RESUMEN
This prospective, double-blind, randomised, parallel-group, multicentre study assessed the adjunctive effect of telmisartan monotherapy versus placebo in controlling blood pressure during the last six hours of the 24-hour dosing period. After a two-week run-in phase, 375 patients with essential hypertension uncontrolled on existing therapy were randomised to either placebo or telmisartan (40 mg uptitrated to 80 mg after four weeks, if needed) for eight weeks. Ambulatory blood pressure monitoring (ABPM) was conducted at randomisation (baseline) and treatment end. The change from baseline in diastolic blood pressure (DBP) over the last six hours (primary endpoint) was significantly greater with telmisartan than placebo (adjusted mean treatment difference in favour of telmisartan: -3.7 mmHg, 95% confidence interval (CI) -5.5, -1.9 mmHg, p < or = 0.001, n = 350), as was the reduction in 24-hour DBP (adjusted mean treatment difference: -5.0 mmHg, 95% CI -6.5, -3.5 mmHg, p < or = 0.001). Telmisartan also reduced mean systolic blood pressure significantly more than placebo over the last six hours and the entire 24-hour dosing interval. Responder rates (ABPM DBP, seated DBP, and overall [seated SBP/DBP]) at 8 weeks were significantly higher with telmisartan than with placebo (p < or = 0.01). All treatments were well tolerated. When added to existing antihypertensive regimens, telmisartan offers additional effectiveness while maintaining placebo-like tolerability.
Asunto(s)
Antihipertensivos/administración & dosificación , Bencimidazoles/administración & dosificación , Benzoatos/administración & dosificación , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Antihipertensivos/efectos adversos , Bencimidazoles/efectos adversos , Benzoatos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Monitoreo Ambulatorio de la Presión Arterial , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , TelmisartánRESUMEN
OBJECTIVE: At higher doses, simvastatin has been shown to produce significantly greater increases in high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I than atorvastatin. To extend and confirm these findings, a 36-week, randomized, double-blind, dose-titration study was performed in 826 hypercholesterolemic patients to compare the effects of simvastatin and atorvastatin on HDL cholesterol, apo A-I, and clinical and laboratory safety. PRIMARY HYPOTHESIS: Simvastatin, across a range of doses, will be more effective than atorvastatin at raising HDL cholesterol and apo A-I levels. METHODS: A total of 826 hypercholesterolemic patients were enrolled in this double-blind, randomized, parallel, 36-week, dose-escalation study. Patients randomized to simvastatin received 40 mg/day for the first 6 weeks, 80 mg/day for the next 6 weeks, and remained on 80 mg/day for the final 24 weeks. Patients randomized to atorvastatin received 20 mg/day for the first 6 weeks, 40 mg/day for the next 6 weeks, and 80 mg/day for the remaining 24 weeks. RESULTS: During the first 12 weeks of the study, simvastatin increased HDL cholesterol and apo A-I more than the comparative doses of atorvastatin, while producing slightly lower reductions in low-density lipoprotein (LDL) cholesterol and triglycerides. At the maximal dose comparison, simvastatin 80 mg and atorvastatin 80 mg, the HDL cholesterol and apo A-I differences favoring simvastatin were larger than at the lower doses. In addition, at the maximal dose comparison, the incidence of drug-related clinical adverse experiences was approximately two-fold higher with atorvastatin 80 mg than with simvastatin 80 mg (23 versus 12%, p < 0.001), due predominantly to a greater incidence of gastrointestinal symptoms with atorvastatin (10 versus 3%, p < 0.001). The incidence of clinically significant alanine aminotransferase elevations was also higher with atorvastatin 80 mg than with simvastatin 80 mg (3.8 versus 0.5%, p < 0.010), especially in women (6.0 versus 0.6%). CONCLUSIONS: At the doses compared in this study, simvastatin led to greater increases in HDL cholesterol and apo A-I levels than atorvastatin. At the maximum dose comparison, there were fewer drug-related gastrointestinal symptoms and clinically significant aminotransferase elevations with simvastatin.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Lípidos/sangre , Pirroles/uso terapéutico , Simvastatina/uso terapéutico , Adulto , Anciano , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , Apolipoproteína A-I/sangre , Atorvastatina , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Método Doble Ciego , Femenino , Ácidos Heptanoicos/administración & dosificación , Ácidos Heptanoicos/efectos adversos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hipercolesterolemia/sangre , Masculino , Persona de Mediana Edad , Pirroles/administración & dosificación , Pirroles/efectos adversos , Simvastatina/administración & dosificación , Simvastatina/efectos adversos , Resultado del Tratamiento , Estados UnidosRESUMEN
Intracardiac left-to-right shunting may be detected and quantitated by an oximetric analysis of blood from the right-sided cardiac chambers and prominent early recirculation of indocyanine green after it is injected into the central venous circulation and sampled from a systemic artery. Although the variability of oximetric measurements has been established in patients without shunting and a range of normal has been determined for the technique, the variability of the indocyanine green method among persons without shunting has not been clarified; as a result, a range of normal for indocyanine green has not been established. In 66 adult patients in whom hydrogen inhalation (an extremely sensitive technique for detecting even very small intracardiac left-to-right shunts) revealed no shunting, indocyanine green curves were generated by injection into the pulmonary artery as blood was sampled from a systemic artery. In these patients the percentage left-to-right shunt (that is, the percentage of pulmonary blood flow reaching the lungs through an intracardiac shunt) (determined with the equation of Carter et al) ranged from -9% to +26% (+7 +/- 8%, mean +/- standard deviation). There was no definable relation between the percentage left-to-right shunt and the indicator dilution measurement of cardiac output. Thus, these data establish a range of normal for the indocyanine green technique of detecting and measuring intracardiac left-to-right shunting. If this technique is to be used reliably to detect shunting, its results must demonstrate a percentage shunt in excess of +26%.
