Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension.

OBJECTIVE: To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension (PAH). BACKGROUND: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury. METHODS: Before sitaxsentan withdrawal, this 18-week double-blind, placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily. The primary efficacy endpoint was change from baseline in 6-min walk distance (6MWD) at week 18. Changes in World Health Organization (WHO) functional class and time to clinical worsening (TTCW) were secondary endpoints. The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo. RESULTS: Of 98 randomized patients, 61% were WHO functional class II at baseline. Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg; a strong placebo effect was observed. At week 18, WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo (P = 0.038); 0% versus 12% of patients deteriorated, respectively. TTCW was not significantly different for 100-mg sitaxsentan patients than placebo (P = 0.090). Adverse events (AEs) occurring more frequently with sitaxsentan (50 or 100 mg) included headache, peripheral edema, dizziness, nausea, extremity pain, and fatigue; most AEs were of mild or moderate severity. CONCLUSION: Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline. No patient receiving sitaxsentan 100 mg experienced clinical worsening; sitaxsentan was well tolerated.

[Alteplase in acute coronary syndromes]. / Registro de Alteplasa en Síndromes Coronarios Agudos con elevación del ST (REALSICA).

OBJECTIVE: The registry intends to establish the safety and security of one-hour 100 mg alteplase infusion and 50 mg in 30 minutes to facilitate percutaneous coronary intervention (PCI) in a cardiology hospital with primary angioplasty program (24 hours 365 days a year) with current doses of unfractionated heparin and enoxaparin. METHODS AND RESULTS: REALSICA II is a prospective registry that included 103 patients with final diagnosis of ST elevation myocardial infarction in which Alpert's quality criteria were used. Seventy two patients were under one-hour 100 mg alteplase infusion and thirty one under 30 minutes 50 mg alteplase infusion to facilitate PCI. Patients were young and predominantly males. In both groups > 50% had extensive ST elevation myocardial infarction and 68% were Killip & Kimball I. The majority received reperfusion > 3 hours after the onset of symptoms. In-hospital and follow-up treatment were compliant with Mexican Cardiology Society guidelines. ECG reperfusion was observed in 59% and TIMI III flow in 19% of PCI group. Any intracranial hemorrhage was observed. Global cardiovascular mortality was 11%. Patients under PCI had low incidence of recurrent ischemia and reinfarction. CONCLUSION: REALSICA registry showed in non-complicate acute myocardial infarction ST elevation safety and security of one-hour 100 mg alteplase infusion with current recommended unfractionated heparin and enoxaparin doses in ST elevation myocardial infarction. In complicated patients the regimen to facilitate PCI was associated with increased hemorrhagic complications and requires further research.

[Risk marker stratification in coronary acute syndromes]. / Marcadores en la estratificación de los síndromes coronarios agudos.

Acute coronary syndromes have a heterogeneous clinical presentation with a broad spectrum for mortality and adverse events. It is mandatory to identify high risk groups for percutaneous coronary intervention and intensive antithrombotic treatment or common risk for standard treatment. In contemporaneous medicine it is important to get adequate risk stratification because the impact of hospitalary costs, antithrombotic and reperfusion treatment on health systems. The current pathophysiology of atherosclerosis is moving from a disease secondary to cholesterol deposit, to an inflammatory disease. In the stratification process, familiar history, chest pain, ST dynamic abnormalities, left ventricular wall motion abnormalities, all have predictive value. The association of indirect endothelial dysfunction, micro or macronecrosis and ventricular dysfunction markers increase this value. In our experience a close relationship among abnormal fibrinolysis, inflammation and anticoagulation proteins with adverse events has been proved in acute coronary syndromes. Other interesting finding--for it accessibility--in acute myocardial infarction under coronary percutaneous intervention is persistent ST elevation, leukocytes and fibrinogen predictive value. In population allelic polymorphisms -455A and -148T and fibrinogen ( >450 mg/dL) were associated with coronary disease. These polymorphisms improve risk stratification of coronary disease to establish a better secondary prevention and treatment.

[Risk profile and survival in patients with heart failure caused by systolic function. Prospective study with 4-year follow-up]. / Perfil de riesgo y supervivencia en pacientes con insuficiencia cardíaca por disfunción sistólica. Estudio prospectivo con seguimiento a cuatro años.

