RESUMEN
BACKGROUND: Although frailty is known to be an important prognostic factor in heart failure (HF), HF risk-adjustment models do not incorporate frailty measures and the interplay between frailty, age and pharmacotherapy is unclear. OBJECTIVES: To explore the relationships between frailty, pharmacotherapy and outcomes in heart failure (HF). METHODS: Retrospective cohort study of all adults in Alberta, Canada hospitalized for the first time for HF between 2004 and 2016. Frailty was defined using the Hospital Frailty Risk Score (HFRS). RESULTS: In 26 626 patients (mean age 77.4 years), the 8887 (33.4%) defined as frail (HFRS ≥ 5) were older, had higher Charlson scores and more prior emergency department visits or hospitalizations. The HFRS and the Charlson Score were only weakly correlated (r = 0.35). Whilst more common in older patients (41.4% of patients 80 or older), frailty was present in 22.4% of patients younger than 65. Frail patients had longer lengths of stay and worse outcomes postdischarge, but adding the HFRS to age, sex and Charlson score did not improve prediction of events (c-statistics 0.69 for 30-day mortality after admission, and 0.54 for 30-day readmission/ED visit/or death after discharge). Frail patients younger than 65 were significantly more likely than nonfrail patients 80 or older to be prescribed high-dose evidence-based HF therapies (27.1% vs. 22.2%, P = 0.003). CONCLUSION: Although the HFRS reflects aspects of frailty that patient age and Charlson scores do not, the addition of the HFRS to standard risk prediction equations provides little additional information. Prescribing practices correlate more with patient age than frailty status.
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Fragilidad/clasificación , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Anciano , Anciano de 80 o más Años , Alberta , Comorbilidad , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: Assess the risk of ischaemic events associated with psychosocial stress in patients with stable coronary heart disease (CHD). METHODS: Psychosocial stress was assessed by a questionnaire in 14 577 patients (median age 65.0, IQR 59, 71; 81.6% males) with stable CHD on optimal secondary preventive therapy in the prospective randomized STABILITY clinical trial. Adjusted Cox regression models were used to assess associations between individual stressors, baseline cardiovascular risk factors and outcomes. RESULTS: After 3.7 years of follow-up, depressive symptoms, loss of interest and financial stress were associated with increased risk (hazard ratio, 95% confidence interval) of CV death (1.21, 1.09-1.34; 1.15, 1.05-1.27; and 1.19, 1.08-1.30, respectively) and the primary composite end-point of CV death, nonfatal MI or nonfatal stroke (1.21, 1.13-1.30; 1.19, 1.11-1.27; and 1.17, 1.10-1.24, respectively). Living alone was related to higher risk of CV death (1.68, 1.38-2.05) and the primary composite end-point (1.28, 1.11-1.48), whereas being married as compared with being widowed, was associated with lower risk of CV death (0.64, 0.49-0.82) and the primary composite end-point (0.81, 0.67-0.97). CONCLUSIONS: Psychosocial stress, such as depressive symptoms, loss of interest, living alone and financial stress, were associated with increased CV mortality in patients with stable CHD despite optimal medical secondary prevention treatment. Secondary prevention of CHD should therefore focus also on psychosocial issues both in clinical management and in future clinical trials.
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Enfermedad Coronaria , Relaciones Interpersonales , Infarto del Miocardio/epidemiología , Estrés Psicológico , Accidente Cerebrovascular/epidemiología , Anciano , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/psicología , Depresión/diagnóstico , Depresión/epidemiología , Femenino , Humanos , Soledad , Masculino , Estado Civil , Persona de Mediana Edad , Psicología , Medición de Riesgo/métodos , Factores de Riesgo , Estadística como Asunto , Estrés Psicológico/diagnóstico , Estrés Psicológico/epidemiología , Estrés Psicológico/fisiopatología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).
