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OBJECTIVE: To determine whether the guidelines for the management of acute coronary syndrome (ACS) are being applied in daily clinical practice, and in what ways the management differs between the Netherlands and other member countries of the European Society of Cardiology (ESC). DESIGN: Prospective, observational study. METHOD: Patients with a confirmed diagnosis of ACS who were enrolled in 6 Dutch hospitals and in 97 hospitals in 24 other ESC member countries in the period from 4 September 2000 to 15 May 2001 were included. Data were collected on the acute treatment and secondary prevention in patients with ST-elevation and on the pharmacotherapy, risk stratification and secondary prevention in patients without ST-elevation. The findings were compared with the recommendations and guidelines of the ESC. RESULTS: A total of 223 patients with ST-elevation and 198 patients without ST-elevation were enrolled in the Netherlands, plus 4208 and 5169 patients, respectively, in the other European countries. The median age was 64-67 years and the percentage of males was 64-73. Of the patients with ST-elevation who arrived in the hospital within 12 hours after the onset of symptoms, 35% received neither thrombolysis nor primary percutaneus coronary intervention. In both the Netherlands and the rest of Europe, half of the ST-elevation patients received thrombolysis later than 40 minutes and primary percutaneous coronary intervention later than 90 minutes after arrival in the hospital. Risk stratification using troponin measurements was applied more often in the Netherlands. Of the high-risk patients without ST-elevation, over 50% in both the Netherlands and the rest of Europe underwent coronary angiography. Almost 70% and 80% of low-risk, non-ST-elevation patients underwent an exercise tolerance test or coronary angiography. In the Netherlands, clopidogrel, glycoprotein IIb/IIIa antagonists and statins were prescribed more often and ACE inhibitors less often. CONCLUSION: Guidelines for the management of ACS were followed to a moderate extent in both the Netherlands and the rest of Europe. The management differed in a number of ways between the Netherlands and the other countries.
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Enfermedad Coronaria/terapia , Electrocardiografía , Guías de Práctica Clínica como Asunto , Enfermedad Aguda , Anciano , Angiografía Coronaria , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/cirugía , Europa (Continente) , Femenino , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Estudios Prospectivos , Factores de Riesgo , Síndrome , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the extent to which Dutch patients with a history of cardiovascular disease and high cholesterol levels, treated in specialised care, are achieving low-cholesterol targets as defined by national guidelines. DESIGN: Hospital-based cohort study. SETTING: Practices of 41 hospital-based cardiologists and internists in the Netherlands. SUBJECTS: 7377 patients. RESULTS: Forty-one percent of the patients with an indication for secondary cardiovascular prevention by lipid-lowering drug treatment were receiving medication and were achieving cholesterol targets, 42% were receiving lipid-lowering medication but had cholesterol levels above target, 11% were not receiving treatment, and 5% had no recent lipid measurements. CONCLUSION: Compared with previous studies, the SOLID study shows that a relatively large percentage of the Dutch patients under specialised care with a history of cardiovascular disease and an indication for cholesterol-reducing therapy are currently being treated. A considerable proportion of the patients, however, are still not receiving optimal treatment and more than 10% are not being treated at all.
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Guidelines for the management of patients with cardiovascular disease are designed to assist cardiologists and other physicians in their practice. Surveys are conducted to assess whether guidelines are followed in practice. The results of surveys on acute coronary syndromes, coronary revascularisation, secondary prevention, valvular heart disease and heart failure are presented. Comparing surveys conducted between 1995 and 2002, a gradual improvement in use of secondary preventive therapy is observed. Nevertheless, important deviations from established guidelines are noted, with a significant variation among different hospitals in the Netherlands and in other European countries. Measures for further improvement of clinical practice include more rapid treatment of patients with evolving myocardial infarction, more frequent use of clopidogrel and glycoprotein IIb/IIIa receptor blockers in patients with acute coronary syndromes, more frequent use of ß-blockers in patients with heart failure and more intense measures to encourage patients to stop smoking. Targets for the proportion of patients who might receive specific therapies are presented.