Asunto(s)
Defectos de los Tabiques Cardíacos/diagnóstico , Verde de Indocianina , Adulto , Anciano , Gasto Cardíaco , Técnica de Dilución de Colorante , Femenino , Humanos , Hidrógeno , Masculino , Persona de Mediana Edad , Oximetría , Estudios Prospectivos , Valores de ReferenciaRESUMEN
Through the use of a quantitative solution hybridization assay with 32P-labeled cDNA probes, we found that mevinolin, an inhibitor of cholesterol synthesis, elevates the level of mRNA for the low density lipoprotein receptor in livers of hamsters and rabbits. In hamsters the maximal effect (3-fold increase) occurred at 0.1% mevinolin in the diet for 10 days. The same dose produced a maximal induction (10-fold) of mRNA levels for 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of cholesterol synthesis, and a maximal decrease (80%) in plasma cholesterol. The drug lowered the level of all cholesterol-carrying lipoproteins in plasma. In normal rabbits, mevinolin produced a 90% reduction in plasma low density lipoprotein-cholesterol levels, which was associated with a 2.5-fold increase in low density lipoprotein receptor mRNA levels. A similar induction of receptor mRNA occurred in livers of Watanabe-heritable hyperlipidemic rabbits, although the plasma cholesterol was not reduced to normal, presumably because the receptors produced by the mutant mRNA function poorly. These data are consistent with the hypothesis that mevinolin and other inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase lower plasma cholesterol levels in part by stimulating production of mRNA for the low density lipoprotein receptor in liver.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hígado/metabolismo , Naftalenos/farmacología , ARN Mensajero/biosíntesis , Receptores de LDL/genética , Animales , Colesterol/sangre , Cricetinae , Femenino , Lipoproteínas/sangre , Lovastatina , Masculino , Mesocricetus , Conejos , Receptores de LDL/efectos de los fármacosRESUMEN
Pharmacologic doses of 17 alpha-ethinyl estradiol are known to increase the number of low density lipoprotein (LDL) receptors in livers of rats, thereby producing a profound fall in plasma cholesterol levels. We now report that ethinyl estradiol exerts the same effect in livers of male and female rabbits and that the increase in receptor number is correlated with a 6- to 8-fold increase in the levels of receptor mRNA. Receptor protein was measured by ligand blotting, and mRNA levels were measured by a quantitative solution hybridization/S1 nuclease protection assay using uniformly 32P-labeled single-stranded cDNA probes. These experiments demonstrate that pharmacologic induction of the mRNA for the LDL receptor in liver can lead to increased LDL receptor levels and a fall in plasma cholesterol in experimental animals.
Asunto(s)
Etinilestradiol/farmacología , Hígado/efectos de los fármacos , ARN Mensajero/análisis , Receptores de LDL/genética , Animales , Colesterol/sangre , ADN/metabolismo , Femenino , Hígado/análisis , Hígado/metabolismo , Masculino , Hibridación de Ácido Nucleico , Poli A/metabolismo , ARN/metabolismo , Conejos , Receptores de LDL/análisis , Receptores de LDL/metabolismoRESUMEN
Chemoprophylaxis and disinfection of the operation site for the prevention of bacteriuria after a transurethral operation were assessed in controlled, prospective studies in men with sterile urine preoperatively. The majority of the control patients (65 per cent) suffered postoperative bacteriuria compared to 38.6 per cent after perioperative disinfection with chlorhexidine and 10 per cent or less after each of 2 other regimens (intramuscular cephradine followed by oral nitrofurantoin and chlorhexidine disinfection followed by oral nitrofurantoin). The latter regimen is preferred since it avoids the use of agents with systemic action.