patients with STEMI undergoing primary PCI, serial plasma concentrations of cTnI and alpha-hydroxybutyrate deshydrogenase (HBDH) were measured before PCI and over the following 72 h. Enzymatic infarct size was estimated by the cumulative release of HBDH during the 72 h following PCI (QHBDH72). Delayed radionuclide left ventricular ejection fraction (LVEF) was measured in 63 patients. While cTnI concentrations at admission did not correlate with QHBDH72 or with LVEF, from the 3rd to the 72nd h following PCI, they did correlated with QHBDH72 (P<0.001; R: 0.76-0.86) and with LVEF (P<0.001; R: -0.42 to -0.50). Receiver-operator characteristic (ROC) curve analysis showed that admission concentrations of cTnI could not predict either a large infarct size (i.e., QHBDH72>10 g-eq l(-1)) or a low LVEF (i.e., LVEF<40%). However, 6 h and up until 72 h after PTCA, cTnI concentrations were predictive of large enzymatic infarct size (sensitivity: 91 and 95%, specificity: 90 and 87%, respectively) and of LVEF under 40% (sensitivity: 75 and 77%, specificity: 90 and 78%, respectively). Thus, our study suggests that in contrast with admission cTnI concentration, cTnI levels following primary PCI represent a reliable tool for predicting large enzymatic infarct size and may help in selecting patients with a high risk of low LVEF at 1 month.
Asunto(s)
Angioplastia Coronaria con Balón , Electrocardiografía , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Troponina I/metabolismo , Disfunción Ventricular Izquierda/metabolismo , Disfunción Ventricular Izquierda/terapia , Anciano , Angiografía Coronaria , Femenino , Humanos , Hidroxibutirato Deshidrogenasa/metabolismo , Masculino , Persona de Mediana Edad , Admisión del Paciente , Valor Predictivo de las Pruebas , Curva ROC , Estadística como Asunto , Volumen Sistólico/fisiología , Factores de TiempoRESUMEN
BACKGROUND: The value of prehospital initiation of glycoprotein IIb/IIIa inhibitors remains a controversial issue. We sought to investigate whether in-ambulance initiation of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) improves ST-segment elevation resolution (STR) after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: MISTRAL (Myocardial Infarction with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace) is a prospective, randomized, double-blind study. Two hundred and fifty-six patients with acute STEMI were allocated to receive abciximab either in the ambulance (ambulance group, n=127) or in the catheterization laboratory (hospital group, n=129). The primary end point was complete (>70%) STR after PCI. Complete STR was not significantly different between the 2 groups (before PCI, 21.6% versus 15.5%, P=0.28; after PCI, 70.3% versus 65.8%, P=0.49). Thrombolysis In Myocardial Infarction (TIMI) 2 to 3 flow rates before PCI tended to be higher in the ambulance group (46.8% versus 35%, P=0.08) but not after PCI (70.3% versus 65.8%, P=0.49). Slow flow tended to be lower (5.6% versus 13.4%, P=0.07), and distal embolization occurred significantly less often in the ambulance group (8.1% versus 21.1%, P=0.008). One- and 6-month major adverse cardiac event rates were low and similar in both groups. CONCLUSIONS: Early ambulance administration of abciximab in STEMI did not improve either STR or TIMI flow rate after PCI. However, it tended to improve TIMI flow pre-PCI and decreased distal embolization during procedure. Larger studies are needed to confirm these results.
Asunto(s)
Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/administración & dosificación , Anticoagulantes/administración & dosificación , Servicios Médicos de Urgencia , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Abciximab , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticoagulantes/efectos adversos , Método Doble Ciego , Electrocardiografía , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/cirugía , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Early reperfusion during evolving myocardial infarction is essential for saving myocardium and patients' lives. Nevertheless, lethal reperfusion injury can occur, limiting myocardial salvage. Numerous experimental studies have proved the deleterious effects of reoxygenating endothelial cells and cardiomyocytes. The major breakthrough was the proof that the success of myocardial reperfusion can be modified by preconditioning and, more recently, by postconditioning, a form of progressive and interrupted reperfusion. Three theories have been put forward to explain reperfusion injury: (1) oxidative stress resulting in a burst of oxygen-radical formation, which can cause membrane damage; (2) the energy paradox, which suggests that restarting energetic mitochondrial machinery results in myofibrillar hypercontracture, cytoskeleton fragility and membrane rupture; and (3) the role of inflammation, which addresses the effects of leucocyte accumulation and activation. Fortunately, reperfusion injury salvage kinases can be up-regulated and in some circumstances may block, in a manner similar to pre- or postconditioning, the diabolical cycle leading to necrosis and/or apoptosis of viable cells. The end effectors of the survival system are two mitochondrial channels - the mK-ATP channel and the mitochondrial permeability transition pore. Better understanding of these salutary molecular mechanisms and their triggers may result in a new era of reperfusion techniques.