RESUMEN
Results of surveys and clinical trials have indicated that prognosis of female patients with acute myocardial infarction is worse than prognosis of male patients. Female patients are on average older than male patients, have a longer patient delay, present more often with equivocal ECG abnormalities, and have more often contraindications to thrombolytic therapy. Thrombolytic therapy is given less often to female patients with acute myocardial infarction than to male patients of the same age. This is only partly due to the absence of an indication for thrombolytic therapy or the presence of a contraindication. If thrombolytic therapy is given to female patients with acute myocardial infarction, this results in the same patency rate as in male patients. In the meta-analysis of the Fibrinolytic Therapy Trialists' Collaboration Group that included all randomised clinical trials that compared thrombolytic therapy with a placebo or control group, the absolute benefit of thrombolytic therapy with regard to 35-day mortality was 2.2% in female patients, higher than the observed absolute difference of 1.9% in male patients. In several studies age, gender, and body weight were identified as independent risk factors for the occurrence of stroke and bleeding complications after administration of thrombolytic therapy. Results of the ASSENT-2 study indicated that total stroke rate and 30-day mortality was lower in female patients over 75 years of age treated with tenecteplase than in those treated with alteplase, albeit that the difference was statistically not significant. With the data presently available it can be stated that female patients and patients over 75 years of age will probably benefit more from a thrombolytic agent that is given according to a weight-adjusted dose regimen, e.g., tenecteplase.
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Infarto del Miocardio/tratamiento farmacológico , Terapia Trombolítica , Factores de Edad , Contraindicaciones , Femenino , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Pronóstico , Factores Sexuales , Terapia Trombolítica/efectos adversosRESUMEN
ARGAMI was designed to assess safety and efficacy of argatroban compared with heparin as adjunctive treatment to alteplase in the treatment of patients with acute myocardial infarction. ARGAMI consisted of an open-dose finding study (35 patients) followed by a placebo-controlled study with double dummy technique and 2:1 (argatroban:heparin) randomization. An argatroban dosage of 100 microg/kg bolus plus 3 microg/kg/min infusion for 72 hours was selected for the randomized study in which 82 patients were allocated to argatroban and 45 to heparin (5000 U intravenous bolus, 1000 U/h infusion). Patency of the infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) after 90 minutes was obtained in 62 patients (76%) allocated to argatroban versus 37 patients (82%) allocated to heparin (p=ns). Angiograms after 24 hours and 5 to 10 days showed low reocclusion rates in both groups. Bleeding complications were observed in 16 patients allocated to argatroban (19.5%) and in 9 patients allocated to heparin (20.0%). One patient allocated to heparin suffered from hemorrhage stroke. Argatroban, given as adjunctive treatment to alteplase, is tolerated well in patients with acute myocardial infarction. Safety and efficacy of the combination alteplase and argatroban (with this dose regimen) are similar to those of alteplase and heparin.
