Assessment of Frailty and Association With Progression of Benign Prostatic Hyperplasia Symptoms and Serious Adverse Events Among Men Using Drug Therapy.

Importance: Benign prostatic hyperplasia (BPH) in older men can cause lower urinary tract symptoms (LUTS), which are increasingly managed with medications. Frailty may contribute to both symptom progression and serious adverse events (SAEs), shifting the balance of benefits and harms of drug therapy. Objective: To assess the association between a deficit accumulation frailty index and clinical BPH progression or SAE. Design, Setting, and Participants: This cohort study used data from the Medical Therapy of Prostatic Symptoms trial, which compared placebo, doxazosin, finasteride, and combination therapy in men with moderate-to-severe LUTS, reduced urinary flow rate, and no prior BPH interventions, hypotension, or elevated prostate-specific antigen. Enrollment was from 1995 to 1998, and follow-up was through 2001. Data were assessed in February 2021. Exposures: A frailty index (score range, 0-1) using 68 potential deficits collected at baseline was used to categorized men as robust (score ≤0.1), prefrail (score 0.1 to <0.25), or frail (score ≥0.25). Main Outcomes and Measures: Primary outcomes were time to clinical BPH progression and time to SAE, as defined in the parent trial. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regressions adjusted for demographic variables, treatment group, measures of obstruction, and comorbidities. Results: Among 3047 men (mean [SD] age, 62.6 [7.3] years; range, 50-89 years) in this analysis, 745 (24%) were robust, 1824 (60%) were prefrail, and 478 (16%) were frail at baseline. Compared with robust men, frail men were older (age ≥75 years, 12 men [2%] vs 62 men [13%]), less likely to be White (646 men [87%] vs 344 men [72%]), less likely to be married (599 men [80%] vs 342 men [72%]), and less likely to have 16 years or more of education (471 men [63%] vs 150 men [31%]). During mean (SD) follow-up of 4.0 (1.5) years, the incidence rate of clinical BPH progression was 2.2 events per 100 person-years among robust men, 2.9 events per 100 person-years among prefrail men (AHR, 1.36; 95% CI, 1.02-1.83), and 4.0 events per 100 person-years among frail men (AHR, 1.82; 95% CI, 1.24-2.67; linear P = .005). Larger point estimates were seen among men who received doxazosin or combination therapy, although the test for interaction between frailty index and treatment group did not reach statistical significance (P for interaction = .06). Risk of SAE was higher among prefrail and frail men (prefrail vs robust AHR, 1.81; 95% CI, 1.48-2.23; frail vs robust AHR, 2.86; 95% CI, 2.21-3.69; linear P < .001); this association was similar across treatment groups (P for interaction = .76). Conclusions and Relevance: These findings suggest that frailty is independently associated with greater risk of both clinical BPH progression and SAEs. Older frail men with BPH considering initiation of drug therapy should be counseled regarding their higher risk of progression despite combination therapy and their likelihood of experiencing SAEs regardless of treatment choice.

The interrelation of endothelial function and microvascular reactivity in different vascular beds, and risk assessment in hypertension: results from the Doxazosin-ramipril study.

