RESUMEN
OBJECTIVE: To investigate the effect of dutasteride versus placebo on the symptoms and associated complications of male lower urinary tract symptoms and benign prostatic hyperplasia (BPH) across a range of prostate volumes and BPH symptoms in men evaluated for prostate cancer risk reduction in the 4-year REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. METHODS: REDUCE was a multicenter, randomized, double-blind, placebo-controlled study of prostate cancer risk reduction with daily dutasteride 0.5 mg or placebo. Eligible men were aged 50-75 years, with a prostate-specific antigen level of 2.5-10 ng/mL and a prostate volume of ≤80 cm3. The prespecified and post hoc analyses were performed on the incidence of acute urinary retention, BPH-related surgery, and urinary tract infections, as well as on changes in prostate volume, International Prostate Symptom Score, BPH Impact Index, and maximal urinary flow rate (Qmax). RESULTS: A total of 8122 men were included in the efficacy population. During the 4-year study, the International Prostate Symptom Score increased in placebo-treated patients, while dutasteride-treated patients had a stabilized or decreased International Prostate Symptom Score and improved BPH Impact Index and quality of life due to urinary symptom scores across all prostate volume quintiles (including prostate glands smaller than those studied in previous dutasteride trials). 48 months, the incidence of acute urinary retention or BPH-related surgery was significantly less in the dutasteride group (2.5%) than in the placebo group (9%) overall (P<.001) and in each baseline prostate volume quintile (P<.01). CONCLUSION: During the 4-year study, dutasteride was associated with a decreased risk of BPH progression in men with mild-to-moderate symptoms and normal or enlarged prostates.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/administración & dosificación , Azaesteroides/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Neoplasias de la Próstata/prevención & control , Anciano , Método Doble Ciego , Dutasterida , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Próstata/patología , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/patología , Neoplasias de la Próstata/etiología , Conducta de Reducción del Riesgo , Retención Urinaria/etiologíaRESUMEN
OBJECTIVE: ⢠To investigate the influence of baseline variables on the 4-year incidence of acute urinary retention (AUR), benign prostatic hyperplasia (BPH)-related surgery and overall clinical progression in men treated with tamsulosin, dutasteride, or a combination of both. PATIENTS AND METHODS: ⢠The 4-year Combination of Avodart® and Tamsulosin (CombAT) study was a multicenter, randomized, double-blind, parallel-group study of clinical outcomes in men aged ≥ 50 years with symptomatic (International Prostate Symptom Score [IPSS]≥ 12) BPH, with prostate-specific antigen (PSA) levels of ≥ 1.5 ng/mL and ≤ 10 ng/mL, and a prostate volume (PV) of ≥ 30 mL. ⢠Eligible patients received tamsulosin 0.4 mg, dutasteride 0.5 mg, or a combination of both. ⢠The primary endpoint was time to first AUR or BPH-related surgery. Secondary endpoints included clinical progression of BPH and symptoms. Posthoc analyses of the influence of baseline variables (including age, IPSS health-related quality of life [HRQL], PV, PSA, IPSS, peak urinary flow rate [Q(max) ] and body-mass index [BMI]) on the incidence of AUR or BPH-related surgery, clinical progression of BPH, and symptoms were performed. RESULTS: ⢠There were 4844 men in the intent-to-treat population. Overall baseline characteristics were similar across all patient groups. ⢠Regardless of baseline subgroup, the incidence of AUR or BPH-related surgery was higher in men treated with tamsulosin than in those treated with dutasteride or combined therapy. ⢠Combined therapy was statistically better than tamsulosin in reducing the risk of AUR or BPH-related surgery in subgroups of baseline PV > 42.0 mL, in all subgroups of baseline PSA level, and all other baseline subgroups (P ≤ 0.001). ⢠Across treatment groups, the incidence of clinical progression was highest in men with a baseline IPSS of < 20 or IPSS HRQL score of < 4. The incidence of clinical progression was also higher in men receiving tamsulosin than dutasteride or combined therapy in all baseline subgroups, except for men with a baseline PV of < 40 mL. Combined therapy reduced the relative risk (RR) of clinical progression compared with tamsulosin across all baseline subgroups and compared with dutasteride across most baseline subgroups. ⢠Symptom deterioration was