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Infarto del Miocardio/tratamiento farmacológico , Ácidos Pipecólicos/farmacocinética , Activador de Tejido Plasminógeno/farmacocinética , Anciano , Angiografía , Anticoagulantes/efectos adversos , Anticoagulantes/sangre , Anticoagulantes/farmacocinética , Arginina/análogos & derivados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Femenino , Hemorragia/inducido químicamente , Heparina/administración & dosificación , Heparina/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Tiempo de Tromboplastina Parcial , Ácidos Pipecólicos/efectos adversos , Ácidos Pipecólicos/sangre , Activadores Plasminogénicos/administración & dosificación , Activadores Plasminogénicos/efectos adversos , Activadores Plasminogénicos/farmacocinética , Sulfonamidas , Tasa de Supervivencia , Factores de Tiempo , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversosRESUMEN
OBJECTIVE: To investigate the value of non-invasive reperfusion indices in acute myocardial infarction, avoiding the possible need for acute coronary angiography and subsequent angioplasty. DESIGN: In a prospective angiographic study, seven potential ECG or clinical markers of reperfusion were analysed in 230 patients with acute myocardial infarction. In all patients two 12 lead ECGs were used: the ECG on admission and the ECG immediately before coronary angiography. Non-invasive markers of reperfusion determined just before coronary angiography were prospectively correlated to thrombolysis in myocardial infarction (TIMI) flow. Data analysis correlated these non-invasive indices with coronary flow (analysis A: TIMI 2-3 v TIMI 0-1 flow; analysis B: TIMI 3 v TIMI 0-2 flow). RESULTS: A sudden decrease in chest pain was the most common sign of reperfusion (36%), followed by reduction in ST segment elevation by >/= 50% (30%), and the development of a terminal negative T wave (20%) in the lead with the highest ST segment elevation. Reduction in ST segment elevation by > or = 50% and the appearance of an accelerated idioventricular rhythm (AIVR) had the highest positive predictive value for reperfusion. For analyses A and B, the positive predictive values were 85% and 66% for resolution of ST segment elevation, and 94% and 59% for AIVR, respectively. The presence of three or more non-invasive markers of reperfusion predicted TIMI 3 flow accurately in 80% of cases. CONCLUSIONS: The prospective use of non-invasive indices of reperfusion is simple, practical, and can be of value in assessing coronary patency in patients admitted with acute myocardial infarction. Using these indices, discrimination between TIMI 0-1 and TIMI 2-3 flow can be made with good accuracy. However, TIMI 3 flow cannot be determined reliably. The use of such non-invasive indices depends on the goal of reperfusion.
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Infarto del Miocardio/terapia , Reperfusión Miocárdica , Angiografía Coronaria/métodos , Electrocardiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice. DESIGN: Randomised controlled trial. PARTICIPANTS: 729 patients aged >/=60 years with atrial fibrillation, recruited in general practice, who had no established indication for coumarin. Mean age was 75 years and mean follow up 2. 7 years. SETTING: Primary care in the Netherlands. INTERVENTIONS: Patients eligible for standard intensity coumarin (international normalised ratio 2.5-3.5) were randomly assigned to standard anticoagulation, very low intensity coumarin (international normalised ratio 1.1-1.6), or aspirin (150 mg/day) (stratum 1). Patients ineligible for standard anticoagulation were randomly assigned to low anticoagulation or aspirin (stratum 2). MAIN OUTCOME MEASURES: Stroke, systemic embolism, major haemorrhage, and vascular death. RESULTS: 108 primary events occurred (annual event rate 5.5%), including 13 major haemorrhages (0.7% a year). The hazard ratio was 0.91 (0.61 to 1.36) for low anticoagulation versus aspirin and 0.78 (0.34 to 1.81) for standard anticoagulation versus aspirin. Non-vascular death was less common in the low anticoagulation group than in the aspirin group (0.41, 0.20 to 0.82). There was no significant difference between the treatment groups in bleeding incidence. High systolic and low diastolic blood pressure and age were independent prognostic factors. CONCLUSION: In a general practice population (without established indications for coumarin) neither low nor standard intensity anticoagulation is better than aspirin in preventing primary outcome events. Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice.
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Anticoagulantes/administración & dosificación , Aspirina/administración & dosificación , Fibrilación Atrial/prevención & control , Cumarinas/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Tromboembolia/prevención & control , Anciano , Anticoagulantes/efectos adversos , Aspirina/efectos adversos , Cumarinas/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the safety and feasibility of acute transport followed by rescue percutaneous transluminal coronary angioplasty (PTCA) or primary PTCA in patients with acute myocardial infarction initially admitted to a hospital without PTCA facilities. DESIGN: In a multicentre randomised open trial, three regimens of treatment of acute large myocardial infarction were compared for patients admitted to hospitals without angioplasty facilities: thrombolytic treatment with alteplase (75 patients), alteplase followed by transfer to the PTCA centre and (if indicated) rescue PTCA (74 patients), or transfer for primary PTCA (75 patients). RESULTS: Between 1995 and 1997 224 patients were included. Baseline characteristics were distributed evenly. Transport to the PTCA centre was without severe complications in all patients. Mean (SD) delay from onset of symptoms to randomisation was 130 (75) minutes and from randomisation to angiography 90 (25) minutes. Death or recurrent infarction within 42 days occurred in 12 patients in the thrombolysis group, in 10 patients in the rescue PTCA group, and in six patients in the primary PTCA group. These differences were not significant. CONCLUSIONS: Acute transfer for rescue PTCA or primary PTCA in patients with extensive myocardial infarction is feasible and safe. Efficacy of rescue PTCA or primary PTCA in this setting will have to be tested in larger series before this approach can be implemented as "routine treatment" for patients with extensive myocardial infarction.