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Disnea/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Natriuréticos/uso terapéutico , Péptido Natriurético Encefálico/uso terapéutico , Readmisión del Paciente/estadística & datos numéricos , Enfermedad Aguda , Anciano , Método Doble Ciego , Disnea/etiología , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Humanos , Hipotensión/inducido químicamente , Análisis de Intención de Tratar , Enfermedades Renales/etiología , Masculino , Persona de Mediana Edad , Natriuréticos/efectos adversos , Péptido Natriurético Encefálico/efectos adversos , RecurrenciaRESUMEN
BACKGROUND: Spontaneous reperfusion (SR) in ST elevation myocardial infarction (STEMI) improves clinical outcome, yet its incidence and impact among diabetic patients is unclear. OBJECTIVE: To carry out a systematic analysis of SR in the diabetic cohort of a large primary percutaneous coronary intervention (PCI)-treated population with STEMI. METHODS AND RESULTS: 4944 patients (15.5% diabetic) undergoing primary PCI in the APEX AMI study were evaluated. SR defined as pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow occurred in 11.5% of patients; it was more common in non-diabetic (11.9%) than in diabetic patients (9.2%) (p = 0.028). Patients with SR versus no SR had improved post-PCI TIMI 3 flow: in non-diabetic patients (99.8% vs 90.3%, p<0.001) and in diabetic patients (98.6% vs 84.9%, p<0.001). Non-diabetic patients with SR showed a significant improvement in 90-day death/shock/congestive heart failure (CHF) compared with those without SR: 4.4% versus 8.9% (p = 0.001), respectively. The composite outcome in diabetic patients with versus without SR was 10.0% versus 14.9% (p = 0.270), respectively. When outcomes were examined according to tertiles of baseline blood glucose, both non-diabetic and diabetic patients with normoglycaemia showed higher SR rates (15.5%, 10.3%, 7.3% for non-diabetic patients, p<0.001; 17.4%, 7.2%, 9.1% for diabetic patients, p = 0.132), greater ST resolution (55.4%, 52.6%, 49.7% for non-diabetic patients, p = 0.030; 50%, 46.4%, 39.1% for diabetic patients, p = 0.179), and improved 90-day death/shock/CHF (5.2%, 8.3%, 14% for non-diabetic patients p<0.001; 8.7%, 4.2%, 15.8% for diabetic patients, p = 0.006). CONCLUSIONS: These data indicate that SR is less common in diabetic patients with STEMI. Diabetic patients without SR have worse post-PCI epicardial patency, which contributes to adverse outcomes. Diabetic patients with normal baseline blood glucose and SR have enhanced epicardial flow after PCI and improved prognosis.
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Angiopatías Diabéticas/terapia , Infarto del Miocardio/terapia , Reperfusión Miocárdica/métodos , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Angiografía Coronaria/métodos , Angiopatías Diabéticas/diagnóstico por imagen , Angiopatías Diabéticas/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/mortalidad , Reperfusión Miocárdica/mortalidad , Remisión Espontánea , Anticuerpos de Cadena Única , Resultado del Tratamiento , Vasodilatadores/uso terapéuticoRESUMEN
OBJECTIVE: To assess variables associated with the occurrence of atrial fibrillation (AF) and the relation of AF with short- and long-term outcomes and with other in-hospital complications in patients with acute coronary syndromes (ACS) with and without ST-segment elevation. DESIGN: Pooled database of 120 566 patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation (NSTE) ACS enrolled in 10 clinical trials. Multivariable logistic regression and Cox proportional hazards modelling were used to identify factors associated with AF and its relation with clinical outcomes. SETTING: ACS complicated by AF. PATIENTS: 120,566 patients with STEMI and NSTE-ACS in 10 clinical trials. INTERVENTIONS: None evaluated. MAIN OUTCOME MEASURE: Short- and long-term mortality. RESULTS: Occurrence of AF was 7.5% in the overall population (STEMI 8.0% (n = 84 161); NSTE-ACS = 6.4% (n = 36,405)). Seven-day mortality was higher for patients with AF (5.1%) than for those without (1.6%). After adjusting for confounders, association of AF with 7-day mortality was present in STEMI (hazards ratio (HR) = 1.65; 95% CI 1.44 to 1.90) and NSTE-ACS (HR = 2.30; 95% CI 1.83 to 2.90; p interaction = 0.015). Risk of long-term mortality (day 8 to 1 year) was also higher in STEMI (HR = 2.37; 95% CI 1.79 to 3.15) and NSTE-ACS (HR = 1.67; 95% CI 1.41 to 1.99). AF had a larger impact in NSTE-ACS on risk of short-term mortality (p<0.001), stroke (p<0.001), ischaemic stroke (p<0.001) and moderate or severe bleeding (p<0.001). CONCLUSIONS: AF is more common in patients with STEMI. An association of AF with short- and long-term mortality among patients with STEMI and NSTE-ACS was found. Understanding these findings may lead to better care of patients with this common arrhythmia.