the most common progression event in each treatment group regardless of baseline subgroup, except in those men with an IPSS of ≥ 20 at baseline. Combined therapy reduced the RR of symptom deterioration compared with tamsulosin across all but one baseline subgroup (the reduction was not significant for men with a baseline PV of < 40 mL) and compared with dutasteride in most subgroups. CONCLUSIONS: ⢠Men with a baseline PV of ≥ 40 mL and any baseline PSA level of ≥1.5 ng/mL had greater reductions in the RR of AUR or BPH-related surgery and greater reductions in the RR of clinical progression and symptom deterioration on combined therapy or dutasteride monotherapy than on tamsulosin monotherapy. ⢠These analyses support the long-term use of combined therapy with dutasteride plus tamsulosin in men with moderate-to-severe BPH symptoms and a slightly enlarged prostate.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/uso terapéutico , Azaesteroides/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Retención Urinaria/tratamiento farmacológico , Anciano , Quimioterapia Combinada/métodos , Dutasterida , Métodos Epidemiológicos , Humanos , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/cirugía , Tamsulosina , Resultado del Tratamiento , Retención Urinaria/etiología , Retención Urinaria/cirugíaRESUMEN
BACKGROUND: Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and prostatic enlargement. OBJECTIVE: To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention (AUR), BPH-related surgery, and BPH clinical progression over 4 yr in men at increased risk of progression. DESIGN, SETTING, AND PARTICIPANTS: The Combination of Avodart and Tamsulosin (CombAT) study was a 4-yr, multicenter, randomised, double-blind, parallel-group study in 4844 men > or =50 yr of age with a clinical diagnosis of BPH, International Prostate Symptom Score > or =12, prostate volume > or =30 cm(3), prostate-specific antigen 1.5-10 ng/ml, and maximum urinary flow rate (Q(max)) >5 and < or =15 ml/s with minimum voided volume > or =125 ml. INTERVENTION: Oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. MEASUREMENTS: The 4-yr primary end point was time to first AUR or BPH-related surgery. Secondary end points included BPH clinical progression, symptoms, Q(max), prostate volume, safety, and tolerability. RESULTS AND LIMITATIONS: Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery. Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression. Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr. Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies, with the exception of an imbalance in the composite term of cardiac failure among the three study arms. The lack of placebo control is a study limitation. CONCLUSIONS: The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement. CLINICALTRIALS.GOV IDENTIFIER: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).
Asunto(s)
Inhibidores de 5-alfa-Reductasa , Antagonistas Adrenérgicos alfa/uso terapéutico , Azaesteroides/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Antagonistas Adrenérgicos alfa/efectos adversos , Anciano , Azaesteroides/efectos adversos , Brasil , Progresión de la Enfermedad , Método Doble Ciego , Quimioterapia Combinada , Dutasterida , Inhibidores Enzimáticos/efectos adversos , Humanos , Italia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , América del Norte , Modelos de Riesgos Proporcionales , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/cirugía , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Sulfonamidas/efectos adversos , Tamsulosina , Factores de Tiempo , Resultado del Tratamiento , Retención Urinaria/tratamiento farmacológico , Retención Urinaria/etiología , Procedimientos Quirúrgicos Urológicos MasculinosRESUMEN
This article reports the results of a post hoc analysis of the multicenter, randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) study, which aimed to investigate the effects of dutasteride (0.5 mg), tamsulosin (0.4 mg), and their combination on storage and voiding symptoms in 4844 men aged > or =50 years with moderate-to-severe lower urinary tract symptoms (International Prostate Symptom Score > or =12), prostate volume (PV) > or =30 cm(3) and PSA 1.5-10 ng ml(-1). After 24 months, combination treatment achieved significantly greater mean reductions in both voiding and storage symptoms than either monotherapy, in each of the three baseline PV tertiles (30 to <42, 42 to <58, > or =58 cm(3)). Dutasteride was as effective as tamsulosin for control of storage symptoms, but provided significantly greater relief of voiding symptoms than tamsulosin.