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Angioplastia Coronaria con Balón/estadística & datos numéricos , Tratamiento de Urgencia , Infarto del Miocardio/terapia , Transferencia de Pacientes , Terapia Trombolítica/estadística & datos numéricos , Estudios de Factibilidad , Fibrinolíticos/uso terapéutico , Humanos , Infarto del Miocardio/tratamiento farmacológico , Proyectos Piloto , Estudios Prospectivos , Factores de Tiempo , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
BACKGROUND: Short-term safety and efficacy of thrombolysis with saruplase in acute myocardial infarction have been shown in several trials. To assess long-term outcome of patients treated with saruplase or streptokinase for myocardial infarction, a 5-year follow-up of patients included in the Pro-Urokinase in Myocardial Infarction Trial was performed. METHODS AND RESULTS: Follow-up data are available from 8 centers on 255 (92.4%) of 276 included patients. The 5-year mortality rate was comparable with 20.8% of patients in the saruplase group and 16.9% in the streptokinase group (odds ratio 1.29, 95% confidence interval 0.69 to 2.42). In both groups, a considerable number of fatal cardiovascular events occurred more than 1 year after study inclusion. Rates of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting were comparable in both groups. Reinfarction within 5 years occurred in 19.0% of patients in the saruplase group and tended to be less frequent at 10.8% after streptokinase treatment (odds ratio 1.94, 95% confidence interval 0.98 to 3.84). In both groups, the majority of reinfarctions took place more than 3 months after study inclusion. The 5-year stroke rate was 3.6% and 7.2% in the saruplase and streptokinase groups, respectively (odds ratio 0.49, 95% confidence interval 0.16 to 1.47). Subjective symptoms of heart failure and angina pectoris were comparable in both groups. CONCLUSIONS: Our data are consistent with a similar long-term outcome for patients treated with saruplase or streptokinase. Despite the low-risk profile of the patient cohort, there were considerable adverse event rates over a 5-year period.
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Fibrinolíticos/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Estreptoquinasa/uso terapéutico , Terapia Trombolítica , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéutico , Anciano , Angioplastia Coronaria con Balón/estadística & datos numéricos , Trastornos Cerebrovasculares/epidemiología , Estudios de Cohortes , Puente de Arteria Coronaria/estadística & datos numéricos , Femenino , Fibrinolíticos/efectos adversos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Recurrencia , Estreptoquinasa/efectos adversos , Análisis de Supervivencia , Activador de Plasminógeno de Tipo Uroquinasa/efectos adversosRESUMEN
Patients with nonrheumatic atrial fibrillation (NRAF) have a higher risk of thromboembolism than patients in sinus rhythm. Several trials have been conducted to establish the best preventive regimen in patients with NRAF, but not in the primary-care setting. The Primary Prevention of Arterial Thromboembolism in Nonrheumatic Atrial Fibrillation (PATAF) study, a primary-care-based trial, was set up to compare the preventive efficacy of low-intensity anticoagulation (AC), target range International Normalized Ratio (INR) 1.1 < INR < 1.6 and regular-intensity AC (2.5 < INR < 3.5) therapies with that of aspirin 150 mg/d for the occurrence of thromboembolism in NRAF patients. Patients eligible for regular-intensity AC were randomly assigned to aspirin at 150 mg/d, low-intensity AC, or regular AC in group I. In cases of noneligibility for regular AC, the trial randomized patients between aspirin and low-intensity AC (assigned to group II). Primary outcome events were stroke (including intracranial hemorrhage), systemic embolism, major hemorrhage, or vascular death. Analysis of the data was based on Cox regression to compute the hazard ratio (HR) with a 95% confidence interval, using the likelihood ratio test. The trial randomized 729 patients. Patient enrollment and follow-up has been stopped, and the final analysis is now complete. We shall publish the main results as soon as possible.