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Síndrome Coronario Agudo/epidemiología , Fibrilación Atrial/epidemiología , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/fisiopatología , Factores de Edad , Anciano , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/fisiopatología , Electrocardiografía , Métodos Epidemiológicos , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/fisiopatología , PronósticoRESUMEN
OBJECTIVES: To examine the interaction between ST segment depression on the baseline ECG and subsequent in-hospital revascularisation on six month mortality among patients with non-ST elevation acute coronary syndromes. To examine whether ST segment depression influenced clinical decision making and whether there was international variation in the use of cardiac procedures across ST segment depression categories. METHODS: 11 453 patients enrolled in GUSTO-IIB (global use of strategies to open occluded coronary arteries), PARAGON (platelet IIb/IIIa antagonism for the reduction of acute coronary syndrome events in a global organisation network) -A, and PARAGON-B were studied. Patients were categorised as having no ST segment depression, 1 mm ST segment depression in two contiguous leads, and ST segment depression > or = 2 mm in two contiguous leads. International practice across four geographic regions was examined: USA, Canada, Europe, and Australia/New Zealand. RESULTS: Revascularisation appeared to have no impact on survival among patients with no ST segment depression; however, revascularisation was associated with a significant survival benefit among patients with ST segment depression > or = 1 mm. There was an inverse relation between the extent of ST segment depression and the use of angiography as well as angioplasty (p < 0.01). However, patients with ST segment depression > or = 2 mm were more likely to undergo bypass surgery. The only significant trend of increasing use of revascularisation procedures with increasing ST segment depression was observed in the USA. CONCLUSIONS: International practice patterns in procedure use appear to be insensitive to the extent of ST segment depression. Major opportunities for more efficient delivery of care exist in all regions.
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Enfermedad Coronaria/terapia , Reperfusión Miocárdica/métodos , Enfermedad Aguda , Anciano , Australasia , Canadá , Angiografía Coronaria/métodos , Puente de Arteria Coronaria/métodos , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/fisiopatología , Toma de Decisiones , Electrocardiografía/métodos , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/tendencias , Estudios Prospectivos , Factores de Riesgo , Análisis de Supervivencia , Síndrome , Estados UnidosRESUMEN
BACKGROUND: Unfractionated heparin is widely used in patients with non-ST-elevation acute coronary syndromes but has important limitations. Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed. OBJECTIVE: To investigate the efficacy and safety of a direct, selective factor Xa inhibitor, DX-9065a (Daiichi Pharmaceuticals LTD, Inc.) compared with heparin, in patients with non-ST-elevation acute coronary syndromes. PATIENTS AND METHODS: Patients (n = 402) from the USA, Canada, and Japan were randomized to blinded, weight-adjusted heparin, low-dose DX-9065a, or high-dose DX-9065a. RESULTS: The primary efficacy endpoint of death, myocardial infarction, urgent revascularization, or ischemia on continuous ST-segment monitoring occurred in 33.6%, 34.3%, and 31.3% of patients assigned to heparin, low-dose DX-9065a, and high-dose DX-9065a (P = 0.91 for heparin vs. combined DX-9065a). The composite of death, myocardial infarction, or urgent revascularization occurred in 19.5%, 19.3%, and 11.9% (P = 0.125 for heparin vs. high-dose DX-9065a) of patients; major or minor bleeding occurred in 7.7%, 4.2%, and 7.0% of patients; and major bleeding in 3.3%, 0.8%, and 0.9% of patients. Higher concentrations of DX-9065a were associated with a lower likelihood of ischemic events (P = 0.03) and a non-significant tendency toward a higher likelihood of major bleeding (P = 0.32). CONCLUSIONS: In this small phase II trial, there was a non-significant tendency toward a reduction in ischemic events and bleeding with DX-9065a compared with heparin in patients with acute coronary syndromes. The absence of an effect on ST-monitor ischemia warrants further investigation. These data provide the rationale for adequately powered studies of DX-9065a in acute coronary syndromes or percutaneous intervention.
