RESUMEN
BACKGROUND: The TRANSFER-AMI study demonstrated that early routine percutaneous coronary intervention post-fibrinolysis (pharmacoinvasive strategy) is superior to conservative management for ST-elevation myocardial infarction. However, it is not clear whether treatment efficacy differs between men and women. METHODS: In this pre-specified subgroup analysis, we compared the efficacy of a pharmacoinvasive strategy in men versus women with acute ST-elevation myocardial infarction who were randomized to a pharmacoinvasive versus standard management following fibrinolysis. The primary end point was a composite of death, recurrent myocardial infarction, recurrent ischemia, heart failure and shock at 30 days. We tested for treatment heterogeneity between men and women using the Breslow-Day test. We also performed multivariable analysis adjusting for GRACE risk score and its interaction with treatment assignment, and evaluated for death/recurrent myocardial reinfarction as a secondary outcome. RESULTS: Of the 1059 patients, 843 were men and 216 were women. Compared to men, women were older, had worse Killip class, higher GRACE risk score, and higher rates of death and death/myocardial reinfarction at 30 days. The primary end point did not differ significantly between men and women (13.4% vs 16.7%, P = .22). Compared to standard treatment, a pharmacoinvasive strategy was associated with a lower rate of the primary end point in men (17.5% vs 9.4%, respectively, P < .001), but not in women (16.2% vs 17.1%, P = .86). There was a trend toward an interaction between treatment assignment and sex for the composite primary end point (P = .06). After adjustment for the significant interaction between GRACE risk score and treatment (P < .001), there was no significant interaction between sex and treatment for all the end points (all P > .40). CONCLUSION: The borderline heterogeneity in treatment efficacy of a pharmacoinvasive strategy in men versus women was no longer evident after adjustment for the difference in baseline risk. This suggests that sex per se was not an important determinant of the efficacy of a pharmacoinvasive strategy. Owing to the small number of women in this trial, further study in this area is needed.
Asunto(s)
Fibrinólisis , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea , Stents , Anciano , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores Sexuales , Resultado del TratamientoRESUMEN
Obesity is associated with hypertension, dyslipidemia, and diabetes, but it is also an independent cardiovascular risk factor. We sought to evaluate the differences in treatment patterns and attainment of guideline-recommended targets among high-risk vascular outpatients in relation to their body mass index (BMI). The prospective Vascular Protection and Guideline Orientated Approach to Lipid Lowering Registries recruited 7,357 high-risk vascular outpatients in Canada from 2001 to 2004. We stratified the patient population into 3 groups according to their BMI: normal weight (BMI <24.9 kg/m²), overweight (BMI 25 to 29.9 kg/m²), and obese (BMI >30 kg/m²). We evaluated the rates of attainment for contemporary guideline targets of blood pressure (<140/90 or <130/80 mm Hg in the presence of diabetes) and lipids (low-density lipoprotein [LDL] <2.5 mmol/L [96.7 mg/dl] and total cholesterol [TC]/high-density lipoprotein [HDL] ratio <4.0). Of the 7,357 patients, 1,305 (17.7%) were normal weight, 2,791 (37.9%) overweight, and 3,261 (44.4%) obese, as determined by the BMI. Obese patients were younger and more likely to have hypertension and diabetes (all p <0.001 for trend). Obese patients had higher baseline blood pressure, TC, LDL cholesterol, triglyceride levels and TC/HDL ratio, and lower HDL cholesterol. Obese patients were more likely to be treated with antihypertensive agents (p = 0.002), angiotensin-converting enzyme inhibitors (p = 0.024), angiotensin receptor blockers (p <0.001), and high-dose statin therapy (p = 0.001). On multivariable analyses, obese patients were less likely to attain the blood pressure (odds ratio 0.77, 95% confidence interval 0.66 to 0.90, p = 0.001) and TC/HDL ratio (odds ratio 0.48, 95% confidence interval 0.42 to 0.55, p <0.001) targets but not the LDL targets (odds ratio 0.89, 95% confidence interval 0.78 to 1.03, p = 0.11). In conclusion, only a minority ambulatory patients at high cardiovascular risk achieved both guideline-recommended blood pressure and lipid targets, and this significant treatment gap was more pronounced among obese patients. Our findings underscore the opportunity to optimize the treatment of these high-risk patients.