Asunto(s)
Infarto del Miocardio/complicaciones , Daño por Reperfusión Miocárdica/etiología , Humanos , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Daño por Reperfusión Miocárdica/metabolismo , Estrés OxidativoRESUMEN
Two forms of reperfusion injury can occur in patients with ST-segment elevation acute myocardial infarction who are undergoing primary angioplasty: no-reflow phenomenon and reperfusion syndrome. No-reflow, defined as low or no distal perfusion despite removal of epicardial occlusion, can be detected by angiographic flow, myocardial blush grade and contrast echocardiography. Reperfusion syndrome involves haemodynamic and rhythmic disturbances, but an overall paradoxical ST-segment increase. A variety of mechanisms give rise to no-reflow, including distal embolization, leucocyte plugging and vasoconstriction. Reperfusion syndrome reflects, at least in part, the cardiomyocyte component of reperfusion injury. Reperfusion injury can be predicted from the initial electrocardiogram, especially when QRS complex distortion is observed. Pharmacological prevention of reperfusion injury has been tested in a number of trials; the most useful drugs available currently are glycoprotein IIb/IIIa receptor blockers and adenosine. Thrombus aspiration leads to faster and greater ST-segment resolution. Postconditioning (also called staccato reperfusion) is a new strategy that has produced highly encouraging results, although it has been tested only in a small randomized study. New tools are required to enable thrombus aspiration and postconditioning to be carried out simultaneously. Pharmacological postconditioning can be anticipated in the near future, as many drugs appear to achieve the same positive effect as mechanical modified reperfusion.
Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Circulación Coronaria , Infarto del Miocardio/terapia , Daño por Reperfusión Miocárdica/etiología , Reperfusión Miocárdica/efectos adversos , Miocardio/patología , Fenómeno de no Reflujo/etiología , Adenosina/uso terapéutico , Animales , Electrocardiografía , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Daño por Reperfusión Miocárdica/prevención & control , Nicorandil/uso terapéutico , Fenómeno de no Reflujo/patología , Fenómeno de no Reflujo/fisiopatología , Fenómeno de no Reflujo/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Trombectomía/instrumentación , Resultado del Tratamiento , Vasodilatadores/uso terapéuticoRESUMEN
OBJECTIVES: We investigated whether maintenance therapy with clopidogrel 150 mg/day produces greater platelet inhibition than the standard 75-mg/day dose and whether the higher maintenance dose increases platelet inhibition in low responders to clopidogrel 75 mg/day. BACKGROUND: Patients show interindividual variability in their platelet response to clopidogrel. Low responders could potentially obtain greater clinical benefit from greater doses of clopidogrel. METHODS: One hundred fifty-three elective percutaneous coronary intervention patients were randomized to clopidogrel 150 mg/day (n = 58) or 75 mg/day (n = 95) for 4 weeks, with vasodilator-stimulated phosphoprotein assay-guided switching to clopidogrel 150 mg/day after 2 weeks in low responders (platelet reactivity index >or=69%). All patients received aspirin 75 mg/day. RESULTS: After 2 weeks, clopidogrel 150 mg/day produced a significantly lower platelet reactivity index than clopidogrel 75 mg/day (43.9 +/- 17.3% vs. 58.6 +/- 17.7%; p < 0.0001). The proportion of low responders was significantly lower in patients randomized to clopidogrel 150 mg/day than in those randomized to clopidogrel 75 mg/day (8.6% vs. 33.7%; p = 0.0004). In the clopidogrel 75 mg/day group, 64.5% (20 of 31) of low responders became responders after switching to clopidogrel 150 mg/day for 2 weeks. No major bleeds occurred during the study; the incidence of minor bleeds was similar in each treatment group. CONCLUSIONS: In elective percutaneous coronary intervention patients, a 150-mg/day clopidogrel maintenance dose produces greater inhibition of platelet function than clopidogrel 75 mg/day. In low responders to clopidogrel 75 mg/day, switching to clopidogrel 150 mg/day overcomes low responsiveness in a majority of patients. These findings warrant further clinical evaluation. (VASP-02; EudraCT number: 2004-005230-40).