BACKGROUND: Our current knowledge on the prognosis of systolic left ventricular dysfunction has been obtained through multicentric trials performed at third level health care institutions, which usually include patients based on strict inclusion criteria. OBJECTIVE: To establish in systolic left ventricular dysfunction patients, evaluated at a community hospital, a risk profile for adverse cardiovascular events and to know their survival. METHODS: Prospective study with 4 years follow-up. INCLUSION CRITERIA: a) Symptomatic patients with systolic left ventricular dysfunction, b) any NYHA functional class or etiology, c) ejection fraction < 40%. EXCLUSION CRITERIA: a) Asymptomatic patients, b) acute coronary syndrome in the last 6 weeks, c) ventricular dysfunction secondary to pulmonary arterial hypertension, d) severe systemic illness or neoplasms causing disability < 6 months. STATISTICS: Student's test, Chi-square, Yates and Mantel-Haenszel. Unvariant and multivariant logistic regression analysis. Cox and Kaplan-Meier method. Significance was set at p < 0.05. RESULTS: From January 1997 to January 2001, 110 patients were studied, 61% men and 39% women, their age were 61 +/- 13.1 years. Ischemic etiology in 46% and 54%, 68% in III/IV NYHA class and 32% in I/II NYHA class. Basal left ventricular ejection fraction was 28 +/- 6.9%. Patients were followed for 30.11 +/- 18.7 months, with 26% of global mortality. Through lineal, logistic and multivariate regression analysis, the high clinical risk profile was identified, corresponding > 65 years, female gender, hypertension, diabetes mellitus II, ischemic heart disease, III/IV NYHA class and ventricular tachycardia (p = 0.00001). CONCLUSION: In the "real world" of systolic left ventricular dysfunction, the identified risk profile allows stratify high priority subgroup of patients to be enrolled in a cardiac transplant program.

Registro de Alteplasa en Síndromes Coronarios Agudos con elevación del ST (REALSICA) / Alteplase in acute coronary syndromes

OBJECTIVE: The registry intends to establish the safety and security of one-hour 100 mg alteplase infusion and 50 mg in 30 minutes to facilitate percutaneous coronary intervention (PCI) in a cardiology hospital with primary angioplasty program (24 hours 365 days a year) with current doses of unfractionated heparin and enoxaparin. METHODS AND RESULTS: REALSICA II is a prospective registry that included 103 patients with final diagnosis of ST elevation myocardial infarction in which Alpert's quality criteria were used. Seventy two patients were under one-hour 100 mg alteplase infusion and thirty one under 30 minutes 50 mg alteplase infusion to facilitate PCI. Patients were young and predominantly males. In both groups > 50% had extensive ST elevation myocardial infarction and 68% were Killip & Kimball I. The majority received reperfusion > 3 hours after the onset of symptoms. In-hospital and follow-up treatment were compliant with Mexican Cardiology Society guidelines. ECG reperfusion was observed in 59% and TIMI III flow in 19% of PCI group. Any intracranial hemorrhage was observed. Global cardiovascular mortality was 11%. Patients under PCI had low incidence of recurrent ischemia and reinfarction. CONCLUSION: REALSICA registry showed in non-complicate acute myocardial infarction ST elevation safety and security of one-hour 100 mg alteplase infusion with current recommended unfractionated heparin and enoxaparin doses in ST elevation myocardial infarction. In complicated patients the regimen to facilitate PCI was associated with increased hemorrhagic complications and requires further research.

Marcadores en la estratificación de los síndromes coronarios agudos / Risk marker stratification in coronary acute syndromes

Acute coronary syndromes have a heterogeneous clinical presentation with a broad spectrum for mortality and adverse events. It is mandatory to identify high risk groups for percutaneous coronary intervention and intensive antithrombotic treatment or common risk for standard treatment. In contemporaneous medicine it is important to get adequate risk stratification because the impact of hospitalary costs, antithrombotic and reperfusion treatment on health systems. The current pathophysiology of atherosclerosis is moving from a disease secondary to cholesterol deposit, to an inflammatory disease. In the stratification process, familiar history, chest pain, ST dynamic abnormalities, left ventricular wall motion abnormalities, all have predictive value. The association of indirect endothelial dysfunction, micro or macronecrosis and ventricular dysfunction markers increase this value. In our experience a close relationship among abnormal fibrinolysis, inflammation and anticoagulation proteins with adverse events has been proved in acute coronary syndromes. Other interesting finding--for it accessibility--in acute myocardial infarction under coronary percutaneous intervention is persistent ST elevation, leukocytes and fibrinogen predictive value. In population allelic polymorphisms -455A and -148T and fibrinogen ( >450 mg/dL) were associated with coronary disease. These polymorphisms improve risk stratification of coronary disease to establish a better secondary prevention and treatment.