Asunto(s)
Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Hiperlipidemias/sangre , Hiperlipidemias/etiología , Hipertensión/sangre , Hipertensión/etiología , Obesidad/sangre , Obesidad/complicaciones , Sobrepeso/sangre , Sobrepeso/complicaciones , Anciano , Índice de Masa Corporal , Distribución de Chi-Cuadrado , Estudios Transversales , Diabetes Mellitus/sangre , Diabetes Mellitus/etiología , Femenino , Humanos , Lípidos/sangre , Masculino , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Sistema de Registros , Factores de RiesgoRESUMEN
Guidelines recommend that > or =50% of patients starting dialysis have a fistula. We reviewed our experience in consecutive incident patients over a 1-year period. Only 30 of the 93 patients starting hemodialysis had a fistula that was accessed. Late referral (nephrology contact <90 days) was a significant issue in 48% (30/63) of the patients without a fistula. Most (n=21) of the late referrals were acute disease; only 9 were late referrals of chronic disease. Nephrology follow-up exceeded 200 days in the remaining (33/63) without this access. In the cohort with sufficient nephrology referral, we explored variables associated with a fistula (n=30) compared with those without one (n=33). In multivariate logistic regression analysis, peripheral vascular disease (odds ratio [OR] 0.026, 95% confidence interval [CI] 0.002-0.286) and rapid loss of estimated glomerular filtration rate (eGFR) (OR 0.745 per mL/min/1.73 m(2)/year, 95% CI 0.625-0.888) in the year preceding dialysis were significant negative predictors for a fistula. Patients without access experienced faster declines in GFR in the year preceding dialysis (12.1+/-9.9 vs. 4.7+/-3.5 mL/min 1.73 m(2) with access, p<0.001). Glomerular filtration rate loss in the 2 years before starting dialysis was the same between the 2 groups (-0.54+/-10.4 vs. 1.42+/-3.9 mL/min 1.73 m(2)). Age, sex, diabetes, other comorbidity, length of nephrology follow-up, eGFR at dialysis start, hemoglobin, and albumin were not significant. At our center, rapid loss of renal function in otherwise stable chronic kidney disease (CKD) patients is more important than late referral of CKD for the lack of access. Improvements in rapid referral for access creation could help reduce this barrier.
Asunto(s)
Cateterismo , Tasa de Filtración Glomerular , Diálisis Renal , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Adulto , Anciano , Cateterismo/efectos adversos , Catéteres de Permanencia/efectos adversos , Femenino , Estudios de Seguimiento , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Albúmina Sérica/análisis , Enfermedades Vasculares/sangre , Enfermedades Vasculares/etiología , Enfermedades Vasculares/fisiopatologíaRESUMEN
Paclitaxel (Taxol) is a drug that is commonly used in the treatment of metastatic breast cancer. In this study, we investigated the effect of prior exposure to submaximal cytotoxic concentrations (EC(25) and EC(50)) of paclitaxel on the subsequent ability of human Jurkat T lymphocytes to adhere to monolayers of MDA-MB-435 human breast carcinoma cells. Jurkat T cells that survived culture for 24 h in the presence of paclitaxel (0.1 or 3 micro g/ml) exhibited a diminished ability to adhere to MDA-MB-435 breast cancer cell monolayers. Flow cytometric analysis of paclitaxel-treated Jurkat T cells revealed reduced surface expression of alphaL, alpha4, alpha5, and beta7 integrins, but normal beta1 integrin expression. These data suggest that paclitaxel interferes with the expression of alphaLbeta2 (LFA-1), alpha4beta1 (VLA-4), alpha5beta1 (VLA-5), and alpha4beta7 (LPAM-1) adhesion molecules by surviving T cells. Blocking experiments with antibodies against alphaL, alpha4, alpha5, beta1, and beta7 integrins revealed that adhesion of Jurkat T cells to MDA-MB-435 breast cancer cell monolayers was dependent upon alphaL, alpha4, and beta7 but not alpha5 or beta1 integrins. We conclude that prior exposure to paclitaxel caused a reduction in Jurkat T cell adhesion to MDA-MB-435 breast carcinoma cells by preventing optimal alphaLbeta2 and alpha4beta7 interactions with their corresponding ligands on tumor cells. A similar effect by paclitaxel on T lymphocytes of breast cancer patients may compromise cell-mediated anti-tumor immune responses.