There are several non-invasive methods to study endothelial function, but their interrelation and association to cardiovascular risk have not been well evaluated. We studied macrovascular and microvascular endothelial function simultaneously in different vascular beds in relation to cardiovascular mortality risk (Systematic Coronary Risk Evaluation, SCORE) and hypertension induced cardiac organ damage, and their interrelationship. The study investigated 71 hypertensive patients by forearm post-ischemic flow-mediated vasodilation, pulse wave analysis (applanation tonometry) and beta 2-adrenoceptor agonist stimulation for changes in reflection index, skin microvascular reactivity by laser Doppler fluxmetry with iontophoresis and heat-induced hyperaemia, and coronary microvascular function by subendocardial viability ratio (derived from pulse wave analysis). Flow mediated vasodilation related inversely to SCORE (r = 0.34, P = 0.011). Adding microalbuminuria and pulse wave velocity strengthened the associations. Pulse wave reflection changes did not relate to SCORE. Skin microvascular reactivity related inversely to SCORE (peak flux change to sodium nitroprusside r = 0.29, P = 0.033, and to heating r = 0.31, P = 0.018). Subendocardial viability ratio did not relate to SCORE. Endothelial function indices showed no consistent relation to cardiac target organ damage. The agreement between the different methods for evaluating indices of macrovascular and microvascular endothelial function was weak. In conclusion, indices of macrovascular and microvascular endothelial function relate to cardiovascular mortality risk. Their use may improve cardiovascular risk prediction in hypertension. However, methods representing different vascular beds show little interrelationship and are not interchangeable, which may depend on different pathogenetic mechanisms representing different aspects of future cardiovascular risk.Trial registry: NCT02901977.

Cost-Effectiveness of Combination Therapy Versus Monotherapy in Benign Prostatic Hyperplasia: A Colombian Experience.

OBJECTIVES: To estimate the incremental cost-effectiveness ratio of pharmacological treatment for benign prostatic hyperplasia from the payer's perspective. METHODS: The cost-effectiveness of 5 mg finasteride, 0.5 mg dutasteride, 10 mg alfuzosin, 10 mg terazosin, 0.4 mg tamsulosin, 4 mg doxazosin, and the combination therapy of 5 mg finasteride and 8 mg doxazosin was evaluated using a Markov model over a 30-year period. The costs were estimated using national tariffs and were reported in US dollars. Cost and effectiveness outcomes were discounted at a rate of 5% per year. Men (aged ≥40 years) with moderate to severe lower urinary tract symptoms and uncomplicated benign prostatic hyperplasia were included in the analysis. Outcomes included costs and quality-adjusted life-years. A probabilistic sensitivity analysis was performed on important parameters with Monte-Carlo simulation. RESULTS: Finasteride alone or in combination with doxazosin dominated all α-blockers. After excluding dominated alternatives, the incremental cost-utility ratio for combination therapy was $377 per quality-adjusted life-year, being a cost-effective alternative using the threshold of $15 000. Model results were robust to changes in costs, utility weights, and probabilities. Acceptability curves consistently demonstrated that the combination therapy was most likely cost-effective. CONCLUSIONS: The combination of finasteride and doxazosin is cost-effective compared with dutasteride, tamsulosin, terazosin, and alfuzosin in patients with benign prostatic hyperplasia with moderate or severe symptoms who are older than 40 years.

Cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia in the Brazilian public health system.

OBJECTIVE: To perform a cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia (BPH) under Brazilian public health system perspective (Unified Health System--"Sistema Unico de Saude (SUS)"). MATERIAL AND METHODS: A revision of the literature of the medical treatment of BPH using alpha-blockers, 5-alpha-reductase inhibitors and combinations was carried out. A panel of specialists defined the use of public health resources during episodes of acute urinary retention (AUR), the treatment and the evolution of these patients in public hospitals. A model of economic analysis (Markov) predicted the number of episodes of AUR and surgeries (open prostatectomy and transurethral resection of the prostate) related to BPH according to stages of evolution of the disease. Brazilian currency was converted to American dollars according to the theory of Purchasing Power Parity (PPP 2010: US$ 1 = R$ 1.70). RESULTS: The use of finasteride reduced 59.6% of AUR episodes and 57.9% the need of surgery compared to placebo, in a period of six years and taking into account a treatment discontinuity rate of 34%. The mean cost of treatment was R$ 764.11 (US$ 449.78) and R$ 579.57 (US$ 340.92) per patient in the finasteride and placebo groups, respectively. The incremental cost-effectiveness ratio (ICERs) was R$ 4.130 (US$ 2.429) per episode of AUR avoided and R$ 2.735 (US$ 1.609) per episode of surgery avoided. The comparison of finasteride + doxazosine to placebo showed a reduction of 75.7% of AUR episodes and 66.8% of surgeries in a 4 year time horizon, with a ICERs of R$ 21.191 (US$ 12.918) per AUR episodes avoided and R$ 11.980 (US$ 7.047) per surgery avoided. In the sensitivity analysis the adhesion rate to treatment and the cost of finasteride were the main variables that influenced the results. CONCLUSIONS: These findings suggest that the treatment of BPH with finasteride is cost-effective compared to placebo in the Brazilian public health system perspective.

Cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia in the Brazilian public health system

OBJECTIVE: To perform a cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia (BPH) under Brazilian public health system perspective (Unified Health System - "Sistema Único de Saúde (SUS)"). MATERIAL AND METHODS: A revision of the literature of the medical treatment of BPH using alpha-blockers, 5-alpha-reductase inhibitors and combinations was carried out. A panel of specialists defined the use of public health resources during episodes of acute urinary retention (AUR), the treatment and the evolution of these patients in public hospitals. A model of economic analysis(Markov) predicted the number of episodes of AUR and surgeries (open prostatectomy and transurethral resection of the prostate) related to BPH according to stages of evolution of the disease. Brazilian currency was converted to American dollars according to the theory of Purchasing Power Parity (PPP 2010: US$ 1 = R$ 1.70). RESULTS: The use of finasteride reduced 59.6% of AUR episodes and 57.9% the need of surgery compared to placebo, in a period of six years and taking into account a treatment discontinuity rate of 34%. The mean cost of treatment was R$ 764.11 (US$449.78) and R$ 579.57 (US$ 340.92) per patient in the finasteride and placebo groups, respectively. The incremental cost-effectiveness ratio (ICERs) was R$ 4.130 (US$ 2.429) per episode of AUR avoided and R$ 2.735 (US$ 1.609) per episode of surgery avoided. The comparison of finasteride + doxazosine to placebo showed a reduction of 75.7% of AUR episodes and 66.8% of surgeries in a 4 year time horizon, with a ICERs of R$ 21.191 (US$ 12.918) per AUR episodes avoided and R$ 11.980 (US$ 7.047) per surgery avoided. In the sensitivity analysis the adhesion rate to treatment and the cost of finasteride were the main variables that influenced the results. CONCLUSIONS: These findings suggest that the treatment of BPH with finasteride is cost-effective compared to placebo in the Brazilian public health system perspective.

Orthostatic hypertension: home blood pressure monitoring for detection and assessment of treatment with doxazosin.

To determine the role of home blood pressure (BP) monitoring for a reproducible assessment of orthostatic hypertension (OHT) and the effectiveness of hypertension control by doxazosin. In this study, 605 medicated hypertensive outpatients were enrolled. Home BP in the sitting and standing positions was monitored in all patients in the morning and evening for 6 months. According to an open-label multicenter trial design, the patients were randomly allocated to either an intervention group that took doxazosin (1-4 mg) at bedtime or to a control group that did not receive any add-on medication. The patients were divided into deciles of orthostatic BP change as evaluated by home BP monitoring at baseline. Those in the top decile, in the lowest decile and in deciles two through eight were then assigned to the OHT group, the orthostatic hypotension group and the orthostatic normotension group, respectively.Orthostatic BP in the OHYPO group did not change, whereas that of the OHT group was markedly reduced by doxazosin (P<0.01). In the control group, classification into orthostatic BP categories using home BP monitoring was more reproducible (κ coefficient: 0.42-0.50) than when using clinical BP (κ coefficient: 0.13-0.24). In all groups, a reduction in the urinary albumin/creatinine ratio was significantly associated with a reduction in orthostatic BP doxazosin (P<0.001).The identification of OHT based on home BP monitoring was highly reproducible. The administration of doxazosin might control OHT and consequently prevent target organ damage.

