RESUMEN
BACKGROUND: Previous investigators have shown that systemic markers of inflammation may be increased in patients with acute ischemic syndromes or after percutaneous coronary revascularization and that persistent elevation in these markers is predictive of excess risk of subsequent adverse cardiac events. By virtue of its cross-reactivity with the glycoprotein IIb/IIIa, avbeta3, and alphaMbeta2 receptors, abciximab may reduce inflammatory processes. Methods and Results-- Assays for the inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were performed on serum samples obtained from 160 patients in a placebo-controlled, randomized trial of abciximab during angioplasty. Eighty patients each had received a placebo or abciximab bolus plus a 12-hour infusion. Serum samples were drawn at baseline (before revascularization), 24 to 48 hours after study drug administration, and 4 weeks after study drug administration. Between baseline and 24 to 48 hours, the increase in C-reactive protein was 32% less in patients receiving abciximab than placebo (P=0.025); the rise in interleukin-6 levels was 76% less in the abciximab group (P<0.001); and the rise in tumor necrosis factor-alpha levels was 100% less with abciximab therapy (P=0.112). By 4 weeks, most marker levels had returned to baseline, with no significant differences between placebo and abciximab groups. CONCLUSIONS: Systemic markers of inflammation increase in the first 24 to 48 hours after angioplasty, but the magnitude of that rise is diminished by periprocedural abciximab. Some of the long-term clinical benefit derived from this agent may be related to an anti-inflammatory effect.
Asunto(s)
Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/administración & dosificación , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Inflamación/prevención & control , Inhibidores de Agregación Plaquetaria/administración & dosificación , Abciximab , Angioplastia Coronaria con Balón/efectos adversos , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Inflamación/sangre , Inflamación/etiología , Infusiones Intravenosas , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismo , Estados UnidosRESUMEN
BACKGROUND: Animal models of therapeutic angiogenesis have stimulated development of clinical application in patients with limited options for coronary revascularization. The impact of recombinant human vascular endothelial growth factor (rhVEGF) on myocardial perfusion in humans has not been reported. METHODS AND RESULTS: Fourteen patients underwent exercise (n=11), dobutamine (n=2), or dipyridamole (n=1) myocardial perfusion single photon emission CT (SPECT) before as well as 30 and 60 days after rhVEGF administration. After uniform processing and display, 2 observers blinded to the timing of the study and dose of rhVEGF reviewed the SPECT images. By a visual, semiquantitative 20-segment scoring method, summed stress scores (SSS) and summed rest scores (SRS) were generated. Although the SSS did not change from baseline to 30 days (21.6 versus 21.5; P=NS), the SRS improved after rhVEGF (13.2 versus 10.4; P<0.05). Stress and rest perfusion improved in >2 segments infrequently in patients treated with low-dose rhVEGF. However, 5 of 6 patients had improvement in >2 segments at rest and stress with the higher rhVEGF doses. Furthermore, although neither the SSS nor the SRS changed in patients treated with the low doses, the SRS decreased in the high-dose rhVEGF patients at 60 days (14.7 versus 10.7; P<0.05). Quantitative analysis was consistent with the visual findings but failed to demonstrate statistical significance. CONCLUSIONS: Although not designed to demonstrate rhVEGF efficacy, these phase 1 data support the concept that rhVEGF improves myocardial perfusion at rest and provide evidence of a dose-dependent effect.
Asunto(s)
Circulación Coronaria/efectos de los fármacos , Factores de Crecimiento Endotelial/administración & dosificación , Linfocinas/administración & dosificación , Cardiotónicos , Enfermedad Coronaria/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Dipiridamol , Dobutamina , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Factores de Crecimiento Endotelial/uso terapéutico , Prueba de Esfuerzo , Humanos , Inyecciones Intraarteriales , Linfocinas/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Tomografía Computarizada de Emisión de Fotón Único , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , VasodilatadoresRESUMEN
BACKGROUND: Antiplatelet therapy is the mainstay of the treatment and secondary prevention of cardiovascular and cerebrovascular ischemic events. We assessed the safety, tolerability, and pharmacodynamics of lotrafiban, an oral platelet glycoprotein IIb/IIIa inhibitor, as a secondary prevention strategy in patients with cerebrovascular or cardiovascular disease. METHODS AND RESULTS: Overall, 451 patients with a recent cardiovascular or cerebrovascular acute ischemic event were randomized in a double-blind fashion to 1 of 5 dosing regimens for 12 weeks: placebo or 5, 20, 50, or 100 mg lotrafiban, both twice daily with 300 to 325 mg/d aspirin. The primary end point was the incidence and tolerability of major and minor bleeding during treatment. Secondary end points included inhibition of platelet aggregation and clinical events. The placebo and lotrafiban 5-mg groups had similarly low rates of minor and major bleeding, but the 100-mg arm was terminated early because of excess major bleeding. Protocol-defined thrombocytopenia (<100 000 platelets/microL) occurred in 5 lotrafiban-treated patients (1.4%, 95% CI 0.2% to 2.7%) and 1 placebo patient (1.1%, 95% CI 0% to 3.1%). Three lotrafiban-treated patients had a nadir platelet count <20 000/microL (0.9%, 95% CI 0% to 1.8%). Lotrafiban produced dose-dependent inhibition of platelet aggregation; 5 mg lotrafiban did not differ significantly from placebo, whereas 100 mg inhibited aggregation by nearly 100%. CONCLUSIONS: -Lotrafiban provides dose-dependent platelet inhibition when administered to a range of patients with atherosclerosis. The level of platelet inhibition appears to correlate with bleeding risk and drug tolerability.