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Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Inhibidores del Factor Xa , Serina Endopeptidasas/administración & dosificación , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/mortalidad , Relación Dosis-Respuesta a Droga , Electrocardiografía , Femenino , Hemorragia/inducido químicamente , Heparina/administración & dosificación , Heparina/toxicidad , Humanos , Isquemia/prevención & control , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Naftalenos/administración & dosificación , Naftalenos/toxicidad , Tiempo de Tromboplastina Parcial , Propionatos/administración & dosificación , Propionatos/toxicidad , Serina Endopeptidasas/uso terapéuticoRESUMEN
OBJECTIVES: To assess the impact of variation in prehospital care across distinct health care environments in ASSENT (assessment of the safety and efficacy of a new thrombolytic) -3 PLUS, a large (n = 1639) contemporary multicentred international trial of prehospital fibrinolysis. Specifically, the objectives were to assess predictors of time to treatment, whether components of time to treatment vary across countries, and the impact of physician presence before hospitalisation on time to treatment, adherence to protocol, and clinical events. METHODS: Patient characteristics associated with early treatment (< or = 2 hours), comparison of international variation in time to treatment, and components of delay were assessed. Trial specific patient data were linked with site specific survey responses. RESULTS: Younger age, slower heart rate, lower systolic blood pressure, and prior percutaneous coronary intervention were associated with early treatment. Country of origin accounted for the largest proportion of variation in time. Intercountry heterogeneity was shown in components of elapsed time to treatment. Physicians in the prehospital setting enrolled 63.8% of patients. The presence of a physician was associated with greater adherence to protocol mandated treatments and procedures but with delay in time to treatment (120 v 108 minutes, p < 0.001). CONCLUSION: Country of enrollment accounted for the largest proportion of variation in time to treatment and intercountry heterogeneity modulated components of delay. The effectiveness and safety of prehospital fibrinolysis was not influenced by the presence of a physician. These data, acquired in diverse health care environments, provide new understanding into the components of prehospital treatment delay and the opportunities to further reduce time to fibrinolysis for patients with ST elevation myocardial infarction.
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Servicios Médicos de Urgencia/organización & administración , Fibrinolíticos/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Médicos/provisión & distribución , Factores de Edad , Presión Sanguínea/fisiología , Diagnóstico Diferencial , Quimioterapia Combinada , Servicios Médicos de Urgencia/normas , Enoxaparina/administración & dosificación , Europa (Continente) , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , América del Norte , Análisis de Regresión , Tasa de Supervivencia , Tenecteplasa , Terapia Trombolítica/métodos , Terapia Trombolítica/mortalidad , Factores de Tiempo , Activador de Tejido Plasminógeno/administración & dosificaciónRESUMEN
BACKGROUND: A cardinal feature of heart failure (HF) is the reduced peak aerobic power (VO(2peak)) secondary to alterations in cardiovascular and musculoskeletal function. Methods and results During the last decade, a number of randomized trials have examined the role that exercise training plays in attenuating the HF-mediated decline in VO(2peak) and muscle strength. The major finding of these investigations was that aerobic or strength training was an effective intervention to increase VO(2peak), muscular strength, distance walked in 6 minutes, and quality of life without negatively altering left ventricular systolic function. Despite these benefits, a limitation of these investigations was the primary focus on males <60 years with impaired left ventricular systolic function. Thus the role that exercise training may play in attenuating the HF-mediated decline in VO(2peak) in women > or =65 years of age remains unknown. CONCLUSION: Older women with HF have a VO(2peak) that is below the minimal threshold level required for independent living. Moreover, older women with HF have greater disability then men and are less likely to be referred to an exercise rehabilitation program. Accordingly, future exercise intervention trials are required to examine the role that exercise training may play in attenuating the HF-mediated decline in cardiorespiratory and musculoskeletal fitness and disability in older women with HF.
