RESUMEN

OBJECTIVE: Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome. RESEARCH DESIGN AND METHODS: In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg daily or placebo, beginning 4-12 weeks after an acute coronary syndrome. Absence of diabetes at baseline was based on medical history, no use of antihyperglycemic medication, and hemoglobin A1c and serum glucose levels below diagnostic thresholds. Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, new use of antihyperglycemic medication, hemoglobin A1c ≥6.5%, or a combination of at least two measurements of serum glucose ≥7.0 mmol/L (fasting) or ≥11.1 mmol/L (random). RESULTS: At baseline, 10,645 patients (67% of the trial cohort) did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 403 of 5,326 patients (7.6%) assigned to dalcetrapib and in 516 of 5,319 (9.7%) assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68-0.88; P < 0.001), and a need to treat 40 patients for 3 years to prevent 1 incident case of diabetes. Considering only those with prediabetes at baseline, the number needed to treat for 3 years to prevent 1 incident case of diabetes was 25. Dalcetrapib also decreased the number of patients who progressed from normoglycemia to prediabetes and increased the number who regressed from diabetes to no diabetes. CONCLUSIONS: In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.

Asunto(s)

Amidas/uso terapéutico , Enfermedad Coronaria/tratamiento farmacológico , Diabetes Mellitus Tipo 2/prevención & control , Ésteres/uso terapéutico , Compuestos de Sulfhidrilo/uso terapéutico , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/epidemiología , Anciano , Anticolesterolemiantes/uso terapéutico , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Estudios de Cohortes , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estado Prediabético/complicaciones , Estado Prediabético/tratamiento farmacológico , Estado Prediabético/epidemiología , Estado Prediabético/patología , Factores de Riesgo , Conducta de Reducción del Riesgo

RESUMEN

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) concentration is inversely related to risk of major adverse cardiovascular events (MACE) in epidemiologic studies but is a poorer predictor of MACE in patients with established coronary heart disease. HDL particle concentration (HDLP) has been proposed as a better predictor of risk. We investigated whether HDLP is associated with risk of MACE after acute coronary syndrome (ACS). METHODS: The dal-Outcomes trial compared the CETP inhibitor dalcetrapib with placebo in patients with recent ACS. In a nested case-cohort analysis, total, large, medium, and small HDLPs were measured by nuclear magnetic resonance spectroscopy at baseline (4-12 weeks after ACS) in 476 cases with MACE and 902 controls. Hazard ratios (HRs; case-control) for 1-SD increment of HDLP or HDL-C at baseline were calculated with and without adjustment for demographic, clinical, laboratory, and treatment variables. Similarly, HRs for MACE were calculated for changes in HDLP or HDL-C from baseline to month 3 of assigned treatment. RESULTS: Over median follow-up of 28 months, the risk of MACE was not associated with baseline HDLP (adjusted HR = 0.98, 95% CI = 0.84-1.15, P = .81), any HDLP subclass, or HDL-C. Dalcetrapib increased HDL-C and total, medium, and large HDLP and decreased small HDLP but had no effect on MACE compared with placebo. There were no association of risk of MACE with change in HDLP or HDL-C and no interaction with assigned study treatment. CONCLUSIONS: Neither baseline HDLP nor the change in HDLP on treatment with dalcetrapib or placebo was associated with risk of MACE after ACS.

Asunto(s)

Síndrome Coronario Agudo/sangre , Angina Inestable/epidemiología , Enfermedad Coronaria/mortalidad , Hospitalización/estadística & datos numéricos , Lipoproteínas HDL/sangre , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/epidemiología , Síndrome Coronario Agudo/tratamiento farmacológico , Anciano , Amidas , Anticolesterolemiantes/uso terapéutico , Estudios de Casos y Controles , HDL-Colesterol/sangre , Ésteres , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Compuestos de Sulfhidrilo/uso terapéutico

RESUMEN

BACKGROUND: Despite major advances in prevention and treatment, coronary artery disease (CAD) remains the leading cause of death worldwide. Whereas many sources of data are available on the epidemiology of acute coronary syndromes, fewer datasets reflect the contemporary management and outcomes of stable CAD patients. HYPOTHESIS: A worldwide contemporary registry would improve our knowledge about stable CAD. The main objectives are to describe the demographics, clinical profile, contemporary management and outcomes of outpatients with stable CAD; to identify gaps between evidence and treatment; and to investigate long-term prognostic determinants. METHODS: CLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an ongoing international observational longitudinal registry. Stable CAD patients from 45 countries in Europe, Asia, America, Middle East, Australia and Africa were enrolled between November 2009 and June 2010. The inclusion criteria were previous myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischemia or prior revascularization procedure. The main exclusion criteria were serious non-cardiovascular disease, conditions interfering with life expectancy or severe other cardiovascular disease (including advanced heart failure). Follow-up visits were planned annually for up to 5 years, interspersed with 6-month telephone calls. RESULTS: Of the 32,703 patients enrolled, most (77.6%) were male, age (mean ± SD) was 64.2 ± 10.5 years, and 71.0% were receiving treatment for hypertension; mean ± SD resting heart rate was 68.2 ± 10.6 bpm. Patients were enrolled based on a history of myocardial infarction >3 months earlier (57.7%), having at least one stenosis >50% on coronary angiography (61.1%), proven symptomatic myocardial ischemia on non-invasive testing (23.1%), or history of percutaneous coronary intervention or coronary artery bypass graft (69.8%). Baseline characteristics were similar across the four subgroups identified by the four inclusion criteria. CONCLUSION: CLARIFY will provide a useful resource for understanding the current epidemiology of stable CAD.