[Population analysis by area of health of changes in consumption, price and expenditure of cardiovascular drugs in eight autonomous communities, Spain, 2005]. / Análisis poblacional por áreas de salud de las variaciones en consumo, precio y gasto de medicamentos cardiovasculares en 8 comunidades autónomas, españa, 2005.

BACKGROUND: Variability in cardiovascular drugs is of great interest because of its high population use, its high expenditure and the availability of strong evidence supporting its use. The aim of this study is to describe variation in dispensation, price and pharmaceutical expenditure for 11 subgroups of cardiovascular drugs by healthcare areas. METHODS: This was a population study describing dispensation for 11 subgroups of cardiovascular drugs among healthcare areas in 2005. POPULATION: 93 healthcare areas of the 8 participant Autonomous Regions. ANALYSIS: Descriptive analysis of dispensation (Defined Daily Dose (DDD) per 1,000 pensioners and day (DDD/1000P/Day), average price (euros per DDD), pharmaceutical expenditure (euros per 100 pensioners) and standardized consumption ratios. Small-area variation analysis was used to analyze observed variability. RESULTS: Consumption of cardiovascular drugs oscillated between 324 DDD/1000p/Day for drugs with action on the renin-angiotensin system, and 6.5 DDD/1000p/Day for anti-aldosterone diuretics. Variation in consumption for areas in the 5th and 95th percentiles went from 1.8 times (digitalics) to 17.2 times (flavonoids), although most of the groups showed an extremal quotient of around 5. Variation in average prices was lower than in consumption (1.1 times for doxazosin and 3.7 for flavonoids) and variations in pharmaceutical expenditure was similar to variation in consumption (from 2.0 timesfor digitalics to 13.0 times for flavonoids). CONCLUSIONS: Major variations in the consumption of cardiovascular drugs between healthcare areas, together with discreet variations in price mean there are big differences in pharmaceutical expenditure from one population to another.

Finasteride for benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH), a non-malignant enlargement of the prostate in aging men, can cause bothersome urinary symptoms (intermittency, weak stream, straining, urgency, frequency, incomplete emptying). Finasteride, a five-alpha reductase inhibitor (5ARI), blocks the conversion of testosterone to dihydrotestosterone, reduces prostate size, and is commonly used to treat symptoms associated with BPH. OBJECTIVES: To compare the clinical effectiveness and harms of finasteride versus placebo and active controls in the treatment of lower urinary tract symptoms (LUTS). SEARCH STRATEGY: We searched The Cochrane Library (which includes CDSR (Cochrane Database of Systematic Reviews), DARE (Database of Abstracts of Reviews of Effects), HTA (Heath Technology Assessments), and CENTRAL (Cochrane Central Register of Controlled Trials, and which includes EMBASE and MEDLINE), LILACS (Latin American and Caribbean Center on Health Sciences Information) and Google Scholar for randomized, controlled trials (RCTs). We also handsearched systematic reviews, references, and clinical-practice guidelines. SELECTION CRITERIA: Randomized trials in the English language with placebo and/or active arms with a duration of at least 6 months. DATA COLLECTION AND ANALYSIS: JT extracted the data, which included patient characteristics, outcomes, and harms. Our primary outcome was change in a validated, urinary symptom-scale score, such as the AUA/IPSS. A clinically meaningful change was defined as 4 points. We also categorized outcomes by trial lengths of ≤ 1 year (short term) and > 1 year (long term). MAIN RESULTS: Finasteride consistently improved urinary symptom scores more than placebo in trials of > 1 year duration, and significantly lowered the risk of BPH progression (acute urinary retention, risk of surgical intervention, ≥ 4 point increase in the AUASI/IPSS). In comparison to alpha-blocker monotherapy, finasteride was less effective than either doxazosin or terazosin, but equally effective compared to tamsulosin. Both doxazosin and terazosin were significantly more likely than finasteride to improve peak urine flow and nocturia, versus finasteride. Versus tamsulosin, peak urine flow and QoL improved equally well versus finasteride. However, finasteride was associated with a lower risk of surgical intervention compared to doxazosin, but not to terazosin, while finasteride and doxazosin were no different for risk of acute urinary retention. Two small trials reported no difference in urinary symptom scores between finasteride and tamsulosin. Finasteride + doxazosin and doxazosin monotherapy improved urinary symptoms equally well (≥ 4 point improvement).For finasteride, there was an increased risk of ejaculation disorder, impotence, and lowered libido, versus placebo. Versus doxazosin, finasteride had a lower risk of asthenia, dizziness, and postural hypotension, and versus terazosin, finasteride had a significant, lower risk of asthenia, dizziness, and postural hypotension. AUTHORS' CONCLUSIONS: Finasteride improves long-term urinary symptoms versus placebo, but is less effective than doxazosin. Long-term combination therapy with alpha blockers (doxazosin, terazosin) improves symptoms significantly better than finasteride monotherapy. Finasteride + doxazosin improves symptoms equally - and clinically - to doxazosin alone. In comparison to doxazosin, finasteride + doxazosin appears to improve urinary symptoms only in men with medium (25 to < 40 mL) or large prostates (≥ 40 mL), but not in men with small prostates (25 mL).Comparing short to long-term therapy, finasteride does not improve symptoms significantly better than placebo at the short term, but in the long term it does, although the magnitude of differences was very small (from < 1.0 point to 2.2 points). Doxazosin improves symptoms better than finasteride both short and long term, with the magnitude of differences ∼2.0 points and 1.0 point, respectively. Finasteride + doxazosin improves scores versus finasteride alone at both short and long term, with mean differences ∼2.0 points for both time points. Finasteride + doxazosin versus doxazosin improves scores equally for short and long term.Drug-related adverse effects for finasteride are rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo. Versus doxazosin, which has higher rates of dizziness, postural hypotension, and asthenia, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder. Finasteride significantly reduces asthenia, postural hypotension, and dizziness versus terazosin. Finasteride significantly lowers the risk of asthenia, dizziness, ejaculation disorder, and postural hypotension, versus finasteride + terazosin.