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Terapia por Ejercicio , Insuficiencia Cardíaca/rehabilitación , Consumo de Oxígeno , Factores de Edad , Anciano , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Contracción Muscular/fisiología , Músculo Esquelético/fisiopatologíaRESUMEN
BACKGROUND: Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). OBJECTIVES: To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX-9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. PATIENTS AND METHODS: Patients undergoing elective, native-vessel PCI (n = 175) were randomized 4 : 1 to open-label DX-9065a or heparin in one of four sequential stages. DX-9065a regimens in stages I-III were designed to achieve concentrations of > 100 ng mL-1, > 75 ng mL-1, and > 150 ng mL-1. Stage IV used the stage III regimen but included patients recently given heparin. RESULTS: At 15 min median (minimum) DX-9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL-1 in stages I-IV, respectively. Median whole-blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti-FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL-1, respectively. Stage II enrollment was stopped (n = 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX-9065a dose. CONCLUSIONS: Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double-bolus and infusion DX-9065a dosing. Monitoring of DX-9065a may be possible using whole-blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study.
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Anticoagulantes/administración & dosificación , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Inhibidores del Factor Xa , Naftalenos/administración & dosificación , Propionatos/administración & dosificación , Trombosis/prevención & control , Anciano , Anticoagulantes/sangre , Anticoagulantes/farmacocinética , Pruebas de Coagulación Sanguínea , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Estudios de Factibilidad , Femenino , Heparina/administración & dosificación , Humanos , Relación Normalizada Internacional , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Naftalenos/sangre , Naftalenos/farmacocinética , Proyectos Piloto , Complicaciones Posoperatorias/prevención & control , Propionatos/sangre , Propionatos/farmacocinética , Trombosis/etiologíaRESUMEN
AIM: To study the relationship between outcomes and peak creatine kinase (CK)-MB levels after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). METHODS AND RESULTS: Peak CK-MB ratios (peak CK-MB level/upper limit of normal [ULN]) after PCI were analysed in 6164 patients with NSTE ACS from four randomized trials who underwent in-hospital PCI. We excluded 696 patients with elevated CK or CK-MB levels <24h before PCI; the primary analysis included 2384 of the remaining 5468 patients (43.6%) with CK-MB levels measured <==24h after PCI. The incidence of in-hospital heart failure (0.1%, 0.8%, 3.4%, 4.1%, and 6.1%; P<0.001), arrhythmias (0.8%, 1.9%, 6.9%, 4.1%, and 7.9%; P<0.001), cardiogenic shock (0.1%, 1.3%, 2.0%, 2.3%, and 2.6%; P=0.004), and mortality through 6 months (2.1%, 2.4%, 4.9%, 4.1%, and 5.7%, P=0.005) was increased with peak CK-MB ratios of 0-1, 1-3, 3-5, 5-10, and >10xULN, respectively. The continuous peak CK-MB ratio after PCI significantly predicted adjusted 6-month mortality (risk ratio, 1.06 per unit increase above ULN; 95% confidence interval, 1.01-1.11; P=0.017). CONCLUSIONS: Greater CK-MB elevation after PCI is independently associated with adverse outcomes in NSTE ACS. These results underscore the adverse implications of elevated CK-MB levels after PCI in this high-risk population.