Asunto(s)

Enfermedad de la Arteria Coronaria/terapia , Estenosis Coronaria/terapia , Infarto del Miocardio/terapia , Pacientes Ambulatorios , Sistema de Registros , África/epidemiología , Anciano , Asia/epidemiología , Australia/epidemiología , Comorbilidad , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/epidemiología , Europa (Continente)/epidemiología , Femenino , Estado de Salud , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/epidemiología , América del Norte/epidemiología , Estudios Prospectivos , Proyectos de Investigación , Factores Socioeconómicos , América del Sur/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Indias Occidentales/epidemiología

RESUMEN

BACKGROUND: Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk. METHODS AND RESULTS: To address this question, we examined data from the dal-OUTCOMES trial that compared the cholesteryl ester transfer protein inhibitor dalcetrapib with placebo, beginning 4 to 12 weeks after an index acute coronary syndrome. Patients with New York Heart Association class II (with LVEF <40%), III, or IV HF were excluded. Aldosterone was measured at randomization in 4073 patients. The primary outcome was a composite of coronary heart disease death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, or resuscitated cardiac arrest. Hospitalization for HF was a secondary endpoint. Over a median follow-up of 37 months, the primary outcome occurred in 366 patients (9.0%), and hospitalization for HF occurred in 72 patients (1.8%). There was no association between aldosterone and either the time to first occurrence of a primary outcome (hazard ratio for doubling of aldosterone 0.92, 95% confidence interval 0.78-1.09, P=0.34) or hospitalization for HF (hazard ratio 1.38, 95% CI 0.96-1.99, P=0.08) in Cox regression models adjusted for covariates. CONCLUSIONS: In patients with recent acute coronary syndrome but without advanced HF, aldosterone does not predict major cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00658515.

Asunto(s)

Síndrome Coronario Agudo/sangre , Aldosterona/sangre , Enfermedad Coronaria/mortalidad , Paro Cardíaco/epidemiología , Hospitalización/estadística & datos numéricos , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/epidemiología , Síndrome Coronario Agudo/tratamiento farmacológico , Anciano , Amidas , Angina Inestable/epidemiología , Anticolesterolemiantes/uso terapéutico , Enfermedades Cardiovasculares , Ésteres , Femenino , Paro Cardíaco/terapia , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Compuestos de Sulfhidrilo/uso terapéutico

RESUMEN

AIM: To determine the current prevalence and control of major cardiovascular risk factors in stable CAD outpatients worldwide. METHODS: We analysed variations in cardiovascular risk factors in stable CAD outpatients from CLARIFY, a 5-year observational longitudinal cohort study, in seven geographical zones (Western/Central Europe; Canada/South Africa/Australia/UK; Eastern Europe; Central/South America; Middle East; East Asia; and India). RESULTS: Patient presentation (N=32,954, mean age 64.2 years, 78% male) varied between zones, as did prevalence of risk factors (all p < 0.0001). Obesity ranged from 20% (East Asia) to 42% (Middle East), raised blood pressure from 28% (Central/South America and East Asia) to 48% (Eastern Europe), raised LDL cholesterol from 24% (Canada/South Africa/Australia/UK) to 65% (Eastern Europe), elevated heart rate (≥70 bpm) from 38% (Western/Central Europe) to 78% (India), diabetes from 17% (Eastern Europe) to 60% (Middle East), and smoking from 6% (Central/South America) to 19% (Eastern Europe). Aspirin and lipid-lowering drugs were widely used everywhere (≥84% and ≥88%, respectively). Rates of risk factor control varied geographically (all p < 0.0001). Rate of controlled blood pressure in hypertension varied from 47% (Eastern Europe) to 66% (Central/South America), glucose control in diabetes from 23% (India) to 51% (Western/Central Europe and East Asia), controlled LDL cholesterol and dyslipidaemia from 32% (Eastern Europe) to 75% (Canada/South Africa/Australia/UK), heart rate <70 bpm from 22% (India) to 62% (Western/Central Europe), and heart rate ≤60 bpm in angina patients from 2% (India) to 29% (Canada/South Africa/Australia/UK and Central/South America). CONCLUSION: Prevalence and control of major cardiovascular risk factors in stable CAD vary markedly worldwide. Many stable CAD outpatients are being treated suboptimally.