Assessment of therapeutic drug efficiency.

The efficiency of drug therapy should be evaluated by not only its directed action on specific organ or target parameter, but also its effects on general regulatory and adaptive status.

Assessment of alpha1-adrenoceptor antagonists in benign prostatic hyperplasia based on the receptor occupancy theory.

AIMS: To assess the mechanistic relationship between doxazosin (alpha(1)-receptor antagonist) and receptor occupancy and a measure of pharmacological effect (Q(max), the maximum urinary flow rate) and to compare the mean receptor occupancy ratio at clinical doses of doxazosin, tamsulosin, terazosin and prazosin in benign prostatic hyperplasia (BPH). METHODS: A ternary complex model, which described the mechanism of alpha(1)-receptor antagonists, was fitted to the pharmacological effects and receptor occupancy ratio data for doxazosin (standard tablet). In addition, mean receptor occupancy was calculated for other alpha(1)-receptor antagonists and the optimal receptor occupancy was evaluated. The clinical pharmacological effects of the controlled release formulation of doxazosin (doxazosin GITS) were estimated based on the receptor occupancy. RESULTS: The mechanistic based model was able to describe the pharmacological effects of doxazosin. Regardless of the plasma concentrations or clinical dose of each drug, the results suggest that receptor occupancy is useful to assess quantitatively and compare the pharmacological effects of drugs with similar mechanisms of action. The clinical dosage for doxazosin GITS was estimated to be at least 8 mg and the stable pharmacological effect is expected based on the estimated receptor occupancy. CONCLUSIONS: A model for Q(max) improvement in BPH based on the receptor occupancy theory was able to describe the clinical effects of the alpha(1)-receptor antagonists. Receptor occupancy is a useful index for predicting the clinical effects of alpha(1)-receptor antagonists.

Assessment of cognitive function in patients with essential hypertension treated with lercanidipine.

