RESUMEN
Atherosclerotic plaques form at specific sites of the arterial tree, an observation that has led to the "geometric risk factor" hypothesis for atherogenesis. It is accepted that the location of atherosclerotic plaques is correlated with sites subjected to low abnormal values of wall shear stress (WSS), which is in turn determined by the specific geometry of the arterial segment. In particular, the left coronary artery (LCA) is one of the most important sites of plaque formation and its progression may lead to stroke. However, little is known about hemodynamics and WSS distributions in the LCA. The purpose of this work is to set up a method to evaluate flow patterns and WSS distributions in the human LCA based on real patient-specific geometries reconstructed from medical images.
Asunto(s)
Arterias/fisiopatología , Vasos Coronarios/fisiopatología , Estrés Fisiológico , Aterosclerosis/fisiopatología , Humanos , Modelos AnatómicosRESUMEN
OBJECTIVE: To assess whether sex differences exist in the angiographic severity, management and outcomes of acute coronary syndromes (ACS). METHODS: The study comprised 7638 women and 19 117 men with ACS who underwent coronary angiography and were included in GRACE (Global Registry of Acute Coronary Events) from 1999-2006. Normal vessels/mild disease was defined as <50% stenosis in all epicardial vessels; advanced disease was defined as >or=one vessel with >or=50% stenosis. RESULTS: Women were older than men and had higher rates of cardiovascular risk factors. Men and women presented equally with chest pain; however, jaw pain and nausea were more frequent among women. Women were more likely to have normal/mild disease (12% vs 6%, p<0.001) and less likely to have left-main and three-vessel disease (27% vs 32%, p<0.001) or undergo percutaneous coronary intervention (65% vs 68%, p<0.001). Women and men with normal and mild disease were treated less aggressively than those with advanced disease. Women with advanced disease had a higher risk of death (4% vs 3%, p<0.01). After adjustment for age and extent of disease, women were more likely to have adverse outcomes (death, myocardial infarction, stroke and rehospitalisation) at six months compared to men (odds ratio 1.24, 95% confidence interval 1.14 to 1.34); however, sex differences in mortality were no longer statistically significant. CONCLUSIONS: Women with ACS were more likely to have cardiovascular disease risk factors and atypical symptoms such as nausea compared with men, but were more likely to have normal/mild angiographic coronary artery disease. Further study regarding sex differences related to disease severity is warranted.
Asunto(s)
Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/mortalidad , Antagonistas Adrenérgicos beta/uso terapéutico , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Angiografía Coronaria , Femenino , Mortalidad Hospitalaria , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Sistema de Registros , Factores Sexuales , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To determine whether revascularisation is more likely to be performed in higher-risk patients and whether the findings are influenced by hospitals adopting more or less aggressive revascularisation strategies. METHODS: GRACE (Global Registry of Acute Coronary Events) is a multinational, observational cohort study. This study involved 24,189 patients enrolled at 73 hospitals with on-site angiographic facilities. RESULTS: Overall, 32.5% of patients with a non-ST elevation acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI; 53.7% in ST segment elevation myocardial infarction (STEMI)) and 7.2% underwent coronary artery bypass grafting (CABG; 4.0% in STEMI). The cumulative rate of in-hospital death rose correspondingly with the GRACE risk score (variables: age, Killip class, systolic blood pressure, ST segment deviation, cardiac arrest at admission, serum creatinine, raised cardiac markers, heart rate), from 1.2% in low-risk to 3.3% in medium-risk and 13.0% in high-risk patients (c statistic = 0.83). PCI procedures were more likely to be performed in low- (40% non-STEMI, 60% STEMI) than medium- (35%, 54%) or high-risk patients (25%, 41%). No such gradient was apparent for patients undergoing CABG. These findings were seen in STEMI and non-ST elevation ACS, in all geographical regions and irrespective of whether hospitals adopted low (4.2-33.7%, n = 7210 observations), medium (35.7-51.4%, n = 7913 observations) or high rates (52.6-77.0%, n = 8942 observations) of intervention. CONCLUSIONS: A risk-averse strategy to angiography appears to be widely adopted. Proceeding to PCI relates to referral practice and angiographic findings rather than the patient's risk status. Systematic and accurate risk stratification may allow higher-risk patients to be selected for revascularisation procedures, in contrast to current international practice.
