RESUMEN
UNLABELLED: The aim of the study was to evaluate in general practice, in a large and unselected population of patients, the efficacy and safety of benazepril associated or not with hydrochlorothiazide (HCTZ) and to identify clinical and demographic predictive factors of antihypertensive efficacy. In this open uncontrolled study, 16,987 patients with mild to moderate hypertension were included by 5350 GPs. They received benazepril (BNZ) 10 mg once daily for 8 weeks. If sitting DBP remained > 90 mmHg after 4 weeks, HCTZ 12.5 mg once a day was then added for the last 4 weeks. RESULTS: In the intent to treat analysis, 54.5% of patients, after 4 weeks, and 80.6% of patients after 8 weeks, were controlled (DBP < 90 mmHg). Mean sitting DBP decreased from 100.5 +/- 5.5 mmHg (baseline) to 86.7 +/- 7.5 mmHg after 4 weeks and to 82.5 +/- 6.5 mmHg after 8 weeks. Mean SBP decreased from 169.5 +/- 13.1 mmHg to 150.5 +/- 12.5 mmHg after 4 weeks and to 145.0 +/- 10.9 mmHg after 8 weeks. Of the 16,900 patients included in the safety analysis, 853 (5.0%) dropped out of the study, 504 (3.0%) for adverse events (AE). The most frequent AE were: cough (3.5%), headache (0.9%), dizziness (0.8%), asthenia (0.6%) and nausea (0.5%). 13 deaths were observed during the study, mainly due to stroke or cancer. Six cases of raised serum creatinine level, 3 cases of angio-oedema and 2 cases of hepatitis were also reported. After 8 weeks of treatment, the main predictors of therapeutic response (DBP) were: recently discovered hypertension (86.3% of controlled DBP), regular exercise (85.5%) and age < 50 years (84.6%). Conversely: obesity, diabetes mellitus (77.9%), previously treated with several drugs (75.2%) and initial DBP > or = 105 mmHg (74.5%) were not predictive. Predictive factors emerging from logistic regression were : baseline DBP (< 105 mmHg), history of hypertension, body mass index, initial treatment of hypertension (no treatment--one drug--several drugs) and age. CONCLUSION: This large-scale study confirms, the antihypertensive efficacy and good tolerability of benazepril alone or associated with hydrochlorothiazide in general practice.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Benzazepinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Benzazepinas/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Índice de Severidad de la EnfermedadRESUMEN
The aim of this study was to define factors predictive of the onset of the terminal phase, defined by hyperbilirubinemia or the occurrence of a severe clinical complication, in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. The 97 primary biliary cirrhosis patients in this study participated in a 2-yr clinical trial. Four of the 49 patients treated with ursodeoxycholic acid (13 to 15 mg/kg/day) entered the terminal phase of the disease, compared with 9 of the 48 patients assigned to placebo. In addition to clinical, conventional biological and histological parameters, we analyzed three serum markers of connective tissue components--type III procollagen aminoterminal peptide, hyaluronic acid and laminin. In the ursodeoxycholic acid-treated group, hyaluronic acid, type III procollagen aminoterminal peptide, bilirubin and splenomegaly were the factors most closely associated with entry into the terminal phase of the disease. In multivariate analysis, after adjustment for age, the hyaluronic acid level was the only predictive factor. In the placebo-treated group, the bilirubin level, total bile acid level, Mayo score, type III procollagen aminoterminal peptide, hyaluronic acid, splenomegaly and pruritus were associated with aggravation of disease. In multivariate analysis, high bilirubin level, high type III procollagen aminoterminal peptide or hyaluronic acid levels and low prothrombin time independently implied poor prognosis. In conclusion, when patients with primary biliary cirrhosis are treated with ursodeoxycholic acid, bilirubinemia loses, in part, its predictive value. It is replaced by hyaluronic acid and type III procollagen aminoterminal peptide. This suggests that models used in deciding on the need for liver transplantation require adaptation for patients receiving ursodeoxycholic acid.