Asunto(s)
Benzodiazepinas , Enfermedad Coronaria/tratamiento farmacológico , Arteriosclerosis Intracraneal/tratamiento farmacológico , Piperidinas , Inhibidores de Agregación Plaquetaria/administración & dosificación , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Administración Oral , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombocitopenia/inducido químicamente , Resultado del TratamientoRESUMEN
BACKGROUND: Blockade of the platelet glycoprotein IIb/IIIa receptor with the monoclonal antibody fragment abciximab was shown in a placebo-controlled randomized trial to reduce the incidence of acute ischemic complications within 30 days among a broad spectrum of patients undergoing percutaneous coronary revascularization. The durability of clinical benefit in this setting has not been established. METHODS AND RESULTS: A total of 2792 patients enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG) trial were followed with maintenance of double-blinding for 1 year. Patients had been assigned at the time of their index coronary interventional procedure to receive placebo with standard-dose, weight-adjusted heparin (100 U/kg initial bolus), abciximab with standard-dose, weight-adjusted heparin, or abciximab with low-dose, weight-adjusted heparin (70 U/kg initial bolus). The primary outcome was the composite of death, myocardial infarction, or urgent repeat revascularization by 30 days; this composite end point and its individual components were also assessed at 6 months and 1 year. Rates of any repeat revascularization (urgent or elective), target vessel revascularization, and a composite of death, myocardial infarction, or any repeat revascularization were also reported. Follow-up at 1 year was 99% complete for survival status and 97% complete for other end points. By 1 year, the incidence of the primary composite end point was 16.1% in the placebo group, 9.6% in the abciximab with low-dose heparin group (P<0.001), and 9.5% in the abciximab with standard-dose heparin group (P<0.001). Each of the components of this composite end point was reduced to a similar extent. Nonurgent or target vessel repeat revascularization rates were not significantly decreased by abciximab therapy. Mortality rates over 1 year increased with increasing levels of periprocedural creatine kinase MB fraction elevation. CONCLUSIONS: Acute reductions in ischemic events after percutaneous coronary intervention by abciximab are sustained over follow-up to at least 1 year. Early periprocedural myocardial infarctions suppressed by this therapy are associated with long-term mortality rates.
Asunto(s)
Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/uso terapéutico , Enfermedad Coronaria/terapia , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Isquemia Miocárdica/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Abciximab , Anciano , Angioplastia Coronaria con Balón/estadística & datos numéricos , Biomarcadores , Causas de Muerte , Terapia Combinada , Puente de Arteria Coronaria/estadística & datos numéricos , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/enzimología , Creatina Quinasa/sangre , Método Doble Ciego , Quimioterapia Combinada , Urgencias Médicas , Femenino , Estudios de Seguimiento , Heparina/administración & dosificación , Heparina/uso terapéutico , Humanos , Incidencia , Isoenzimas , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Infarto del Miocardio/prevención & control , Isquemia Miocárdica/mortalidad , Estudios Prospectivos , Recurrencia , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Platelet glycoprotein IIb/IIIa blockade with abciximab (ReoPro) improves the clinical outcomes of percutaneous coronary intervention. This registry was conducted to characterize the effects of repeated administration of abciximab during intervention. METHODS AND RESULTS: We recruited 500 consecutive patients at 22 centers in the United States who were receiving abciximab for at least a second time during percutaneous coronary intervention. Safety was measured as the incidence of hypersensitivity reactions, major bleeding, and thrombocytopenia. Efficacy was assessed as event-free clinical success. Human antichimeric antibody (HACA) responses were also characterized. There were no cases of hypersensitivity (95% upper confidence bound, 0.3%), major bleeding, or death. Clinical success was 94.4%. Thrombocytopenia occurred in 23 patients (4.6%; 95% CI, 2.8% to 6.4%), including 12 (2.4%; 95% CI, 1.1% to 3.7%) who developed profound thrombocytopenia (<20x10(9) cells/L). In 2 patients (0.4%), profound thrombocytopenia did not develop until after hospital discharge; in 4 (0.8%), profound thrombocytopenia recurred despite platelet transfusion. Before a first readministration, a positive HACA titer was present in 22 of 454 patients (4.8%); after a first readministration, an additional 82 of 432 (19.0%) became HACA-positive. HACA did not neutralize the in vitro inhibition of platelet aggregation by abciximab or correlate with clinical events. CONCLUSIONS: The results, including overall rates of thrombocytopenia, were consistent with randomized clinical trials of first abciximab treatment. However, there was a shift from mild to profound thrombocytopenia, and cases of delayed presentation and of recurrent thrombocytopenia were seen. These findings suggest that indications and guidelines for first-time use apply to retreatment, particularly the systematic monitoring for thrombocytopenia.