Asunto(s)
Enfermedad Coronaria/cirugía , Revascularización Miocárdica , Selección de Paciente , Anciano , Angioplastia Coronaria con Balón , Estudios de Cohortes , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Recurrencia , Sistema de Registros , Medición de Riesgo/métodos , Resultado del TratamientoRESUMEN
Cardiovascular diseases account for 20% of deaths worldwide, rising to 50% in developed countries. Current understanding of atherosclerosis derives from a combination of research in animals and cell cultures, analysis of human lesions, clinical investigations of patients with acute coronary syndromes and epidemiological studies of coronary artery disease. By measuring serologic titers in the serum of patients after cardiovascular events, it was observed that the greater the infectious exposure of a patient, the larger the atherosclerotic lesion extension. In addition, gene targeting or pharmacological inhibition of certain cytokines aggravates atherosclerosis in animal experiments. Other animal experiments have succeeded in proving that B cells play a protective role in atherosclerosis through induced immunity against oxidized low-density lipoprotein and other epitopes. Molecular mimicry might respond to the question of how infection may trigger vulnerability in previously stable atherosclerotic lesions. The FLU Vaccination Acute Coronary Syndromes trial enhanced the debate on atherosclerosis prevention by the application of antiflu vaccine. So far, antibiotics have failed to reduce cardiovascular risk, as recent trials could not demonstrate a statistically significant risk reduction. Having assumed atherosclerosis to be an inflammatory disease, the WHO considered the possible role of secondary prevention with antiflu vaccine.
Asunto(s)
Aterosclerosis/inmunología , Inmunidad Innata , Infecciones/inmunología , Animales , Aterosclerosis/etiología , Aterosclerosis/virología , Humanos , Infecciones/complicaciones , Infecciones/virología , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/complicaciones , Gripe Humana/prevención & controlRESUMEN
OBJECTIVE: To determine whether creatinine clearance at the time of hospital admission is an independent predictor of hospital mortality and adverse outcomes in patients with acute coronary syndromes (ACS). DESIGN: A prospective multicentre observational study, GRACE (global registry of acute coronary events), of patients with the full spectrum of ACS. SETTING: Ninety four hospitals of varying size and capability in 14 countries across four continents. PATIENTS: 11 774 patients hospitalised with ACS, including ST and non-ST segment elevation acute myocardial infarction and unstable angina. MAIN OUTCOME MEASURES: Demographic and clinical characteristics, medication use, and in-hospital outcomes were compared for patients with creatinine clearance rates of > 60 ml/min (normal and minimally impaired renal function), 30-60 ml/min (moderate renal dysfunction), and < 30 ml/min (severe renal dysfunction). RESULTS: Patients with moderate or severe renal dysfunction were older, were more likely to be women, and presented to participating hospitals with more comorbidities than those with normal or minimally impaired renal function. In comparison with patients with normal or minimally impaired renal function, patients with moderate renal dysfunction were twice as likely to die (odds ratio 2.09, 95% confidence interval 1.55 to 2.81) and those with severe renal dysfunction almost four times more likely to die (odds ratio 3.71, 95% confidence interval 2.57 to 5.37) after adjustment for other potentially confounding variables. The risk of major bleeding episodes increased as renal function worsened. CONCLUSION: In patients with ACS, creatinine clearance is an important independent predictor of hospital death and major bleeding. These data reinforce the importance of increased surveillance efforts and use of targeted intervention strategies in patients with acute coronary disease complicated by renal dysfunction.