Asunto(s)
Tejido Conectivo/metabolismo , Cirrosis Hepática Biliar/tratamiento farmacológico , Cirrosis Hepática Biliar/fisiopatología , Ácido Ursodesoxicólico/uso terapéutico , Adulto , Anciano , Biomarcadores/sangre , Femenino , Predicción , Humanos , Hiperbilirrubinemia/etiología , Cirrosis Hepática Biliar/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Placebos , Análisis de SupervivenciaRESUMEN
The aim of the study was to evaluate efficacy of benazepril prescribed as replacement therapy in patients with mild to moderate hypertension, according to the pharmacological class of the previous unsuccessful drug. After wash-out of the ineffective or badly tolerated medication, 814 patients were randomly and blindly assigned to receive either benazepril 10 mg (group 1), benazepril 20 mg (group 2) or benazepril 10 mg plus hydrocholorothiazide 12.5 mg (group 3) once daily. The mean DBP changes from baseline were highly significant in each group (p < 0.001), and greater in groups 2 and 3 versus group 1 (p = 0.003). There was a non-significant trend for a greater efficacy of benazepril when the previous therapy was a diuretic or a calcium inhibitor. In this study, benazepril appears to be efficient as replacement therapy in moderate hypertension, but no link was demonstrated between the quality of the result and the nature of the previous drug.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Benzazepinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/clasificación , Antihipertensivos/uso terapéutico , Benzazepinas/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Insuficiencia del TratamientoRESUMEN
Severe alcoholic hepatitis is still a therapeutic challenge. It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate. A multicenter, randomized, single-blind, sequential trial was designed to compare this treatment with placebo. The triangular boundary was defined with alpha = 0.05, beta = 0.10 and estimated survival at 4 wk of 50% with placebo, 75% with treatment. Patients with biopsy-proven severe alcoholic hepatitis (presence of one or more of three criteria: encephalopathy, prothrombin activity less than or equal to 50%, bilirubinemia greater than or equal to 100 mumol/L) were randomized into two groups; one treatment group received an infusion (12 hr/day) of an association of insulin (30 IU) and glucagon (3 mg), and a control group received an infusion of glucose. Treatments were administered during a 3-wk period, and the mortality rate was noted at 4 wk. The decision to discontinue the trial was reached on the basis of results from the first 44 patients. Overall results were assessed in the 72 patients included at the time of this decision (treatment group: n = 37; control group: n = 35). Fifty-three patients had cirrhosis. No significant differences were noted between the two groups at inclusion on the basis of clinical, laboratory and histological criteria. The mortality rate was not significantly different in the two groups; 10 patients (27%) in the treatment group and 5 patients (14%) in the control group died. Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage, hepatic failure and infectious events.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Glucagón/uso terapéutico , Hepatitis Alcohólica/tratamiento farmacológico , Insulina/uso terapéutico , Adulto , Combinación de Medicamentos , Predicción , Hepatitis Alcohólica/mortalidad , Hepatitis Alcohólica/fisiopatología , Humanos , Infusiones Intravenosas , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
The fact that only a small percentage of excessive drinkers develop cirrhosis may be due to a genetic susceptibility to the disease. In order to identify possible genetic risk factors for cirrhosis, we studied mixed-race (Negroid-Caucasian) inhabitants of the French West Indies and compared: (1) the frequency of 51 HLA-A, -B, -C and -DR antigens in 41 subjects with alcoholic cirrhosis and in two control groups consisting of 41 excessive drinkers free of liver disease and 51 healthy non-drinkers; and (2) the frequency of Gm and Km haplotypes in the same groups. Analysis of the Gm system also determined the patients' ethnic origins. The frequency of the HLA-A2 antigen was significantly higher in the cirrhotic patients than in the control group of excessive drinkers (chi 2 = 4.47; P less than 0.05), while that of the HLA-B15 antigen was significantly lower (chi 2 = 5.14; P less than 0.05). The frequency of the Cw4 antigen was significantly higher in the cirrhotics than in the non-drinkers (chi 2 = 5.59; P less than 0.05). However, these differences did not persist when the number of comparisons was taken into account. The frequency of Gm and Km haplotypes was not significantly different in the three groups. In conclusion, complementary studies are required to determine the value of the Gm-Km system as a marker of susceptibility to alcoholic cirrhosis. Our results do not identify an association between HLA antigens and cirrhosis specific to a negroid ethnic group and support the notion that such an association is weak.
Asunto(s)
Población Negra/genética , Antígenos HLA/análisis , Alotipos de Inmunoglobulina Gm/análisis , Cadenas kappa de Inmunoglobulina/análisis , Cirrosis Hepática Alcohólica/inmunología , Población Blanca/genética , Adulto , Anciano , Biomarcadores/sangre , Susceptibilidad a Enfermedades , Femenino , Antígeno HLA-A2/análisis , Antígenos HLA-B/análisis , Antígeno HLA-B15 , Antígenos HLA-C/análisis , Humanos , Cirrosis Hepática Alcohólica/etnología , Masculino , Persona de Mediana Edad , Indias OccidentalesRESUMEN
From October 1977 to December 1983, estrogen receptor (ER) and progesterone receptor (PR) levels were measured in 645 tumors from women with primary, unilateral, nonmetastatic breast cancer. All of them were treated surgically. Some received adjuvant radiotherapy, adjuvant chemotherapy, or adjuvant hormonotherapy. A level of greater than 5 fmol/mg cytosolic protein was considered as positive for both ER and PR. Unifactorial analysis, using Kaplan and Meier estimates and the log-rank test, revealed that disease-free survival (DFS) and overall survival (SV) were both strongly related to age, tumor size, nodal status, nodal effraction, histopathologic grading (SBR), ER, and PR. Menopausal status and number of intramammary tumor foci were not significant. Multifactorial analysis, using Cox's model, revealed a strong relationship between SV and age (poor prognosis [pp]: less than or equal to 37 years old), menopausal status (pp: postmenopausal) tumor size, nodal status (pp: N+ greater than 3), nodal effraction, ER (pp: less than or equal to 5 fmol/mg), histopathologic grading (pp: SBR = 3), and PR (pp: less than or equal to 5 fmol/mg). Similarly, multifactorial analysis revealed a strong correlation between DFS and age, tumor size, nodal status, nodal effraction, histopathologic grading, and PR. A prognostic score taking into account these prognostic factors was calculated for DFS and SV. Analysis of this score allowed us to divide our patients into four significantly different (P less than 0.0001) groups with high, intermediate, and low risk of relapse. Our procedure was then validated using the sample test technique. These results show that both ER and PR have their own prognostic weight and should be considered, among other classic prognostic factors, when adjuvant therapies are indicated after surgical treatment of breast cancer.