Asunto(s)
Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/administración & dosificación , Enfermedad Coronaria/terapia , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Sistema de Registros/estadística & datos numéricos , Trombocitopenia/diagnóstico , Grado de Desobstrucción Vascular/efectos de los fármacos , Abciximab , Angioplastia Coronaria con Balón/efectos adversos , Anticuerpos/sangre , Anticuerpos/farmacología , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Aspirina/administración & dosificación , Enfermedad Coronaria/sangre , Supervivencia sin Enfermedad , Esquema de Medicación , Hemorragia/etiología , Heparina/administración & dosificación , Humanos , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Fragmentos Fab de Inmunoglobulinas/inmunología , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/inmunología , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Complicaciones Posoperatorias/prevención & control , Trombocitopenia/etiología , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. METHODS AND RESULTS: A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). CONCLUSIONS: In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.
Asunto(s)
Angioplastia Coronaria con Balón , Medios de Contraste/efectos adversos , Enfermedad Coronaria/terapia , Ácido Yoxáglico/efectos adversos , Ácidos Triyodobenzoicos/efectos adversos , Anciano , Angioplastia Coronaria con Balón/métodos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. METHODS AND RESULTS: Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACES: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve >/=95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P=0.006). Patients whose platelet function was <70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those >/=70% inhibited (P=0.009). By multivariate analysis, platelet function inhibition >/=95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P=0.04). CONCLUSIONS: Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.
Asunto(s)
Angioplastia Coronaria con Balón , Cardiopatías/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tirosina/análogos & derivados , Abciximab , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Plaquetas/efectos de los fármacos , Plaquetas/fisiología , Estudios de Cohortes , Eptifibatida , Femenino , Cardiopatías/inducido químicamente , Humanos , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Modelos Logísticos , Masculino , Análisis Multivariante , Péptidos/efectos adversos , Péptidos/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/efectos adversos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Tirofibán , Tirosina/efectos adversos , Tirosina/uso terapéuticoRESUMEN
The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trial was a randomized, multicenter study performed to determine whether immediate or elective (7 day) coronary angioplasty was preferable once infarct vessel recanalization had been confirmed. In addition, a major focus of the effort was to collect detailed information about the clinical course and outcome of all 386 patients entered into the trial, whether randomized or not. This article reports the major end points of acute and follow-up mortality, the incidence and timing of recurrent ischemic events and acute and convalescent infarct-vessel patency. The optimal timing of coronary angioplasty and intravenous tissue plasminogen activator (rt-PA) administration is discussed. The subsets of patients who: 1) were unsuccessfully treated with rt-PA; 2) had a minimal residual (less than 50%) lesion after rt-PA; or 3) underwent emergency coronary bypass surgery are presented. A current practical approach to acute intervention is extrapolated from the TAMI results.
Asunto(s)
Angioplastia de Balón , Vasos Coronarios , Fibrinolíticos/uso terapéutico , Infarto del Miocardio/terapia , Cateterismo Cardíaco , Ensayos Clínicos como Asunto , Terapia Combinada , Angiografía Coronaria , Urgencias Médicas , Ventrículos Cardíacos/fisiopatología , Humanos , Infarto del Miocardio/mortalidad , Distribución Aleatoria , Proteínas Recombinantes/uso terapéutico , Recurrencia , Factores de Tiempo , Activador de Tejido Plasminógeno/uso terapéutico , Grado de Desobstrucción Vascular/efectos de los fármacosRESUMEN
In the first three phases of Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trials, 708 patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and underwent detailed assessment of clinical, angiographic and ventriculographic outcomes. The cumulative experience and data base afford the opportunity to address several important questions regarding aggressive therapy of myocardial infarction. These include predictive factors of in-hospital mortality, improvement of left ventricular function and the occurrence of recurrent ischemia. Consideration of practical issues, such as thrombolytic therapy for patients with cardiopulmonary resuscitation or previous stroke, use of coronary artery bypass surgery and the effect of operator experience on angioplasty success rate, has also been made possible. The major accomplishments as well as the deficiencies of the current approach to patient management after thrombolysis are reviewed, and the new TAMI trials currently underway are discussed.