OBJECTIVES: The aim of this longitudinal, open-label, comparative, multicenter study was to assess cognitive function in hypertensive patients receiving mid-term treatment with lercanidipine. METHODS: Hypertensive patients aged 40 years or older were treated with lercanidipine (10 mg daily) after 7-10 days washout period. The duration of the study was 6 months. Blood pressure (BP) was measured every 4 weeks (JNC 6th report). In patients with inadequate BP control, doxazosin was added and up-titrated. At baseline and after 6 months of treatment, cognitive function was evaluated using the Spanish validated version of the Mini-Mental State Examination (MMSE) and the Trail Making Test (TMT). RESULTS: In the study population of 467 patients, BP decreased from 154.4/95.3 mmHg at baseline to 134.8/80.7 mmHg at 6 months. At the end of the study, 98% of patients were receiving lercanidipine, 20% an angiotensin-converting enzyme inhibitor, and 6% doxazosin. Adequate BP control was obtained in 68% of patients. The mean (standard deviation) MMSE scores improved from 32.35 (2.59) to 33.25 (2.36) (p < 0.0001). Patients with good BP control scored significantly better than those with inadequate BP control (p < 0.05), which was already observed at the first month. CONCLUSIONS: The third-generation calcium channel antagonist, lercanidipine, improved cognitive function after 6 months of treatment especially in patients with good BP control, suggesting that improvements in cognitive function may be associated with a decrease in BP.

An economic evaluation of doxazosin, finasteride and combination therapy in the treatment of benign prostatic hyperplasia.

OBJECTIVE: The Proscar Long-Term Efficacy and Safety Study (PLESS) and the Medical Therapy of Prostatic Symptoms (MTOPS) study provide new evidence regarding the benefits of finasteride in the treatment of benign prostatic hyperplasia (BPH). The objective of this study was to utilize data from the PLESS and MTOPS studies to assess the cost-utility of finasteride and finasteride in combination with doxazosin, compared to doxazosin alone in men with moderate to severe BPH symptoms. METHODS: A semi-Markov decision analytic model was constructed to estimate the clinical consequences, costs and cost-utility of doxazosin, finasteride, and combination therapy. Analyses were conducted for a 15-year time frame from the perspective of the Ontario Ministry of Health and Long Term Care (MOHLTC). Results are reported stratified by baseline serum prostate-specific antigen (PSA) level according to all baseline serum PSA levels, patients with baseline serum PSA > 1.3 ng/ml, and patients with baseline serum PSA > 3.2 ng/ml. RESULTS: Compared to doxazosin alone, combination therapy was more expensive but more effective. Cost-utility ratios ranged from 27,823 dollars/QALY for patients with PSA > 3.2 ng/ml to 34,085 dollars/QALY for all patients. Finasteride, although dominated by doxazosin, may be cost-effective compared to watchful waiting in patients who fail doxazosin and do not choose to proceed to surgery. Compared to watchful waiting, cost-utility ratios for finasteride ranged from 35016 dollars/QALY for patients with PSA > 3.2 ng/ml to 44,336 dollars/QALY for all patients. Results were robust across a wide range of sensitivity analyses. CONCLUSIONS: Combination therapy is cost-effective compared to doxazosin with cost-utility ratios under 40,000 dollars/QALY across a wide range of scenarios. The cost-effectiveness of combination therapy increases as serum PSA level increases.

Cost-effectiveness of tamsulosin, doxazosin, and terazosin in the treatment of benign prostatic hyperplasia.