Asunto(s)
Angina Inestable/mortalidad , Creatinina/metabolismo , Infarto del Miocardio/mortalidad , Adulto , Anciano , Angina Inestable/sangre , Angina Inestable/tratamiento farmacológico , Biomarcadores , Femenino , Hemorragia/mortalidad , Mortalidad Hospitalaria , Humanos , Enfermedades Renales/mortalidad , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/tratamiento farmacológico , Estudios Prospectivos , Accidente Cerebrovascular/mortalidad , SíndromeRESUMEN
AIMS: To compare management and clinical outcomes in hospitals stratified by the availability of on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with lanoteplase for acute myocardial infarction. METHODS AND RESULTS: We studied 15,078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h, 25% day-only, and 44% no on-site catheterization facilities. Rates of cardiac angiography (57%, 38%, 26%) and revascularization (37%, 21%, 17%) were higher in hospitals with increasing access to on-site facilities(P<0.0001). The presence of a 24-h on-site facility was the strongest predictor of angiography during the index admission (odds ratio 4.17, 95% CI 3.85-4.54). There were no major differences in patient outcomes at 30 days when hospitals were stratified by availability of on-site catheterization. Adjusted 1-year mortality was similar between groups of hospitals (odds ratio for day-only 0.94 [0.80-1.09] and odds ratio for no availability 0.95 [0.83-1.10] compared to hospitals with 24-h facilities). CONCLUSIONS: There is a marked variation in procedure use by the availability of on-site catheterization with no major differences in patient outcomes. There is a need for additional randomized trials in the current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction.
Asunto(s)
Cateterismo Cardíaco , Electrocardiografía , Fibrinolíticos/uso terapéutico , Accesibilidad a los Servicios de Salud , Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , Admisión del Paciente , Adolescente , Adulto , Anciano , Procedimientos Quirúrgicos Cardíacos , Angiografía Coronaria , Recolección de Datos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Revascularización Miocárdica , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Reino Unido/epidemiologíaRESUMEN
AIMS: We examined the geographic variations in InTIME-II, a randomized double-blind trial comparing alteplase with lanoteplase for myocardial infarction. METHODS AND RESULTS: We compared baseline characteristics, management, and outcomes in four regions (Western Europe, Eastern Europe, North America, and Latin America) and in countries with historically different management approaches (Germany vs the U.K., the U.S. vs Canada). Thirty-day mortality in Western Europe, Eastern Europe, North America and Latin America was 6.7%, 7.3%, 5.7%, 10.1%, P<0.0001. Adjusted mortality for Europe was intermediate between North America and Latin America (odds ratios (OR) [95% confidence intervals (CI)] compared to Western Europe: North America 0.84 [0.67-1.0], Eastern Europe 1.2 [1.0-1.4], and Latin America 1.8 [1.3-2.7]). Revascularization rates varied 10-fold but did not explain regional mortality differences. Germany and the U.K. had similar adjusted 1-year mortality (OR for the U.K. 1.16 [0.92-1.5]), although invasive procedures were four- to 10-fold more common in Germany. Similarly the U.S. and Canada had equal adjusted 1-year mortality (OR for Canada 0.85 [0.61-1.17]) despite three-fold higher use of invasive procedures in the U.S. CONCLUSIONS: Significant geographic variations in practice and adjusted mortality following fibrinolysis persist despite recent guidelines. These findings have important implications in the design and interpretation of international studies, identify under- and over-utilized therapies, and support further study of treatments with marked worldwide variations.
