The effects of combination therapy with dutasteride plus tamsulosin on clinical outcomes in men with symptomatic BPH: 4-year post hoc analysis of European men in the CombAT study.

CombAT (Combination of Avodart and Tamsulosin) was a randomised, double-blind study in men (n=4844) aged ≥ 50 years with a clinical diagnosis of BPH. Patients were randomised to daily tamsulosin 0.4 mg, dutasteride 0.5 mg or both for 4 years. The primary endpoint was time to acute urinary retention (AUR) or BPH-related surgery. Secondary endpoints included BPH clinical progression, symptoms and maximum urinary flow rate. A post hoc analysis of data from the European subgroup was conducted. A total of 2925 men were randomised to treatment in Europe as part of CombAT (tamsulosin, n=972; dutasteride, n=970; combination, n=983). Combination therapy significantly reduced the relative risk of AUR or BPH-related surgery compared with either monotherapy at 4 years, and also significantly reduced the risk of BPH clinical progression. Combination therapy also provided significantly greater symptom improvement than either monotherapy at 4 years. Safety and tolerability of dutasteride plus tamsulosin was consistent with previous experience of this combination and with the monotherapies. These data provide further evidence to support the use of long-term combination therapy (dutasteride plus tamsulosin) in men with moderate-to-severe lower urinary tract symptoms because of BPH and prostatic enlargement. The results in the European subgroup are generally consistent with those in the overall study population.

Effect of dutasteride, tamsulosin and the combination on patient-reported quality of life and treatment satisfaction in men with moderate-to-severe benign prostatic hyperplasia: 4-year data from the CombAT study.

OBJECTIVE: To investigate the effect of combination therapy with dutasteride plus tamsulosin compared with each monotherapy on patient-reported health outcomes over 4 years in men with moderate-to-severe lower urinary tract symptoms (LUTS) because of benign prostatic hyperplasia (BPH). METHODS: CombAT was a 4-year international, double-blind, randomised, parallel-group trial in men (n = 4844) with moderate-to-severe symptoms of BPH and at increased risk of disease progression [age > or = 50 years, International Prostate Symptom Score (IPSS) > or = 12, prostate volume > or = 30 cc, serum prostate-specific antigen > or = 1.5 ng/ml to < or = 10 ng/ml and maximum urinary flow rate 5-15 ml/s with minimum voided volume > or = 125 ml]. Subjects were randomised to receive 0.5 mg dutasteride, 0.4 mg tamsulosin or the combination once daily for 4 years. The primary endpoint at 4 years was the time to event and proportion of subjects with acute urinary retention or undergoing BPH-related prostate surgery. Secondary endpoints included the health-outcomes measures, BPH Impact Index (BII), IPSS question 8 (IPSS Q8) and the Patient Perception of Study Medication (PPSM) questionnaire. RESULTS: At 4 years, combination therapy resulted in significantly superior improvements from baseline in BII and IPSS Q8 than either monotherapy; these benefits were observed from 3 months onwards compared with dutasteride and from 9 months (BII) or 12 months (IPSS Q8) onwards compared with tamsulosin. Also at 4 years, the PPSM questionnaire showed that a significantly higher proportion of patients was satisfied with, and would request treatment with, combination therapy compared with either monotherapy. CONCLUSIONS: Combination therapy (dutasteride plus tamsulosin) provides significantly superior improvements in patient-reported quality of life and treatment satisfaction than either monotherapy at 4 years in men with moderate-to-severe BPH symptoms.

Efficacy and safety of dutasteride, tamsulosin and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate-to-severe BPH.

Although ethnicity-based differences in prostate size and physiology have been reported, results of benign prostatic hyperplasia (BPH) treatment trials in predominantly Caucasian patients are assumed to be applicable to non-Caucasian populations. This post hoc analysis investigated whether an Asian subpopulation of men with moderate-to-severe BPH in the CombAT study achieves treatment responses in line with those of the overall study population. In this double-blind, randomized, parallel-group trial, 325 Asian men were assigned to treatment with 0.5 mg dutasteride once daily, 0.4 mg tamsulosin once daily or the combination. Decrease in international prostate symptom score (IPSS) at month 24 from baseline (the primary endpoint) was significantly greater with combination treatment compared with tamsulosin (P<0.05), and numerically, but not statistically significantly, greater compared with dutasteride. Mean IPSS was reduced from baseline by 7.5 (+/-0.84) in the combination group, by 6.3 (+/-0.86) in the dutasteride group and by 4.5 (+/-0.78) in the tamsulosin group, resulting in respective mean IPSS at months 24 of 11.4 (+/-0.60), 12.7 (+/-0.70) and 14.3 (+/-0.74). The adverse event profile was similar to that observed in the overall CombAT population, and drug-related adverse events were more common with combination therapy (26%) than with tamsulosin (15%) or dutasteride (9%). No unexpected adverse events emerged. In conclusion, in Asian men with moderate-to-severe lower urinary tract symptoms and an enlarged prostate, combination therapy achieved significantly greater improvements from baseline BPH symptoms, flow rate, quality of life, reduced prostate volume and improved treatment satisfaction compared with tamsulosin monotherapy.

Intravenous dolasetron for the prevention of postoperative nausea and vomiting after outpatient laparoscopic gynecologic surgery.