Perfil de riesgo y supervivencia en pacientes con insuficiencia cardíaca por disfunción sistólica: Estudio prospectivo con seguimiento a cuatro años / Prognosis of systolic left ventricular dysfunction

Antecedentes: Conocemos el pronóstico de la insuficiencia cardíaca por disfunción sistólica a través de estudios multicéntricos realizados en centros de tercer nivel que generalmente incluyen pacientes con estrictos criterios de inclusión. Objetivo: Establecer un perfil de riesgo para eventos cardiovasculares adversos y conocer la supervivencia en enfermos de un hospital comunitario con insuficiencia cardíaca por disfunción sistólica. Métodos: Estudio prospectivo con seguimiento a 4 años. Inclusión: a) manifestaciones clínicas de insuficiencia cardíaca por disfunción sistólica, b) cualquier clase funcional de la New York Heart Association (NYHA), c) disfunción sistólica de cualquier etiología, d) FE del ventrículo izquierdo < 40%. Exclusión: a) paciente asintomático, b) síndrome coronario agudo en las últimas 6 semanas, c) disfunción ventricular secundaria hipertensión arterial pulmonar, d) enfermedad sistémica grave o neoplasia que límite la vida < 6 meses. Estadística: t de Student, chi cuadrada, Yates y Mantel-Haenszel. Análisis de regresión logística univariado y multivariado. Curvas de supervivencia de Cox y Kaplan-Meier. Significancia estadística: p < de 0.05. Resultados: de enero de 1997 a enero del 2001, 110 pacientes fueron incluidos, 61% del sexo masculino y 39% femeninos, con edad de 61 ± 13.1 años. Se consideró etiología isquémica en 46% y no isquémica en 54%, al ingreso la clase funcional fue III/IV en el 68% y I/II en el 32% con una FE de 28 ± 6.9%. La media de seguimiento fue de 30.11 ± 18.71 meses y se observó una mortalidad global del 26%. A través de los modelos de regresión lineal, logística y multivariado se identificó como perfil de alto riesgo para eventos adversos cardiovasculares: edad > 65 años, sexo femenino, hipertensión arterial sistémica, diabetes mellitus, cardiopatía isquémica, clase III-IV de la NYHA y taquicardia ventricular. (p = 0.00001). Conclusión: En el "mundo real" de la insuficiencia cardíaca por disfunción sistólica, el perfil de riesgo identificado por una mayor morbilidad y mortalidad, permite estratificar un subgrupo de pacientes con prioridad alta para integrarse a un programa de trasplante cardíaco.

Background: Our current knowledge on the prognosis of systolic left ventricular dysfunction has been obtained through multicentric trials performed at third level health care institutions, which usually include patients based on strict inclusion criteria. Objective: To establish in systolic left ventricular dysfunction patients, evaluated at a community hospital, a risk profile for adverse cardiovascular events and to know their survival. Methods: Prospective study with 4 years follow-up. Inclusion criteria: a) Symptomatic patients with systolic left ventricular dysfunction, b) any NYHA functional class or etiology, c) ejection fraction < 40%. Exclusion criteria: a) Asymptomatic patients, b) acute coronary syndrome in the last 6 weeks, c) ventricular dysfunction secondary to pulmonary arterial hypertension, d) severe systemic illness or neoplasms causing disability < 6 months. Statistics: Student's t test, Chi-square, Yates and Mantel-Haenszel. Unvariant and multivariant logistic regression analysis. Cox and Kaplan-Meier method. Significance was set at p < 0.05. Results: From January 1997 to January 2001, 110 patients were studied, 61% men and 39% women, their age were 61 ± 13.1 years. Ischemic etiology in 46% and 54%, 68% in III/IV NYHA class and 32% in I/II NYHA class. Basal left ventricular ejection fraction was 28 ± 6.9%. Patients were followed for 30.11 ± 18.7 months, with 26% of global mortality. Through lineal, logistic and multivariate regression analysis, the high clinical risk profile was identified, corresponding > 65 years, female gender, hypertension, diabetes mellitus II, ischemic heart disease, III/IV NYHA class and ventricular tachycardia (p = 0.00001). Conclusion: In the "real world" of systolic left ventricular dysfunction, the identified risk profile allows stratify high priority subgroup of patients to be enrolled in a cardiac transplant program. (Arch Cardiol Mex 2003; 73:197-204).