Asunto(s)

Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/terapia , Disparidades en Atención de Salud/tendencias , Pacientes Ambulatorios , Pautas de la Práctica en Medicina/tendencias , Características de la Residencia , Conducta de Reducción del Riesgo , África/epidemiología , Anciano , Asia/epidemiología , Australia/epidemiología , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/mortalidad , Estudios Transversales , Europa (Continente)/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , América del Sur/epidemiología , Resultado del Tratamiento

RESUMEN

An elevated heart rate is an established marker of cardiovascular risk. Previous analyseshave suggested that ivabradine, a heart-rate–reducing agent, may improve outcomesin patients with stable coronary artery disease, left ventricular dysfunction,and a heart rate of 70 beats per minute or more.METHODSWe conducted a randomized, double-blind, placebo-controlled trial of ivabradine,added to standard background therapy, in 19,102 patients who had both stablecoronary artery disease without clinical heart failure and a heart rate of 70 beats perminute or more (including 12,049 patients with activity-limiting angina [class ≥II onthe Canadian Cardiovascular Society scale, which ranges from I to IV, with higherclasses indicating greater limitations on physical activity owing to angina]). Werandomly assigned patients to placebo or ivabradine, at a dose of up to 10 mg twicedaily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats perminute. The primary end point was a composite of death from cardiovascularcauses or nonfatal myocardial infarction.RESULTSAt 3 months, the mean (±SD) heart rate of the patients was 60.7±9.0 beats per minutein the ivabradine group versus 70.6±10.1 beats per minute in the placebo group.After a median follow-up of 27.8 months, there was no significant difference betweenthe ivabradine group and the placebo group in the incidence of the primaryend point (6.8% and 6.4%, respectively; hazard ratio, 1.08; 95% confidence interval,0.96 to 1.20; P=0.20), nor were there significant differences in the incidences ofdeath from cardiovascular causes and nonfatal myocardial infarction. Ivabradinewas associated with an increase in the incidence of the primary end point amongpatients with activity-limiting angina but not among those without activity-limitingangina (P=0.02 for interaction). The incidence of bradycardia was higher with ivabradinethan with placebo (18.0% vs. 2.3%, P<0.001)...

Asunto(s)

Disfunción Ventricular , Enfermedad de la Arteria Coronaria , Frecuencia Cardíaca

RESUMEN

OBJECTIVES: To determine the perioperative predictors of long-term mortality after aortic valve replacement (AVR). The authors hypothesized that perioperative variables are more important predictors of mortality than patient-prosthesis mismatch (PPM). DESIGN: A retrospective study of prospectively collected data. SETTING: A tertiary care university hospital. PARTICIPANTS: One-hundred-ninety-nine adult patients who underwent AVR. INTERVENTIONS: After Research and Ethics Committee approval, the authors studied consecutive adult patients that underwent AVR in 1999 from the time of procedure to 5 years later. Demographic data, hemodynamic profile obtained after the induction of anesthesia, and perioperative data were analyzed. Primary endpoint was 5-year survival. MEASUREMENTS AND MAIN RESULTS: Actuarial survival rate was 95.98%, 91.46%, and 81.91% at 30 days, 1 year, and 5 years, respectively. On univariate analysis, patients who died were significantly older (p<0.0001), had pulmonary hypertension (PHT), longer cardiopulmonary bypass (CPB) (p = 0.0001) and cross-clamping duration (p = 0.003), more frequent return to CPB (p = 0.036), or the use of an intra-aortic balloon pump to wean from CPB (p = 0.015). PPM was not related to 5-year mortality (p = 0.0649). Using Cox survival analysis, the only independent risk factors related to 5-year mortality after AVR were PHT using the mean arterial pressure-to-mean pulmonary artery pressure ratio (HR: 1.39, 95% CI 1.01-1.92, p = 0.0413) and the presence of complex separation from CPB (HR: 2.66, 95% CI 1.08-6.50, p = 0.0324). CONCLUSIONS: In patients undergoing AVR, 5-year survival was mostly related to the severity of PHT and intraoperative factors, mainly complexity of weaning from CPB.

Asunto(s)

Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas , Análisis Actuarial , Factores de Edad , Anciano , Anestesia General , Cateterismo de Swan-Ganz , Determinación de Punto Final , Femenino , Estudios de Seguimiento , Hemodinámica/fisiología , Humanos , Hipertensión Pulmonar/complicaciones , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Diseño de Prótesis , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Análisis de Supervivencia , Termodilución , Vasoconstrictores/uso terapéutico