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Enfermedad Coronaria/enzimología , Creatina Quinasa/metabolismo , Isoenzimas/metabolismo , Enfermedad Aguda , Anciano , Biomarcadores/sangre , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/terapia , Forma MB de la Creatina-Quinasa , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Selección de Paciente , Resultado del TratamientoRESUMEN
BACKGROUND: Intracranial haemorrhage is an important limitation to pharmacologic reperfusion therapy for acute myocardial infarction. The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrinolytic therapy in this setting. METHODS AND RESULTS: We evaluated the relation between univariate and multivariate predictors of intracranial haemorrhage and the effect of treatment with either reteplase alone (10 U bolus twice, 30 min apart) with standard-dose heparin (5000 U bolus followed by an infusion of 1000 Uh(-1)for patients > or =80 kg and 800 Uh(-1)for those <80 kg) or combination therapy with abciximab (0.25mg/kg bolus and 0.125 microg/kg/min for 12h) and half-dose reteplase (two boluses of 5U 30 min apart) with reduced-dose heparin (60 Ukg(-1)bolus, maximum 5000 U, followed by an infusion of 7 Ukg(-1)h(-1)) in the 16 588 patients randomized in the GUSTO V trial. Overall, the incidence of intracranial haemorrhage was similar in the two groups (0.6% vs 0.6%; OR 1.05, 95% CI 0.71, 1.56). The median (25th-75th) time from drug administration to intracranial haemorrhage was 5.5 (3.4-11) hours with combination therapy and 9.2 (5.9-22) hours with reteplase (P=0.048). Among the multivariable predictors of intracranial haemorrhage, only age showed a significant interaction with treatment effect (age per treatment interaction chi-square 4.60, P=0.032) with a lower risk of combination therapy for younger patients and a higher risk for the elderly. CONCLUSIONS: Although no additional risk of intracranial haemorrhage has been observed with combination therapy in the whole population, a significant age pertreatment interaction exists, with a lower risk with combination therapy in younger patients, and a higher risk in the elderly.
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Anticuerpos Monoclonales/efectos adversos , Fibrinolíticos/efectos adversos , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Hemorragias Intracraneales/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Proteínas Recombinantes/efectos adversos , Activador de Tejido Plasminógeno/efectos adversos , Abciximab , Quimioterapia Combinada , Femenino , Heparina/efectos adversos , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/efectos adversos , Factores de RiesgoRESUMEN
AIMS: A fibrinolytic agent more effective than streptokinase available for bolus injection with reasonable cost-effectiveness is a desirable goal. Pilot studies with bolus pegulated staphylokinase (PEG-Sak) have revealed excellent Thrombolysis In Myocardial Infarction (TIMI) 3 60-minute flow. METHODS AND RESULTS: We evaluated patients with acute ST-elevation myocardial infarction within 6 hours of chest pain onset to determine a dose of PEG-Sak that had at least equal efficacy to recombinant tissue plasminogen activator (rt-PA) while maintaining an acceptable safety profile. After the initial study of 38 patients, of whom 27 received PEG-Sak, enrollment was temporarily halted because 3 patients receiving PEG-Sak had intracranial hemorrhage: 1 at a dose of 0.15 mg/kg and 2 at a dose of 0.05 mg/kg. Overall, 378 patients were studied across a PEG-Sak dose range from 0.01 mg/kg to 0.015 mg/kg, and 122 patients received accelerated rt-PA. At the lowest dose of PEG-Sak studied, 0.01 mg/kg, there was suggestive evidence of attenuation of efficacy; the point estimate for TIMI 3 flow was 24% (95% CI 9%-38%). At doses of 0.01875 to 0.0375 mg/kg (n = 314), TIMI 3 flow rates were 33% (95% CI 27%-38%), whereas the TIMI 3 flow was 41% (95% CI 20%-61%) at the highest PEG-Sak dose studied, 0.05 mg/kg (n = 23), which was similar to that found with rt-PA, 41% (95% CI 32%-50%). CONCLUSION: The efficacy of PEG-Sak, coupled with its ease of administration, provide further impetus for further study in acute myocardial infarction.