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Anticoagulantes/administración & dosificación , Aspirina/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Tromboembolia/prevención & control , Anciano , Anticoagulantes/efectos adversos , Aspirina/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Países Bajos , Atención Primaria de Salud , Resultado del TratamientoRESUMEN
Saruplase (unglycosylated human-type high molecular weight single-chain urokinase-type plasminogen activator) was given to 1698 patients in the open-label Practical Applicability of Saruplase Study (PASS), which assessed the safety and efficacy of saruplase in the treatment of acute myocardial infarction. Thirty-seven hospitals in Europe participated in the study. All patients received 20 mg saruplase as a bolus followed by an infusion of 60 mg saruplase over 1 hour. Prior to the infusion of saruplase, 62% of the patients received a bolus of 5000 U of heparin, and after saruplase a 24-hour intravenous infusion of heparin was given to 95% of patients. The mean age of the patients was 59 years and 80.1% were male. The median delay from the onset of chest pain to the start of saruplase infusion was 145 minutes. Acute angiography was performed in 8 of the participating 37 centers in 350 patients (20.6%), on average 85 minutes (median) after the start of the saruplase infusion. TIMI 3 flow was obtained in 186 patients (53.1%) and TIMI 2 flow in 61 patients (17.4%). Patency rates were similar for patients with anterior and inferior infarction. ECG signs suggestive of reperfusion were seen in 63% of the patients. In-hospital mortality was low (92 patients; 5.4%), and nonfatal recurrent myocardial infarction was seen in 60 patients (3.5%). Severe bleeding complications occurred in 92 patients (5.4%), 21 of whom (1.2%) needed a blood transfusion. An intracerebral hemorrhage was observed in eight patients (0.5%), and seven patients (0.4%) suffered from a thromboembolic stroke. At discharge 85.9% of the patients were in NYHA functional class I. One-year mortality was low (142 patients; 8. 4%). Mortality was high in patients with TIMI 0 or 1 flow at the acute angiography who did not undergo rescue PTCA (9/39; 23.1%), lower in patients with TIMI 0 or 1 flow followed by successful rescue PTCA (7/64; 10.9%), and low in patients with TIMI 2 flow (1/61; 1.6%) or with TIMI 3 flow (2/186; 1.1%). Patency rates and (bleeding) complications did not differ between patients with a body weight greater than or less than 70 kilograms. No antibodies against saruplase were detected in samples from 455 patients. In conclusion, it can be stated that saruplase, given in combination with aspirin and intravenous heparin, can be given safely and effectively to patients with acute myocardial infarction.