Asunto(s)
Fibrinolíticos/uso terapéutico , Geografía , Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Procedimientos Quirúrgicos Cardíacos/estadística & datos numéricos , Recolección de Datos , Método Doble Ciego , Electrocardiografía , Determinación de Punto Final , Europa (Continente)/epidemiología , Europa Oriental/epidemiología , Femenino , Estudios de Seguimiento , Hospitales , Humanos , Hipolipemiantes/uso terapéutico , América Latina/epidemiología , Masculino , Persona de Mediana Edad , América del Norte/epidemiología , Pacientes , Receptores de Angiotensina/uso terapéutico , Resultado del TratamientoAsunto(s)
Angina Inestable/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Enoxaparina/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Anciano , Distribución de Chi-Cuadrado , Femenino , Heparina/uso terapéutico , Humanos , Masculino , Revascularización Miocárdica , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
BACKGROUND: We studied whether the level of anti-skeletal muscle glycolipid antibodies (AGA), a marker of acute rejection in heart transplantation, may be associated with an adverse prognosis in unstable angina. METHODS AND RESULTS: The in-hospital evolution of 50 patients with unstable angina (Braunwald class III B) was assessed. We determined the incidence of death, myocardial infarction, and refractory angina. Blood was collected at admission and 24 hours later for determination of AGA levels by enzyme-linked immunosorbent assay. Twenty-three patients showed a decrease in the AGA level at 24 hours after admission. Ten in-hospital cardiac events occurred in these patients (43.4%) as compared with 4 (14.8%) in the 27 patients who did not show a decrease (P =.025). In patients with previous myocardial infarction (n = 26), the AGA assay was a powerful predictor of outcome. In this subgroup, 66.6% of patients who had decreased AGA levels (8 of 12) had cardiac events as compared with 14.2% (2 of 14) of those who did not have that decrease (P =.001). CONCLUSIONS: We conclude that a decrease of AGA levels 24 hours after admission is associated with a complicated in-hospital course. This finding may provide new insights in the phenomenon of plaque instability involved in the development of acute coronary syndromes.
Asunto(s)
Angina Inestable/inmunología , Autoanticuerpos/sangre , Glucolípidos/inmunología , Músculo Esquelético/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Angina Inestable/sangre , Biomarcadores/sangre , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: The aim of this article was to investigate whether prior aspirin use in patients with acute coronary syndromes affects clinical outcome. The Efficacy Safety Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials have shown superiority of enoxaparin over unfractionated heparin (UFH) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the treatment effect of enoxaparin in the subset of patients reporting prior aspirin use has not been determined. METHODS: The rate of death, myocardial infarction, and urgent revascularization at days 8 and 43 after randomization was compared among patients who received aspirin within the week before randomization with those who did not receive aspirin in the TIMI 11B trial. A total of 3275 patients (84%) were prior aspirin users. RESULTS: The admission diagnosis was similar for prior and nonprior aspirin users. At both day 8 and day 43 the event rate was higher for prior aspirin users than for nonprior aspirin users (odds ratio 1.6 [1.24-2.08], P =.0004 at day 43), even after correction for baseline characteristics. Compared with those prior aspirin users taking UFH, enoxaparin-treated prior aspirin users had a reduced rate of the composite end point of death, myocardial infarction, and urgent revascularization at day 8 (odds ratio 0.82 [0.67-1.00], P =.046) and day 43 (odds ratio 0.83 [0.70-0.98], P =.032). CONCLUSION: Patients with UA/NSTEMI and prior aspirin use had a 60% higher risk of death and cardiac ischemic events compared with nonprior aspirin users. On the basis of this subanalysis, enoxaparin is superior to UFH in all patients. In prior aspirin users the benefit is more clearly demonstrated.
Asunto(s)
Angina Inestable/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Enoxaparina/uso terapéutico , Heparina/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Aspirina/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Medición de Riesgo , SíndromeRESUMEN
BACKGROUND: Two large-scale phase III clinical trials, the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) trial and the Thrombolysis in Myocardial Infarction (TIMI) 11B study, have shown the low-molecular-weight heparin, enoxaparin, to be more effective than unfractionated heparin (UFH) in reducing the risk of death and severe cardiac events in patients with rest unstable angina and/or non-ST-segment elevation myocardial infarction (NSTEMI). However, patients with NSTEMI acute coronary syndromes are a heterogeneous group. METHODS: A meta-analysis using pooled data from ESSENCE and TIMI 11B was performed to examine the efficacy of enoxaparin in different patient subgroups. In addition, a statistical model was developed to test which factors best predicted an enhanced treatment effect. RESULTS: Enoxaparin was more effective than intravenous dose-adjusted UFH in reducing the incidence of the composite endpoint (including death, myocardial infarction or recurrent angina prompting urgent revascularization) in the majority of subgroups at 43 days after randomization. Univariate analyses revealed that there was a greater benefit with enoxaparin in patients with ST-segment deviation or elevated cardiac enzyme markers on admission, women, nonsmokers and patients with characteristics indicative of higher cardiac risk, including prior percutaneous coronary interventions, being at least 65 years old, prior angina and prior aspirin use. Multivariate statistical modelling of treatment effect revealed that ST-segment depression and electrocardiographic changes were the best predictors of an enhanced treatment effect. CONCLUSIONS: These data reinforce previous evidence suggesting that enoxaparin administered subcutaneously twice daily may be considered as an alternative to intravenous UFH in the acute treatment of a broad range of patients with unstable coronary artery disease.