Asunto(s)
Fibrinolíticos/administración & dosificación , Metaloendopeptidasas/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Estreptoquinasa/administración & dosificación , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Adulto , Anciano , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no ParamétricasRESUMEN
BACKGROUND: The combination of a single-bolus fibrinolytic and a low-molecular-weight heparin may facilitate prehospital reperfusion and further improve clinical outcome in patients with ST-elevation myocardial infarction. METHODS AND RESULTS: In the prehospital setting, 1639 patients with ST-elevation myocardial infarction were randomly assigned to treatment with tenecteplase and either (1) intravenous bolus of 30 mg enoxaparin (ENOX) followed by 1 mg/kg subcutaneously BID for a maximum of 7 days or (2) weight-adjusted unfractionated heparin (UFH) for 48 hours. The median treatment delay was 115 minutes after symptom onset (53% within 2 hours). ENOX tended to reduce the composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemia to 14.2% versus 17.4% for UFH (P=0.080), although there was no difference for this composite end point plus in-hospital intracranial hemorrhage or major bleeding (18.3% versus 20.3%, P=0.30). Correspondingly, there were reductions in in-hospital reinfarction (3.5% versus 5.8%, P=0.028) and refractory ischemia (4.4% versus 6.5%, P=0.067) but increases in total stroke (2.9% versus 1.3%, P=0.026) and intracranial hemorrhage (2.20% versus 0.97%, P=0.047). The increase in intracranial hemorrhage was seen in patients >75 years of age. CONCLUSIONS: Prehospital fibrinolysis allows 53% of patients to receive reperfusion treatment within 2 hours after symptom onset. The combination of tenecteplase with ENOX reduces early ischemic events, but lower doses of ENOX need to be tested in elderly patients. At present, therefore, tenecteplase and UFH are recommended as the routine pharmacological reperfusion treatment in the prehospital setting.
Asunto(s)
Servicios Médicos de Urgencia/métodos , Enoxaparina/uso terapéutico , Heparina/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Estudios de Cohortes , Quimioterapia Combinada , Servicios Médicos de Urgencia/estadística & datos numéricos , Enoxaparina/efectos adversos , Femenino , Hemorragia/etiología , Heparina/efectos adversos , Humanos , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Riesgo , Seguridad , Análisis de Supervivencia , Tenecteplasa , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Activador de Tejido Plasminógeno/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Although the prognostic value of admission ST changes in patients with non-ST elevation acute coronary syndrome (ACS) is established, the utility of the discharge ECG is unknown. Accordingly, using the PARAGON-B Troponin substudy, we assessed the prevalence of ST depression on both admission and discharge ECG, the likelihood of developing new Q-waves at discharge and the additional prognostic value of these changes. METHODS AND RESULTS: Nine hundred and eighteen patients were studied; 542 patients (59%) had admission ST downward arrow > or =1mm and 376 patients (41%) did not and their 6-month mortality was 4.4 vs 0.8%, P=0.002, respectively. Of patients with ST downward arrow on admission, 320 (59%) normalized their ST segment at discharge. Of patients without ST downward arrow on admission, 35 (9.3%) developed new ST downward arrow at discharge. Patients with persistent ST downward arrow on discharge had a higher 6-month mortality (6.0 vs 0.9%), (re)MI (16.3 vs 7.4%), and death/(re)MI (20.0 vs 8.3%) than those who never had ST downward arrow (all P< or =0.002). Two hundred and fifty-six patients had Q-waves on admission whereas by discharge 320 had Q-waves. Patients with Q-waves on discharge vs those without had a higher mortality (4.8 vs 1.9%), (re)MI (13.8 vs 8.3%), and death/(re)MI (16.4 vs 9.6%) at 6 months (all P< or =0.021). CONCLUSIONS: This study highlights that the dynamic ECG changes which occur between admission and discharge in non-ST elevation ACS patients allows further risk stratification in determining the likelihood of 6-month death and/or re(MI).