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Fibrinolíticos/administración & dosificación , Heparina/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Anciano , Quimioterapia Combinada , Femenino , Fibrinolíticos/efectos adversos , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Resultado del Tratamiento , Activador de Plasminógeno de Tipo Uroquinasa/efectos adversosRESUMEN
AIMS: To investigate whether the benefit of thrombolytic therapy was sustained beyond the first decade. We report the 10-14 year outcome of 533 patients who were randomized to treatment with intracoronary streptokinase or to conventional therapy during the years 1980-1985. METHODS AND RESULTS: Details of survival and cardiac events were obtained from the civil registry, from medical records or from the patient's physician. At follow-up, 158 patients (59%) of the 269 patients allocated to thrombolytic treatment and only 129 patients (49%) of the 264 conventionally treated patients were alive. The cumulative 1-, 5- and 10-year survival rates were 91%, 81% and 69% in patients treated with streptokinase and 84%, 71% and 59% in the control group, respectively (P=0.02). Reinfarction during 10-years of follow-up was more frequent after thrombolytic therapy, particularly during the first year. Coronary bypass surgery and coronary angioplasty were more frequently performed after thrombolytic therapy. At 10 years approximately 30% of the patients were free from subsequent cardiac events. Independent determinants of mortality were elderly age, indicators of impaired residual left ventricular function, multivessel disease and an inability to perform an exercise test at the time of hospital discharge. CONCLUSION: Improved survival after thrombolytic therapy is maintained beyond the first decade. Age, left ventricular function, multivessel disease and an inability to perform an exercise test were independent predictors for long-term mortality, as they are predictors for early mortality.
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Fibrinolíticos/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Estreptoquinasa/uso terapéutico , Terapia Trombolítica , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Infarto del Miocardio/cirugía , Revascularización Miocárdica , Países Bajos/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: If no in-house facilities for percutaneous transluminal coronary angioplasty (PTCA) are present, thrombolytic therapy is the treatment of choice for acute myocardial infarction (AMI). A few studies have shown benefit from rescue PTCA in patients directly admitted to centers with PTCA facilities. The obvious question arises whether patients with AMI initially admitted to a community hospital can benefit from early transfer for intentional rescue PTCA. METHODS AND RESULTS: One hundred sixty-five patients were transferred early for intentional rescue PTCA from a community hospital at a distance of 20 miles. On arrival at the angioplasty center, bedside markers were used to determine reperfusion. In case of obvious reperfusion, no invasive procedure was done; otherwise, coronary angiography and rescue PTCA, if necessary, was performed. During transfer, 1 (1%) patient died and 15 (9%) patients had arrhythmic or hemodynamic problems. Median time delay between onset of chest pain and arrival at the community hospital and the PTCA center was 61 minutes (range 0 to 413) and 150 minutes (range 28 to 472), respectively. In 66 (40%) patients, reperfusion was diagnosed by noninvasive reperfusion criteria on arrival at the PTCA center (group 1). Ninety-eight (59%) patients without evident noninvasive criteria of reperfusion underwent angiography 187 median minutes after the onset of chest pain. Forty-one (25%) patients had Thrombolysis In Myocardial Infarction grade 3 flow, and no further intervention was performed (group 2). In the remaining 57 (35%) patients, rescue PTCA was performed, which was successful in 96% (group 3). In-hospital mortality rate was lowest in group 1 compared with the other 2 groups (0% vs 7% vs 11%; P <.05). Reinfarction was highest in group 1 compared with the other groups (17% vs 5% vs 2%; P <.01). No significant differences were found in coronary artery bypass grafting, stroke, or bleeding complications. The 1-year follow-up data showed low revascularization rates; 2 (1%) patients died after discharge from the hospital. CONCLUSIONS: Early transfer of patients with large AMI for intentional rescue PTCA can be done with acceptable safety and is feasible within therapeutically acceptable time limits and results in additional early reperfusion in 33% of patients. A large, randomized, multicenter trial is needed to compare efficacy of intravenous thrombolytic treatment in a community hospital versus early referral for either rescue or primary PTCA.
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Angioplastia Coronaria con Balón , Hospitales Comunitarios , Infarto del Miocardio/terapia , Derivación y Consulta , Terapia Trombolítica , Angiografía Coronaria , Urgencias Médicas , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Seguridad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. METHODS AND RESULTS: InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P<0. 001). Similar results were observed at 90 minutes (26.1% to 57.1%, P<0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. CONCLUSIONS: Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.