The newer 5-hydroxytryptamine type 3 (5-HT3) antagonists are sometimes considered for routine prophylaxis of postoperative nausea and vomiting (PONV) in high-risk patients. This multicenter, randomized, double-blind, placebo-controlled study compared the efficacy and safety of three single intravenous (IV) doses of dolasetron mesylate salt (12.5, 25, or 50 mg) for the prevention of PONV in 635 females undergoing outpatient laparoscopic gynecologic surgery. Antiemetic efficacy was evaluated over a 24-h postoperative period by recording the number and timing of emetic episodes; effects on nausea were evaluated by a visual analog scale (VAS). The proportion of complete responders (no emetic episodes and no escape medication in 24 h) was significantly higher with each dolasetron mesylate dose (> 50% for each dose; P < or = 0.0003) than with placebo (30.6%). Fewer patients given dolasetron required or requested escape antiemetic medication compared with placebo (P < 0.0003). Dolasetron-treated patients had significantly (P < 0.0357) lower median postdose maximum nausea VAS scores compared with placebo-treated patients. Patient satisfaction with dolasetron was high and, overall, was significantly (P = 0.0131) greater than that with placebo. Dolasetron was an effective and well tolerated preventive treatment for PONV resulting from laparoscopic gynecologic surgery.

Ranitidine versus cimetidine in the healing of erosive esophagitis.

Ranitidine 150 mg twice daily (BID) is an approved therapeutic approach for relieving the symptoms of gastroesophageal reflux disease. Ranitidine 150 mg four times daily (QID) and cimetidine 800 mg BID are indicated for endoscopically diagnosed erosive esophagitis. This 12-week, randomized, multicenter trial involving 696 patients compared ranitidine 150 mg BID and ranitidine 150 mg QID with cimetidine 800 mg BID in healing erosive esophagitis. Healing rates, as determined by endoscopy, at 4, 8, and 12 weeks were comparable with ranitidine 150 mg BID (38%, 56%, and 71%, respectively) and cimetidine 800 mg BID (37%, 52%, and 68%, respectively), as were reductions in heartburn frequency and antacid consumption. However, ranitidine 150 mg QID produced significantly higher healing rates (49%, 67%, and 77%, respectively) and greater reductions in heartburn frequency and antacid consumption than cimetidine 800 mg BID. All treatment regimens were well tolerated. Thus ranitidine 150 mg BID is as effective as cimetidine 800 mg BID, and ranitidine 150 mg QID is more effective than cimetidine 800 mg BID in healing erosive esophagitis and reducing heartburn frequency and antacid consumption.

Reliability and changes in validity of self-reported cardiovascular disease risk factors using dual response: the behavioral risk factor survey.

The authors previously studied the validity of self-reported cardiovascular disease (CVD) risk factors assessed by telephone surveys, and found the validity low, especially for self-reported hypertension and hypercholesterolemia. One way to improve validity is to combine repeated measurements (dual response) into a single measure. The authors explored this and the reliability of self-reported CVD data collected by the Behavioral Risk Factor Survey in three New York counties from January 1989 to May 1990. Nine hundred and eleven subjects were interviewed by telephone to collect CVD risk factor and health behavior information. Interviewees were offered physical examination and laboratory testing to verify self-reported CVD risk factors; 628 participated. Subjects were also reinterviewed to assess the test-retest reliability of the survey, and to study how validity of self-reported CVD data changes by dual response. Reliability coefficients for CVD risk factors, preventive health practices, and knowledge of risk factor levels ranged from 0.42 to 0.99. Minimal improvement in sensitivity of self-reported risk factors was found using dual response, and it did not improve specificity. Also, for prevalence of risk factors, dual response minimally improved self-reported rates compared to objective estimates. Combining self-reported measurements causes minimal changes in the validity of these variables. Physiological assessment for hypertension and hypercholesterolemia, or correction for misclassification, is needed for valid individual measurement and for community prevalence estimates from telephone surveys. Self-reported cigarette smoking, obesity, and diabetes mellitus have better validity, but physiological assessment or correction for misclassification may supplement these self-reported risk factors.

Validity of cardiovascular disease risk factors assessed by telephone survey: the Behavioral Risk Factor Survey.

The Behavioral Risk Factor Surveillance System (BRFSS) collects telephone interview data on behaviors for the leading causes of premature death and disability. Its validity has never been adequately studied. The authors replicated BRFSS methodology to validate self-reported cardiovascular disease (CVD) risk factors. Nine-hundred and eleven subjects from three upstate New York counties were interviewed between 1/89 and 5/90. Interviewees were offered physical examinations and laboratory testing for CVD risk factors; 282 men and 344 women participated. The authors studied validity by comparing objectively measured to self-reported CVD risk factors. Sensitivities for self-reported hypertension, hypercholesterolemia, obesity, smoking, and diabetes were: 43, 44, 74, 82 and 75%, respectively. Only smoking sensitivity differed by gender: men, 77%; women, 86%. Specificity was > 85% for all risk factors, except hypercholesterolemia in men (75%). Prevalence was underreported for hypertension, hypercholesterolemia, obesity, and smoking by 43, 50, 25 and 17%, respectively. Results suggest telephone survey research includes physiologic measurements for blood pressure, cholesterol, height, weight, and smoking to validate self-reported CVD risk factors. When this is impossible, results such as these can be used, in similar samples, to correct risk factor prevalence rates from telephone surveys for misclassifications.