Asunto(s)
Angina Inestable/tratamiento farmacológico , Enoxaparina/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Adulto , Anciano , Angina Inestable/mortalidad , Ensayos Clínicos Fase III como Asunto , Electrocardiografía , Femenino , Heparina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Infarto del Miocardio/mortalidad , Oportunidad Relativa , Factores de Riesgo , Prevención Secundaria , Equivalencia Terapéutica , Resultado del TratamientoRESUMEN
Patients with acute myocardial infarction (AMI) who do not receive early reperfusion therapy are at high risk of reinfarction or death, and the efficacy and safety of antithrombotic therapy in this group of patients has not been evaluated. Enoxaparin is a low-molecular-weight heparin (LMWH) that has previously been shown to reduce the incidence of ischemic events in patients with unstable angina or non-Q-wave MI. The principal aims of the TETAMI study are to investigate the efficacy and safety of treatment with enoxaparin or tirofiban (a glycoprotein IIb/IIIa receptor antagonist) alone or in combination for 2 to 8 days in patients with AMI who are not eligible for early reperfusion therapy. In this 2 by 2 factorial design study approximately 900 patients will be randomly assigned, in a blinded manner, to one of four treatments: enoxaparin alone, enoxaparin plus tirofiban, unfractionated heparin (UFH), or UFH plus tirofiban, with appropriate matched placebos. The primary end point is the composite of death, recurrent AMI, and recurrent angina, analyzed at 30 days after AMI. The design and methods of the TETAMI study are described in this article.
Asunto(s)
Enoxaparina/administración & dosificación , Heparina/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Tirosina/análogos & derivados , Tirosina/administración & dosificación , Adulto , Anciano , Protocolos Clínicos , Quimioterapia Combinada , Enoxaparina/normas , Enoxaparina/toxicidad , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/normas , Fibrinolíticos/toxicidad , Heparina/normas , Heparina/toxicidad , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Placebos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Recurrencia , Tasa de Supervivencia , Tirofibán , Tirosina/normas , Tirosina/toxicidadRESUMEN
BACKGROUND: The rapid utilization of fibrinolytics following Q-wave myocardial infarction has clearly modified the evolution of this disease. However, it is still not known whether the immediate inhibition of platelet aggregation (PA) during the coronary event improves outcomes. HYPOTHESIS: The present study was designed to test, in patients with known coronary artery disease (chronic stable angina), whether the particular kinetic pattern of lysine acetylsalicylate (LA) compared with aspirin may affect the time to onset of inhibition of platelet aggregation. METHODS: Ten patients suffering from chronic stable angina participated in this study to compare the efficacy and speed of the inhibition of PA with 320 mg of LA versus 320 mg of aspirin. All patients discontinued the use of aspirin and any other anti-inflammatory agents for 15 days prior to the beginning of the study. They were randomly assigned to LA or aspirin. Blood specimens were obtained to measure the PA at admission, and 5, 10, 20, 30, and 60 min after ingestion. Patients continued to take the assigned drug once a day for the following 4 days. On Day 5, a new blood sample was taken. After this, patients underwent a 15-day wash-out period, and then crossed over to the opposite drug. The samples were analyzed immediately using platelet-rich plasma stimulated with adenosine diphosphate (ADP) 2 mumol/l, collagen 1 microgram/ml, epinephrine 20 mumol/l, and sodium arachidonate acid 0.75 mm/l. RESULTS: The same level of PA inhibition after 30 and 60 min of aspirin administration can be obtained with LA 5 min following ingestion (sodium arachidonate acid: LA: 16.3 +/- 25.9 vs. aspirin 57.6 +/- 8.2; p = 0.00014; collagen: LA 18.9 +/- 20.1 vs. aspirin 47.2 +/- 10.5; p = 0.00092; ADP: LA 27.3 +/- 18.4 vs. aspirin 39.7 +/- 21.8, p = 0.18; epinephrine: LA 22.0 +/- 9.9 vs. aspirin 55.4 +/- 10.9, p = 0.00002. CONCLUSIONS: Platelet aggregation inhibition immediately following LA may have significant clinical implications for the treatment of coronary syndromes.