OBJECTIVE: To evaluate the cost-effectiveness of tamsulosin, doxazosin, or terazosin as initial treatments for moderate benign prostatic hyperplasia (BPH) over a 3-year time horizon from a health-system-payer perspective. METHODS: A decision-analytic model is used to project the course of treatment at 6-month intervals over 3 years following initiation of therapy with tamsulosin, doxazosin, or terazosin. Treatment failure is defined as failure to attain and maintain a 25% improvement in the American Urological Association (AUA) symptom score from baseline. In the model, finasteride is added for patients who fail on their initial therapy and, in the event of finasteride treatment failure, patients progress to transurethral resection of the prostate (TURP) and, if needed, a second TURP. The ranges of values for treatment failure rates and clinical event cost parameters used in the decision model are derived from the literature. Only direct medical costs related to BPH and its treatment are included. Since 2 comparators are available generically (doxazosin and terazosin) drug acquisition costs are defined by the list prices at Drugstore.com. All costs are discounted by 3% per year. Effectiveness is measured as successful medical treatment without surgery over 3 years. RESULTS: For base-case model parameters, discounted BPH-related total direct medical costs over 3 years are 4084 dollars, 4323 dollars, and 4695 dollars for generic terazosin, generic doxazosin, and tamsulosin, respectively. The model estimates a medical treatment success rate (no TURP) at 3 years of 72.3% for tamsulosin, compared with 68.2% for both terazosin and doxazosin. The incremental cost for tamsulosin versus terazosin is 610 dollars over 3 years, which yields an incremental cost-effectiveness ratio of 14,609 dollars per success. Generic doxazosin is dominated (higher cost but equal effectiveness compared with terazosin). Higher rates of twice-daily (or 2 units per day) dosing are associated with higher incremental cost-effectiveness ratios. The decision-model results also are sensitive to the estimated costs of TURP and hypotensive adverse events. CONCLUSION: As an initial medical therapy for moderate BPH, tamsulosin is more effective than generic terazosin or doxazosin, with an incremental cost of about 203 dollars per year (or about 17 dollars per month) over 3 years.

Impact of clinical trial results on national trends in alpha-blocker prescribing, 1996-2002.

CONTEXT: Research on factors that influence prescribing patterns and the extent of change produced by clinical trial findings is limited. OBJECTIVE: To examine the changes in prescribing of alpha-blockers for hypertension treatment before and after the April 2000 publication of the unfavorable Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) early termination involving the study's doxazosin mesylate arm. Changes in prescribing were considered in the context of other potential concurrent influences on medication use between 1996 and 2002, including changes in alpha-blocker drug prices, generic conversion, drug promotion, and competition. DESIGN, SETTING, AND PATIENTS: Using 2 national pharmaceutical market research reports published by IMS HEALTH, alpha-blocker prescription orders reported in the National Prescription Audit-a random computerized sample of about 20 000 of 29 000 retail, independent, and mail order pharmacies and mass merchandise and discount houses--and office-based physician alpha-blocker prescribing patterns reported in the National Disease and Therapeutic Index--a random stratified sample of about 3500 physician offices--were tracked. OUTCOME MEASURES: Trends in physician-reported use of alpha-blockers and alpha-blocker prescribing and dispensing by US pharmacies. RESULTS: There were steady increases in alpha-blocker new prescriptions, dispensed prescriptions, and physician drug use from 1996 through 1999. There was a moderate reversal in these trends following ALLHAT early termination and subsequent publications in early 2000. Between 1999 and 2002, new annual alpha-blocker prescription orders declined by 26% (from 5.15 million to 3.79 million), dispensed prescriptions by 22% (from 17.2 million to 13.4 million), and physician-reported drug use by 54% (from 2.26 million to 1.03 million). Other potential influences did not appear to have contributed significantly to this decline although cessation of alpha-blocker marketing may have hastened the decline. CONCLUSIONS: Modest yet statistically significant declines in the use of doxazosin and other alpha-blockers coincided with the early termination of the ALLHAT doxazosin arm. Although physicians responded to this new evidence, strategies to augment the impact of clinical trials on clinical practice are warranted.

Lower urinary tract symptoms, pain and quality of life assessment in chronic non-bacterial prostatitis patients treated with alpha-blocking agent doxazosin; versus placebo.