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Angiografía Coronaria , Infarto del Miocardio/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversosRESUMEN
To study the safety and efficacy of the thrombolytic agent saruplase as a bolus, the angiographic and clinical outcomes of three bolus regimens were investigated in a pilot study conducted in 192 patients with an acute myocardial infarction and were compared with the standard regimen. Fifty-two patients received a double bolus of 40 mg and 40 mg after 30 minutes, 51 patients a bolus of 80 mg, and 36 patients a bolus of 60 mg. Fifty-three patients received the standard regimen (a bolus of 20 mg and 60 mg IV infusion over 1 hour). At 60 minutes TIMI 2 and 3 flow were, respectively, 9.6% and 61.5% with the 40/40-mg bolus, 15.7% and 51.0% with the 80-mg bolus, 16.7% and 30.6% with the 60-mg bolus, and 7.5% and 54.7% with the standard 20/60-mg infusion. At 90 minutes TIMI 2 and 3 flow improved to 9.6% and 73.1%, 15.7% and 56.9%, 13.9% and 36.1%, and 5.7% and 71.7%, respectively. The primary endpoint, persistent patency (TIMI 2 + 3) at 24-45 hours, was seen in 69.2%, 64.7%, 44.4%, and 67.9% of patients who had no rescue PTCA, respectively. Inclusion in the 60-mg bolus group was prematurely stopped because of their low patency rates. The 40/40-mg bolus group had the highest mortality rate (13.5%), whereas the 60-mg bolus group had no deaths. Other adverse event rates were similar in the four groups. This clinical outcome is highly influenced by rescue PTCA of patients with insufficient TIMI flow. This pilot study indicates that in patients with an acute myocardial infarction, a double bolus of 40/40 mg resulted in the highest patency but also had the highest complication rate. The 80-mg single bolus is an attractive alternative for further evaluation because of its acceptable patency and event profile, and its easy form of administration.
Asunto(s)
Fibrinolíticos/farmacología , Infarto del Miocardio/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Activador de Plasminógeno de Tipo Uroquinasa/farmacología , Ensayos Clínicos como Asunto , Fibrinolíticos/uso terapéutico , Humanos , Infarto del Miocardio/etiología , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Terapia Trombolítica/métodos , Trombosis/complicaciones , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéuticoRESUMEN
BACKGROUND: During the past decade, various new treatments have become available for patients with acute myocardial infarction. The effects of these treatment modalities have been studied extensively in selected patient groups. These studies indicate that early diagnosis, risk stratification and prompt initiation of treatment are of crucial importance for optimal benefit. However, it is not known whether prognosis changed in all patients admitted with an acute myocardial infarction. Also, the characteristics of the infarct population may have changed over time because of new medication regimens, invasive interventions and awareness of the importance of risk factors. METHODS: We studied all patients admitted with acute myocardial infarction in 1982, 1988 and 1994. Information on baseline characteristics, clinical variables and all interventions was collected. FINDINGS: In those 3 years 223, 227 and 235 patients were admitted because of an acute myocardial infarction. Patients admitted in 1994 were older, more often female and less often had a previous cardiac history. More patients admitted in that year had previous balloon angioplasty and coronary bypass grafting. Smoking habits decreased during the past decade. In-hospital mortality was 38 (17%) in 1982, 23 (10%) in 1988 and 22 (9%) in 1994 (P < 0.05). Variables related to high risk for in-hospital death in 1982 were higher age, low systolic blood pressure, atrial fibrillation, absence of accelerated idioventricular rhythm, sustained ventricular tachycardia and signs of left ventricular dysfunction; in 1988 the occurrence of non-sustained ventricular tachycardia, Killip class more than I, the absence of thrombolytic therapy, percutaneous transluminal coronary angioplasty or coronary artery bypass grafting were independently related to in-hospital death. In 1994, high risk variables for in-hospital death were dyspnoea on admission, sustained ventricular tachycardia, female gender, higher creatinine on admission, and a previous cardiac history. INTERPRETATION: In-hospital mortality for unselected patients admitted with an acute myocardial infarction decreased between 1982 and 1988 and remained the same between 1988 and 1994, in spite of further ageing of the population. In the study period there has been a change in baseline characteristics and high risk variables for in-hospital death after myocardial infarction.