Asunto(s)
Arritmias Cardíacas/fisiopatología , Enfermedad Coronaria/fisiopatología , Tirosina/análogos & derivados , Acetatos/uso terapéutico , Enfermedad Aguda , Anciano , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/cirugía , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/cirugía , Supervivencia sin Enfermedad , Electrocardiografía , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Análisis de Supervivencia , Troponina T/análisis , Tirosina/uso terapéuticoRESUMEN
AIMS: We evaluated timing of adverse cardiac events after thrombolysis to guide length of stay after ST-segment elevation myocardial infarction. METHODS AND RESULTS: Kaplan-Meier survival curves described timing of major postinfarction complications in 41021 fibrinolytic-treated patients in GUSTO-I. Using model-fitting, these data were best explained by a mixed-exponential survival model: an acute curve describing most adverse events and a chronic curve describing a lower background rate. We replicated this strategy in 15059 fibrinolytic-treated patients in GUSTO-III. From the relation between time and events described by the model's acute curve in GUSTO-III, we proposed times for hospital discharge. The acute curve explained 97% of deaths and 68%-96% of various event composites. Of complications within 10 days, 90% of deaths and 70% of acute curve death, stroke, shock, heart failure, or reinfarction occurred by 24 h. By 2.7 days, 95% of deaths, stroke, shock, heart failure, or reinfarction occurred. Most major ventricular arrhythmias occurred within 24 h, after which the hazard curve was flat. CONCLUSIONS: Mixed-exponential survival modelling describes timing of post-infarction complications and supports discharge 4 days after uncomplicated infarction. Such time-based risk assessment could guide decision-making in other settings in which randomized studies are impractical.
Asunto(s)
Toma de Decisiones , Infarto del Miocardio/terapia , Alta del Paciente , Terapia Trombolítica/métodos , Humanos , Tiempo de Internación , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Tasa de Supervivencia , Terapia Trombolítica/mortalidad , Factores de TiempoRESUMEN
AIMS: To evaluate the differential effects of eptifibatide therapy on unstable angina vs non-ST elevation myocardial infarction at enrollment, since the separate impact on these two major diagnostic subsets of acute coronary syndrome patients has not been fully investigated. METHODS AND RESULTS: We examined the 9461 patients in the PURSUIT trial (conducted between 1995 and 1997) to compare the effects of eptifibatide on unstable angina and myocardial infarction. The study showed greater and more consistent effects of eptifibatide therapy on unstable angina than non-ST elevation myocardial infarction in reducing 30-day death/(re)infarction (from the unadjusted rate of 13.0% to 11.2%, P=0.059 for unstable angina; and 18.9% to 17.9%, P=0.387 for myocardial infarction), especially among patients who underwent early percutaneous coronary intervention (odds ratios=0.49 and 0.86, 95% confidence intervals=0.30-0.80 and 0.53-1.42, respectively, for unstable angina and myocardial infarction). The only subgroup for whom the benefit of eptifibatide was not evident was female myocardial infarction patients who did not undergo early percutaneous coronary intervention. CONCLUSIONS: These data suggest that eptifibatide benefited unstable angina patients more than myocardial infarction patients, especially among those who underwent early percutaneous coronary intervention, and support its use as concomitant therapy with early percutaneous coronary intervention especially in female myocardial infarction patients.
Asunto(s)
Angina Inestable/diagnóstico , Angina Inestable/tratamiento farmacológico , Electrocardiografía , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/tratamiento farmacológico , Péptidos/administración & dosificación , Adulto , Factores de Edad , Anciano , Angina Inestable/mortalidad , Eptifibatida , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Probabilidad , Pronóstico , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Factores Sexuales , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Angina Inestable/tratamiento farmacológico , Angioplastia Coronaria con Balón , Heparina/uso terapéutico , Terapia con Hirudina , Hirudinas/análogos & derivados , Isquemia Miocárdica/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Anciano , Angina Inestable/terapia , Cateterismo Cardíaco , Femenino , Heparina/efectos adversos , Hirudinas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/terapia , Proteínas Recombinantes/efectos adversos , Prevención Secundaria , SíndromeRESUMEN
BACKGROUND: Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. METHODS AND RESULTS: In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4.66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5.94% in the rt-PA group (P=0.0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4.25% vs 5.49%, P=0.0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0.93% of patients in the TNK-tPA and 0.94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67 kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1.14% vs 8/265, 3.02%). CONCLUSIONS: The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.