Asunto(s)
Angioplastia de Balón , Infarto del Miocardio/terapia , Activador de Tejido Plasminógeno/administración & dosificación , Trastornos Cerebrovasculares/complicaciones , Ensayos Clínicos como Asunto , Terapia Combinada , Enfermedad Coronaria/etiología , Estudios de Evaluación como Asunto , Humanos , Infusiones Intravenosas , Estudios Multicéntricos como Asunto , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/mortalidad , Recurrencia , Factores Sexuales , Volumen SistólicoRESUMEN
To evaluate the potential benefit of MDL 17043, a new inotrope-vasodilator agent, in the short- and long-term management of severe heart failure, its hemodynamic effects were determined after both intravenous (cumulative average dose 3.7 mg/kg) and oral (average 18.4 mg/kg) administration in 38 patients with severe intractable heart failure. After both intravenous and oral therapy, cardiac index increased from a control value of 2.1 +/- 0.4 to 3.6 +/- 0.9 liters/min per m2, p less than 0.001 (intravenous) and from 2.2 +/- 0.5 to 3.4 +/- 0.6 liters/min per m2, p less than 0.001 (oral). Pulmonary capillary wedge pressure decreased from 26 +/- 6 to 14 +/- 7 mm Hg (p less than 0.001) and from 26 +/- 7 to 18 +/- 8 mm Hg (p less than 0.001) after intravenous and oral routes, respectively. Stroke volume index and stroke work index increased, and right atrial and pulmonary arterial pressures and systemic vascular resistance decreased by similar magnitude after both intravenous and oral MDL 17043 (all p less than 0.001). The hemodynamic effects persisted during 4 hours of observation. Thirty-seven patients were discharged while receiving MDL 17043 therapy and were followed up for a mean of 5.6 months (range 0.5 to 13). Thirty-three of the 37 patients had short-term improvement clinically by at least one New York Heart Association functional class. Undesirable effects, including nausea (35%), anorexia (27%), fluid retention (24%) and thrombocytopenia (less than 1%), necessitated discontinuation of therapy in 11 patients (30%) who were receiving multiple drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Cardiotónicos/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Imidazoles/administración & dosificación , Administración Oral , Anciano , Presión Sanguínea/efectos de los fármacos , Cardiotónicos/efectos adversos , Cardiotónicos/farmacología , Cardiotónicos/uso terapéutico , Enoximona , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Imidazoles/efectos adversos , Imidazoles/farmacología , Imidazoles/uso terapéutico , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Presión Esfenoidal Pulmonar/efectos de los fármacos , Volumen Sistólico/efectos de los fármacos , Trombocitopenia/inducido químicamente , Resistencia Vascular/efectos de los fármacosRESUMEN
OBJECTIVES: We investigated the hypothesis that abciximab might lead to a differential effect among patients with different lesion morphologies; hence, its cost/benefit ratio would be optimized if it were used selectively on the basis of baseline angiographic findings. BACKGROUND: Major complications of coronary angioplasty occur in 4% to 9% of patients. In the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) and Evaluation of PTCA To Improve Long-term Outcome with abciximab GPIIb/IIIa Receptor Blockade (EPILOG) trials, abciximab decreased the ischemic complications after intervention by 35% to 56%. However, the cost of this agent is appreciable, and there remain concerns about the safety of its readministration. METHODS: There were 1,362 patients in EPIC and 2,792 patients in EPILOG randomized to either bolus plus an infusion of abciximab or placebo, administered with aspirin and heparin at the time of the coronary intervention. Data from these studies were combined, and a differential effect of abciximab in relation to baseline lesion morphology on 30-day risk of death, myocardial infarction or urgent intervention was investigated using the Breslow Day test for statistical interaction. RESULTS: Abciximab consistently reduced the relative risk of complications across all lesion morphologies studied, with the possible exception of patients treated with degenerated saphenous vein grafts (risk with placebo 16.3% vs. risk with abciximab 18.6%, Breslow Day test for interaction, p=0.08). However, the absolute reduction of risk was somewhat greater in patients with more complex B2 or C lesions (7.6% and 5.8%, respectively) than in patients with morphologically simpler A or B1 lesions (3.7% and 3.2%, respectively). CONCLUSIONS: The reduction of early adverse ischemic events associated with angioplasty by abciximab occurs largely independent of pretreatment morphology.
Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Isquemia Miocárdica/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Abciximab , Anciano , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Resultado del TratamientoRESUMEN
To evaluate changes in myocardial energetics and systemic and cardiac sympathetic activity associated with improved left ventricular function after MDL 17043, a new inotropic vasodilator agent, systemic and coronary hemodynamics and myocardial catecholamine balance were determined in 17 patients with severe heart failure. After the administration of MDL 17043, cardiac index increased by 67% and pulmonary capillary wedge pressure decreased (25 +/- 5 to 14 +/- 7 mm Hg, p less than 0.01), indicating improved left ventricular function. Coronary sinus blood flow (75 +/- 29 to 111 +/- 51 ml/min, p less than 0.01) and myocardial oxygen consumption (9.9 +/- 3.3 to 11.8 +/- 5.4 ml/min, p less than 0.05) increased despite decreased myocardial oxygen extraction (11.7 +/- 2 to 10.1 +/- 3.3 vol%, p less than 0.05) and a higher coronary sinus oxygen content. Although transmyocardial lactate extraction remained unchanged, increased myocardial oxygen consumption has potential deleterious effects on myocardial metabolic function. Arterial norepinephrine concentrations and transmyocardial norepinephrine release also remained unchanged. These findings suggest that MDL 17043 improves left ventricular pump function, but produces no detectable change in systemic and cardiac sympathetic activity. Improved left ventricular function is associated with increased myocardial oxygen consumption despite primary coronary vasodilation.
Asunto(s)
Cardiotónicos/uso terapéutico , Catecolaminas/metabolismo , Insuficiencia Cardíaca/fisiopatología , Hemodinámica/efectos de los fármacos , Imidazoles/uso terapéutico , Vasodilatadores/uso terapéutico , Adulto , Anciano , Cardiotónicos/farmacología , Circulación Coronaria/efectos de los fármacos , Enoximona , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Humanos , Imidazoles/farmacología , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
The influence of infarct location on arterial patency, left ventricular function and mortality after 150 mg of intravenous recombinant tissue-type plasminogen activator (rt-PA) and selective coronary angioplasty was studied in 386 patients with acute myocardial infarction. In 329 patients with acute and 1 week angiograms, the 90 min infarct-related artery patency rate after rt-PA in the left anterior descending, the left circumflex and the right coronary artery was 77, 68 and 68%, respectively. Angioplasty, performed in half the patients, resulted in a final acute patency rate of 93%, which was not related to arterial distribution. Repeat catheterization and revascularization were required in 12% of patients before day 7 and were independent of arterial distribution. The reocclusion rate for the right coronary artery (21%) was higher than that for the left anterior descending (12%) or left circumflex (5%) artery (p = 0.01). Acute and 1 week contrast ventriculograms suitable for analysis were available in 266 patients. Whereas serial left ventricular ejection fraction did not improve during the course of this study, serial regional wall motion (centerline chord method) improved in each arterial distribution. The in-hospital mortality rate of 6% was not related to arterial distribution, although death was twice as likely with proximal compared with distal lesions. Ten of 11 patients who died in the group with the left anterior descending artery as the infarct-related artery had a lesion proximal to the first septal perforator branch.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Angioplastia de Balón , Fibrinolíticos/uso terapéutico , Infarto del Miocardio/terapia , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Ensayos Clínicos como Asunto , Vasos Coronarios/fisiopatología , Corazón/fisiopatología , Cardiopatías/etiología , Ventrículos Cardíacos , Humanos , Mortalidad , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocardio/patología , Grado de Desobstrucción VascularRESUMEN
The influence of multiple clinical, angiographic and technical variables on the outcome of percutaneous transluminal coronary angioplasty was evaluated in a group of 76 consecutive patients with total coronary artery occlusion. Angioplasty was performed successfully in 53% of these patients. The likelihood of successful angioplasty was favorably influenced by: 1) a history of prior myocardial infarction in the distribution of the occluded arterial segment (p = 0.03); 2) an estimated maximal duration of arterial occlusion of less than 20 weeks (p less than 0.001); and 3) a length of nonvisualized arterial segment distal to the point of occlusion of less than 1.5 cm (p = 0.03). The outcome of coronary angioplasty was not significantly influenced by the vessel involved, the location of the occlusion within an involved vessel, the morphology of the occlusion (tapered versus abrupt) or the age and sex of the patient. There were no deaths and no vascular perforations. Four patients had recurrent coronary occlusion within 24 hours of the procedure; in three of these, recurrent occlusion was successfully treated with reangioplasty and in one, emergent surgical revascularization was performed. Embolic occlusion of an arterial branch distal to the point of total coronary occlusion occurred in 4 of the 40 successfully recanalized arteries. Seventy-five percent of patients having successful recanalization of an occluded coronary artery were free of the anginal symptoms that had prompted performance of the procedure at a mean follow-up period of 7.3 months. Thus, angioplasty of a total coronary artery occlusion can be performed safely and effectively, particularly in patients with a history of prior myocardial infarction, a brief estimated duration of coronary occlusion and a short nonvisualized occluded arterial segment.