Asunto(s)
Mortalidad Hospitalaria , Infarto del Miocardio/mortalidad , Anciano , Causas de Muerte , Femenino , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Análisis Multivariante , Infarto del Miocardio/terapia , Países Bajos/epidemiología , Análisis de Regresión , Factores de RiesgoRESUMEN
Four hundred seventy-three patients with acute myocardial infarction (AMI) were treated with either saruplase (80 mg/hour, n = 236) or alteplase (100 mg every 3 hours, n = 237). Comedication included heparin and acetylsalicylic acid. Angiography was performed at 45 and 60 minutes after the start of thrombolytic therapy. When flow was insufficient, angiography was repeated at 90 minutes. Coronary angioplasty was then performed if Thrombolysis In Myocardial Infarction (TIMI) trial 0 to 1 flow was seen. Control angiography was at 24 to 40 hours. Baseline characteristics were similar. Angiography showed comparable and remarkably high early patency rates (TIMI 2 or 3 flow) in both treatment groups: at 45 minutes, 74.6% versus 68.9% (p = 0.22); and at 60 minutes 79.9% versus 75.3% (p = 0.26). Patency rates at 90 minutes before additional interventions were also comparable (79.9% and 81.4%). Angiographic reocclusion rates were not significantly different: 1.2% versus 2.4% (p = 0.68). After rescue angioplasty, angiographic reocclusion rates of 22.0% and 15.0% were observed. Safety data were similar for both groups. Thus, (1) early patency rates were high for saruplase and alteplase treatment, (2) reocclusion rates for both drugs were remarkably low, and (3) complication rates were similar. Thus, saruplase seems to be as safe and effective as alteplase.
Asunto(s)
Fibrinolíticos/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Activadores Plasminogénicos/administración & dosificación , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Anciano , Método Doble Ciego , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Proteínas Recombinantes/administración & dosificación , Recurrencia , Terapia Trombolítica/estadística & datos numéricos , Resultado del TratamientoRESUMEN
Evidence is increasing that a patent culprit artery improves the prognosis of patients with acute myocardial infarction (AMI). Primary percutaneous transluminal coronary angioplasty (PTCA) has shown to be more effective than thrombolytic therapy alone. How effective is rescue PTCA after failed thrombolytic treatment? In a retrospective analysis, 176 consecutive patients with AMI and TIMI 0 or 1 perfusion grade were included. Patients had either rescue PTCA after failed thrombolysis (100 patients) or primary PTCA (76 patients). Angiographic data and in-hospital and 1-year outcome were analyzed. Comparison of baseline data of the two groups showed a higher proportion of long-standing angina and use of nitrates and aspirin in the primary PTCA group. Also, the delay between the onset of pain and PTCA was not significantly different, with a mean of 222 minutes for rescue PTCA and 245 minutes for primary PTCA (p = 0.52). The angiographic outcomes in the rescue PTCA group and the primary PTCA group were identical: The intervention was successful (TIMI 3 flow and residual stenosis <50%) in 86.0% and 85.5%, respectively. Complication rates of the procedure were also similar, except for bleeding complications. Blood transfusion was only needed after rescue PTCA in 3.0% versus 0.0% in primary PTCA patients. Clinical outcomes during hospital stay in terms of death rate (4.0% and 6.6%), reinfarction (6.0% and 3.9%), recurrent angina (16.0% and 11.8%), and repeat interventions were comparable, as was the first-year outcome. Failed PTCA was the most important predictor of a poor 1-year outcome; 28.0% died after failed PTCA versus 4.6% after successful PTCA (p < 0.001). In this retrospective analysis of 176 AMI patients, angiographic and clinical outcome, including a 1-year follow-up in patients who had rescue PTCA after failed thrombolysis, were of the same magnitude of patients in whom primary PTCA was performed. These findings suggest that in this subset the outcome of patients with rescue PTCA because of failed thrombolysis is good and is comparable with patients who underwent primary PTCA.