Asunto(s)
Angina de Pecho/tratamiento farmacológico , Aspirina/análogos & derivados , Aspirina/farmacocinética , Lisina/análogos & derivados , Lisina/farmacocinética , Inhibidores de Agregación Plaquetaria/farmacocinética , Agregación Plaquetaria/efectos de los fármacos , Análisis de Varianza , Angina de Pecho/metabolismo , Angina de Pecho/fisiopatología , Aspirina/farmacología , Estudios Cruzados , Femenino , Humanos , Lisina/farmacología , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/farmacología , Método Simple Ciego , Factores de TiempoRESUMEN
BACKGROUND: Whether the clinical superiority of enoxaparin versus unfractionated heparin (UFH) depends on a more stable antithrombotic effect or the proportion of patients not reaching the therapeutic level with UFH has not been addressed. METHODS: All patients participating in the Thrombolysis In Myocardial Infarction 11B trial who received UFH and had sufficient activated partial thromboplastin time (aPTT) data (n = 1893) were compared with patients who received enoxaparin (n = 1938). Patients receiving UFH were divided into 3 categories depending on mean aPTT values throughout 48 hours: subtherapeutic, for those in whom the average aPTT fell below 55 seconds; therapeutic, between 55 and 85 seconds; and supratherapeutic, longer than 85 seconds. Events and bleeding rates were determined at 48 hours. RESULTS: A small portion of patients (6. 7%) had a subtherapeutic average aPTT value (n = 127). Forty-seven percent of patients (n = 891) fell within the therapeutic range, and 46% were in the supratherapeutic level (n = 875). Event rates were 7. 0% in the UFH group versus 5.4% with enoxaparin (P =.039). Events rates were higher in every aPTT strata compared with enoxaparin and statistically significant in the supratherapeutic group (odds ratio 0.65; 95% confidence interval, 0.47-0.89). Major bleeding rates were 0%, 0.6%, and 0.9% for the subtherapeutic, target, and supratherapeutic strata, respectively, and 0.8% with enoxaparin. Minor hemorrhages occurred in 5.1% of patients receiving enoxaparin versus 3.9%, 2%, and 2.3%, respectively, for the UFH subgroups (P <. 001 for all UFH groups vs enoxaparin). CONCLUSIONS: Enoxaparin showed a better clinical profile compared with every level of anticoagulation with UFH. Potential mechanisms for enoxaparin superiority are stable antithrombotic activity, lack of rebound thrombosis, and intrinsic superiority.
Asunto(s)
Angina Inestable/tratamiento farmacológico , Electrocardiografía , Enoxaparina/uso terapéutico , Fibrinolíticos/uso terapéutico , Heparina/análogos & derivados , Heparina/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Terapia Trombolítica , Anciano , Angina Inestable/sangre , Angina Inestable/fisiopatología , Método Doble Ciego , Electrocardiografía/efectos de los fármacos , Humanos , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Tiempo de Tromboplastina Parcial , Estudios Prospectivos , SeguridadRESUMEN
A subgroup meta-analysis from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) and the Thrombolysis in Myocardial Infarction (TIMI) 11B studies has shown that enoxaparin is superior to unfractionated heparin in reducing the composite end points of death, myocardial infarction, and emergency revascularization in patients with Q-wave myocardial infarction. The beneficial treatment effect was significant at 43 days.