Asunto(s)
Angioplastia de Balón , Arteriopatías Oclusivas/terapia , Enfermedad Coronaria/terapia , Adulto , Factores de Edad , Anciano , Angiografía Coronaria , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Factores Sexuales , Factores de TiempoRESUMEN
The impact of associated precordial ST segment depression in inferior myocardial infarction on angiographic and clinical outcomes after thrombolytic therapy and selective coronary angioplasty was studied in 583 patients with acute myocardial infarction. Anterior infarction (Group I), inferior infarction with precordial ST segment depression (Group II) and inferior infarction without precordial ST segment depression (Group III) were present in 289, 135 and 159 patients, respectively. Precordial ST segment depression was more frequent in circumflex than right coronary infarct-related arteries (44 [71%] of 62 versus 91 [40%] of 230; p = 0.000). Although acute patency rates were not statistically different, there was a trend toward different patency rates at day 7 (Group I 88%, Group II 84%, Group III 80%; p = 0.089) partly because of insignificantly higher reocclusion rates in inferior infarction without precordial ST segment depression (Group I 11%, Group II 10%, Group III 18%, p = 0.104). Infarct zone regional wall motion (standard deviations/chord) in inferior infarction was lower with precordial ST segment depression, both acutely (Group I -2.8 +/- 0.9, Group II -2.5 +/- 1.2, Group III 2.0 +/- 1.1; p = 0.000) and at day 7 (Group I -2.2 +/- 1.1, Group II -2.3 +/- 1.1, Group III -1.9 +/- 1.3; p = 0.011). Precordial ST segment depression was associated with a lower ejection fraction in inferior infarction both acutely (Group I 47 +/- 11%, Group II 53 +/- 11%, Group III 58 +/- 9%; p = 0.000) and at day 7 (Group I 49 +/- 12%, Group II 53 +/- 10%, Group III 58 +/- 8%; p = 0.000). Complication rates tended to be higher in inferior infarction when precordial ST segment depression was present. Mortality rates for Groups I, II and III were 8%, 6% and 5%, respectively. These results suggest that precordial ST segment depression in inferior infarction predicts a worse ventriculographic and clinical outcome despite reperfusion therapy.
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Electrocardiografía , Infarto del Miocardio/mortalidad , Reperfusión Miocárdica , Angioplastia Coronaria con Balón , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Pronóstico , Estudios Prospectivos , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
OBJECTIVES: This study was undertaken to establish evidence for physiologic activity and to study the safety of murine-derived monoclonal antibody 7E3 Fab (m7E3 Fab) in patients receiving recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND: Platelet aggregation is believed to be a significant factor in the failure of pharmacologic reperfusion. By binding to the glycoprotein IIb/IIIa receptor, m7E3 Fab inhibits platelet aggregation and has been shown experimentally to decrease the time required for lysis and to prevent reocclusion. However, the safety of profound platelet inhibition after thrombolysis for acute myocardial infarction has not been tested in humans. METHODS: Sixty patients receiving rt-PA, aspirin and heparin for acute myocardial infarction received m7E3 Fab bolus injections in ascending doses at 3, 6 and 15 h after initiation of the thrombolytic infusion. Ten patients treated with rt-PA but not m7E3 Fab were studied as control subjects. RESULTS: Receptor site blockade and inhibition of platelet aggregation to 20 mumol/liter adenosine diphosphate were maximal at a dose of 0.25 mg/kg body weight of m7E3 Fab. Fifteen (25%) m7E3 Fab-treated patients and five (50%) control patients had major bleeding; eight of these events in seven m7E3 Fab-treated patients and one in a control patient occurred at the time of aortocoronary bypass surgery. Recurrent ischemia occurred in eight (13%) m7E3 Fab-treated patients and two (20%) control subjects. Coronary angiography was performed in 43 patients; the infarct-related coronary artery was patent in 5 of 9 (56%) control patients and 34 (92%) of 37 patients receiving m7E3 Fab. CONCLUSIONS: Profound inhibition of platelet aggregation after thrombolysis was associated with bleeding rates comparable to those in control patients and a low rate of recurrent ischemia. The combination of m7E3 Fab and rt-PA, heparin and aspirin appears to be a promising and safe combination that should be evaluated in further studies of patients with acute myocardial infarction.