Asunto(s)
Azaesteroides/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Prostatismo/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Micción/efectos de los fármacos , Antagonistas Adrenérgicos alfa/administración & dosificación , Antagonistas Adrenérgicos alfa/uso terapéutico , Anciano , Azaesteroides/administración & dosificación , Método Doble Ciego , Quimioterapia Combinada , Dutasterida , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Sulfonamidas/administración & dosificación , Tamsulosina , Vejiga Urinaria Hiperactiva/tratamiento farmacológicoRESUMEN
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1), thereby inhibiting platelet function via blockade of thromboxane A2 (TxA2) formation, and COX-2, the enzyme that mediates inflammatory responses. Meloxicam is a relatively COX-2-selective anti-arthritis drug that shows significant TxA2 inhibition, albeit less than traditional NSAIDs. A randomized, double-blind, placebo-controlled trial was conducted in 79 healthy adults to compare the effects of once-daily therapeutic (7.5 mg, 15 mg) and supratherapeutic (30 mg) doses of meloxicam with extended-release indomethacin (Indo-ER 75 mg once daily) on bleeding time, TxA2 formation, and platelet aggregation. The authors measured platelet aggregation to COX-1-dependent (ADP arachidonate) and COX-1-independent (high-dose collagen) agonists, bleeding time, serum TxB2, and clotting times (aPTT and PT) after 8 days' administration and at 3 and 6 hours after steady-state dosing. Meloxicam significantly decreased TxB2 production compared with placebo in a dose-dependent fashion, reaching a peak of 77% inhibition 6 hours after 30 mg meloxicam; Indo-ER blocked TxB2 formation by 96% at the same time point. However, neither acute nor 8 days' administration of meloxicam at any dose caused a significant increase in bleeding time or inhibition of platelet aggregation to any agonist when compared with placebo. By contrast, Indo-ER significantly increased the bleeding time and inhibited platelet aggregation to COX-1-dependent agonists 6 hours after dosing. Clotting times were unaffected by any drug. It was concluded that unlike nonselective NSAIDs, meloxicam's blockade of TxA2 formation (even at supratherapeutic doses) does not reach levels that result in decreased in vivo platelet function, as measured by bleeding time and aggregometry. In this study of healthy subjects, meloxicam did not interfere with platelet-mediated hemostasis.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Plaquetas/efectos de los fármacos , Tiazinas/farmacología , Tiazoles/farmacología , Adulto , Antiinflamatorios no Esteroideos/efectos adversos , Tiempo de Sangría , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/fisiología , Método Doble Ciego , Femenino , Hemorragia/inducido químicamente , Humanos , Indometacina/efectos adversos , Indometacina/farmacología , Masculino , Meloxicam , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Agregación Plaquetaria/efectos de los fármacos , Recuento de Plaquetas , Tiempo de Protrombina , Tiazinas/efectos adversos , Tiazoles/efectos adversos , Tromboxano B2/sangreRESUMEN
From 1969 to 1974, 2080 patients were sterilized, 1702 by the pelviscopic method (electrocoagulation), 375 by laparotomy, and 3 vaginally. About two thirds of the sterilisations by laparotomy were carried out after delivery or during other surgical procedures. 15% of all women were sterilized for medical reasons; the other cases had to be 35 years of age or at least 30 if they had more than 3 children. The overall complication rate was 5% with both methods. Complications during pelviscopy included hemorrhage, bowel injury and burns. Postoperative complications after laparotomy were hemorrhage, thrombosis and wound dehiscence. Only half of the patients could be followed up; there were 4 pregnancies among 1308 women. In more than 50% the sexual relations had improved, in only 3% they had worsened. About 97% of the pelviscopically sterilized patients were satisfied with surgical method chosen and with their present status. It is recommended to allow sufficient time to think the decision over prior to the operation.
PIP: A report on the complication rate from 1702 pelviscopic sterilizations and 378 laparotomy or colpotomy sterilizations is presented. 15.2% of the sterilizations were performed under the medical indication, and the average age of this group was less than that of the other patients. The complication rate for the patients undergoing pelviscopy was 4.98%; a laparotomy was made necessary in only .7% of the cases. Bleeding, slight burns, and pain were the most frequent complications. The complication rate for the laparotomy patients was 4.94%, mainly less serious complications such as slight bleeding, subcutaneous hematoma, or dehiscence of the wound occurred. 4 pregnancies were reported after the operations. 43.3% experienced changes in the menstrual cycle. 51.4% reported that their sexual relations had improved after the operation, 2.9% that they had gotten worse. 97% of the pelviscopy patients were satisfied with the operation.