Asunto(s)
Enoxaparina/uso terapéutico , Fibrinolíticos/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Anciano , Heparina/uso terapéutico , Humanos , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , Resultado del TratamientoRESUMEN
OBJECTIVES: We sought to determine whether the observed benefits of enoxaparin were maintained beyond the early phase; a one-year follow-up survey was undertaken for patients enrolled in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events (ESSENCE) study. BACKGROUND: We have previously reported a significant benefit of low molecular weight as compared with unfractionated heparin (UFH) in the 14- and 30-day incidence of a composite end point of death, myocardial infarction (MI) or recurrent angina in patients with unstable angina or non-Qwave MI. METHODS: The study recruited 3,171 patients with recent-onset rest angina and underlying ischemic heart disease. All patients received oral aspirin daily and were randomized to receive enoxaparin subcutaneously every 12 h or UFH (intravenous bolus followed by continuous infusion) in a double-blind, double-dummy fashion for a median of 2.6 days. RESULTS: The incidence of the composite triple end point at one year was lower among patients receiving enoxaparin as compared with those receiving UFH (32.0% vs. 35.7%, p = 0.022), with a trend toward a lower incidence of the secondary composite end point of death or MI (11.5% vs. 13.5%, p = 0.082). At one year, the need for diagnostic catheterization and coronary revascularization was lower in the enoxaparin group (55.8% vs. 59.4%, p = 0.036 and 35.9% vs. 41.2%, p = 0.002, respectively). CONCLUSIONS: In patients with unstable angina or non-Qwave MI, enoxaparin therapy significantly reduced the rates of recurrent ischemic events and invasive diagnostic and therapeutic procedures in the short term with sustained benefit at one year.
Asunto(s)
Angina Inestable/tratamiento farmacológico , Enoxaparina/uso terapéutico , Fibrinolíticos/uso terapéutico , Heparina/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Adulto , Anciano , Angina Inestable/complicaciones , Cateterismo Cardíaco/estadística & datos numéricos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Revascularización Miocárdica/estadística & datos numéricos , Prevención SecundariaRESUMEN
Large clinical trials provide invaluable information. This, combined with a number of small studies about the pathophysiology of certain diseases, permits us to re-consider previously accepted pathophysiological mechanisms and suggests an updated theory about the definition and diagnosis of individual diseases. This information obtained appears to place unstable angina in a new light. The instability of unstable angina seems to be the transient moment in which the previous clinical state is abandoned to pass into another clinical condition, rather than the establishment of a new diagnosis or nosological entity. Is this then the end of unstable angina as a final diagnosis?The development of troponin has increased our ability to identify myocardial necrosis. The myocardial ischemia leading to myocardial necrosis is the most important issue in atherosclerosis. In addition, immune cell activation may also relate to the extent of necrosis. The activation of the immune/inflammatory system in patients with acute coronary syndromes is probably not exactly related with the presence of an unstable plaque per se, as is usually inferred by inflammatory markers, but with the total atherosclerotic burden in the arterial tree of these patients. After all the new evidence of studies regarding coronary syndromes, is it not the time to reconsider the definition of unstable angina?
Asunto(s)
Angina Inestable/fisiopatología , HumanosRESUMEN
The role of infection in the instability of atherosclerotic plaques has been questioned because of discrepancies in the results of clinical trials that tested antibiotics in acute coronary syndromes. The results of the Randomized Trial of Roxithromycin in Non-Q-Wave Coronary Syndromes (ROXIS) are summarized and contrasted with two other pilot studies of antibiotic therapy of coronary artery disease. Relevant characteristics of patients enrolled and rationales for these trials are discussed and serologic results are presented.