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Anticuerpos Monoclonales/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Agregación Plaquetaria/efectos de los fármacos , Glicoproteínas de Membrana Plaquetaria/inmunología , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacología , Quimioterapia Combinada , Femenino , Hemorragia/inducido químicamente , Humanos , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Fragmentos Fab de Inmunoglobulinas/farmacología , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Proyectos Piloto , Glicoproteínas de Membrana Plaquetaria/efectos de los fármacos , Recurrencia , Trombocitopenia/inducido químicamente , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del TratamientoRESUMEN
To determine the clinical profile and efficacy of accelerated recombinant tissue-type plasminogen activator (rt-PA) dose regimens, five different strategies of thrombolytic therapy in a total of 232 patients were systematically evaluated in the setting of acute myocardial infarction. The fifth strategy involved a combination of accelerated rt-PA and intravenous urokinase (regimen E). A weight-adjusted dose of 1.25 mg/kg body weight of tissue plasminogen activator over 90 min (regimen C) yielded the highest coronary patency rate (83%) at acute angiography. The associated in-hospital reocclusion rate for this regimen was low (4%). An exaggerated (60-min) dosage regimen yielded an inferior coronary patency rate (63%). Combination therapy (regimen E) was associated with a 72% patency rate and 3% reocclusion rate. Marginal improvement in global ejection fraction and regional wall function was demonstrated with all strategies by predischarge catheterization. Bleeding complications were most common at the periaccess site and were not different from those in previous experiences reported with conventional 3-h dosing regimens. Measurements of baseline, 30-min and 3-h levels of tissue plasminogen activator, fibrinogen and fibrin(ogen) degradation products were obtained. At 3 h, fibrinogen levels of less than 1 g/liter were demonstrated with combination therapy (regimen E) as well as with regimen C. Major clinical outcomes including death, reocclusion and reinfarction also showed a tendency to be less common with regimen C. Therefore, although accelerated dose regimens of rt-PA do not reliably yield acute coronary patency rates greater than 85%, an acute coronary patency rate of approximately 85% can be approached.(ABSTRACT TRUNCATED AT 250 WORDS)
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Infarto del Miocardio/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Grado de Desobstrucción Vascular/efectos de los fármacos , Adulto , Anciano , Quimioterapia Combinada , Femenino , Fibrinógeno/análisis , Hemorragia/etiología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/sangre , Proteínas Recombinantes/farmacología , Recurrencia , Factores de Tiempo , Activador de Tejido Plasminógeno/sangre , Activador de Tejido Plasminógeno/farmacología , Resultado del Tratamiento , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Activador de Plasminógeno de Tipo Uroquinasa/farmacología , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéutico , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
OBJECTIVES: The aim of this study was to assess the hemorrhagic risk associated with fibrin-specific thrombolytic therapy and invasive procedures with acute myocardial infarction. BACKGROUND: Successful coronary artery reperfusion has important prognostic implications. Because immediate coronary angiography is the only method proved to differentiate early fibrinolytic success from failure, its use may be important for selected patients. METHODS: Five hundred seventy-five patients were evaluated with six combined thrombolytic and catheterization strategies. Patients were randomized to intravenous urokinase alone, recombinant tissue-type plasminogen activator (rt-PA) alone, or both; simultaneously they were randomized to an immediate versus a deferred catheterization strategy. Hemorrhagic events were assessed. The correlation of hemorrhage with clinical and hemostatic variables was evaluated. Prespecified transfusion criteria were employed. RESULTS: No difference in baseline characteristics or in hemorrhagic complications was noted among the three thrombolytic regimens. Although mild (< 250 ml) bleeding was more common in the group with immediate catheterization, no clinically significant difference among catheterization groups was seen in moderate to life-threatening hemorrhagic events. Most bleeding occurred at vascular access sites, yet severe and life-threatening hemorrhage occurred in < 1% of patients. Baseline and nadir fibrinogen levels, change in baseline fibrinogen levels and peak fibrin and fibrinogen degradation products did not correlate with bleeding risk. A clinical predisposition for bleeding was observed in women as well as older (> or = 65 years) and lighter (< or = 70 kg) patients. With prespecified transfusion criteria, only a minimal increase in blood product usage was noted with immediate catheterization. CONCLUSIONS: Immediate cardiac catheterization can be accomplished without a clinically significant difference in bleeding risk. Fibrin specificity offers no clear advantage in reducing hemorrhagic risk. Bleeding risk correlates best with baseline patient characteristics. Finally, the amount of blood transfused can be reduced with lower transfusion criteria.
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Cateterismo Cardíaco/efectos adversos , Fibrina/efectos de los fármacos , Hemorragia/etiología , Infarto del Miocardio/terapia , Terapia Trombolítica/efectos adversos , Femenino , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéuticoRESUMEN
OBJECTIVES: This study was designed to assess outcome in patients with diabetes who received thrombolytic therapy and to determine whether differences in angiographic characteristics may account for the worse outcome observed in diabetic patients. BACKGROUND: Patients with diabetes are known to have a worse outcome after acute myocardial infarction than that of patients without diabetes. METHODS: Clinical and angiographic characteristics of the 148 patients with diabetes and the 923 patients without diabetes in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials were examined and analyzed. RESULTS: Patients with diabetes tended to be older (median age 59 vs. 56 years) and to have a higher incidence of hypertension and hyperlipidemia and a lower incidence of cigarette smoking. Patients with diabetes had significantly more severe anatomic disease (66% vs. 46% had multivessel disease, p < 0.0001), similar global left ventricular ejection fraction (49% vs. 51%) and worse noninfarct zone ventricular function (-0.13 vs. 0.32 SD/chord, p = 0.02) than that of nondiabetic patients. Angiographic patency rates at 90 min after thrombolytic therapy were similar in patients with and without diabetes (initial 90-min patency 71% vs. 70%). Diabetic patients had nearly twice the in-hospital mortality rate (11% vs. 6%, p < 0.02) and a higher incidence of pulmonary edema (11% vs. 4%, p = 0.001). Diabetic women had an especially high in-hospital mortality rate (21%). No retinal hemorrhages were observed. Although diabetes as an unadjusted variable was predictive of in-hospital (p < 0.02) and long-term (p = 0.003) mortality, after adjustment for baseline clinical and angiographic characteristics, diabetes was not found to have an independent influence on mortality. CONCLUSIONS: Patients with diabetes after myocardial infarction have a worse outcome than that of patients without diabetes despite similar rates of infarct vessel patency. However, diabetes was not found to be an independent risk factor for increased mortality. These findings suggest that diabetes itself is not a major risk factor for poor early outcome after thrombolytic therapy for myocardial infarction; rather, the secondary effects such as more extensive coronary artery disease account for the worse outcome.
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Complicaciones de la Diabetes , Infarto del Miocardio/terapia , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéutico , Anciano , Angioplastia Coronaria con Balón , Cateterismo Cardíaco , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/patología , Enfermedad Coronaria/fisiopatología , Vasos Coronarios/patología , Vasos Coronarios/fisiopatología , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Volumen Sistólico , Análisis de Supervivencia , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
This study sought to determine whether clinical variables can be used to identify patients at high risk of recurrent spontaneous myocardial ischemia or hemodynamic compromise during the 1st 4 days after intravenous thrombolysis for acute myocardial infarction. Of 288 patients randomly assigned to a conservative postthrombolysis strategy, 54 (19%) required urgent cardiac catheterization within 24 h; 75 (26%) underwent urgent cardiac catheterization within 4 days of admission. Of the clinical variables examined by multiple logistic regression analysis, only patient age and anterior wall myocardial infarction correlated with the need for urgent cardiac catheterization (p = 0.0016 and p = 0.017, respectively). Compared with recombinant tissue-type plasminogen activator or urokinase monotherapy, combination therapy with these agents was associated with a lower need for acute intervention during the 1st 24 h after admission, but the difference did not reach statistical significance (14% for combination therapy vs. 21% for each agent alone, p = 0.30). Of the 75 patients undergoing urgent coronary angiography, only 39% had an occluded infarct-related artery. Emergency coronary angioplasty was performed in 49% of the patients and coronary artery bypass graft surgery was performed urgently in 3%. Despite these interventions, the need for urgent cardiac catheterization was associated with an in-hospital mortality rate of 7% (vs. 3% in the group not requiring urgent angiography, p = 0.36); mean left ventricular ejection fraction was 50.5 +/- 11% (vs. 54.3 +/- 10.8%, p = 0.12) and regional infarct zone wall motion was -2.68 +/- 1.07 SD/chord (vs. -2.46 +/- 1.19 SD/chord; p = 0.44).(ABSTRACT TRUNCATED AT 250 WORDS)