The efficacy of doxazosin monotherapy in chronic non-bacterial prostatitis was investigated in terms of urinary symptom, pain and quality of life assessment versus placebo. A total of 60 men with chronic non-bacterial prostatitis were randomised to daily supplement of 4 mg doxazosin or a placebo, for 3 months. International Prostate Symptom Score (IPSS) questionnaire was self administered at the entry and at 3 months after the cessation of the treatment. In addition, patients were asked to complete 2-item questionnaire on pain related symptoms of chronic prostatitis. Quality of life was assessed with a single item included in IPSS. Three months after cessation of the treatment there was a significant difference between the overall mean IPSS, pain and quality of life scores of the two groups in favour of alpha-blocking agent use (p = 0.001, p < 0.001 and p < 0.001, respectively). In patients undergone doxazosin treatment; symptom, pain and quality of life status revealed 32.94 +/- 5.27%, 36.57 +/- 5.67% and 36.78 +/- 4.75% overall improvement, respectively. IPSS appeared to be a valuable tool in assessing treatment outcome of chronic non-bacterial prostatitis.

Quality-of-life assessment in patients with benign prostatic hyperplasia: effects of various interventions.

A literature search was conducted to review quality-of-life (QOL) measurement in patients with benign prostatic hypertrophy (BPH). The different QOL instruments are discussed in relation to their correlation with symptom evaluation in studies of treatment options for BPH. Symptom evaluation of BPH has been standardised internationally with the International Prostatic Symptom Score (IPSS), but there is neither agreement nor data to decide which QOL instrument is preferable. The most widely used QOL instrument is the disease-specific QOL single question added to the IPSS. Other QOL instruments have been used, but none has gained unanimous approval. The results of QOL assessments obtained from comparative clinical studies of treatment options for BPH are discussed. These studies compare treatment options such as watchful waiting, drug treatment and surgery. Disease-specific QOL domains (interference with daily activities) tend to improve more with treatment interventions than general health measures (i.e. general well-being). The use of QOL instruments to evaluate patients with BPH, and their many treatment options, is still open to debate with regard to which instruments are preferred and their importance to the clinical evaluation of the patient. The challenge remains to find an acceptable disease-specific QOL instrument that adds information to currently used disease measures of BPH.

The cost-effectiveness of doxazosin for the treatment of hypertension in type II diabetic patients in the UK and Italy.

The objective of this analysis was to assess the cost-effectiveness of achieving 'tight control' versus 'less tight control' of blood pressure, as defined in the UK Prospective Diabetics Study 38, in type II diabetic patients in the UK and Italy. The effect of including doxazosin in a 'tight control' combination therapy was analysed. Given doxazosin's positive impact on lipid levels in addition to its antihypertensive effect, it is hypothesised that treatment including doxazosin will reduce the incidence of macrovascular complications. For each country, a Markov model was constructed to simulate macrovascular outcomes of patients on various drug combinations. Transitional probabilities were based on the risk rates presented in UKPDS 38. Risk rates were adjusted for the ageing of the cohort and the lipid-lowering properties of doxazosin using Framingham risk equations. Incremental cost-effectiveness ratios ranged from 2224 Pounds to 4867 Pounds (US$3225-7057) per life-year saved for the UK and from L1.8-9.3 million (US$818-4159) per life-year saved for Italy. Doxazosin is a cost-effective agent when included in a combination therapy in the treatment of hypertension in the diabetic populations of the UK and Italy.

Effects of doxazosin in men with benign prostatic hyperplasia: urodynamic assessment.

OBJECTIVE: In this study, a randomized and placebo controlled trial, we aimed to study the effectiveness and safety of doxazosin based upon urodynamic parameters, especially pressure/flow studies, in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 57 men (29 doxazosin, 28 placebo) 48-82 years of age with BPH were enrolled. Yet, 8 of 29 in the doxazosin group and 10 of 28 in the placebo group were excluded due to side effects of doxazosin and intolerability of urodynamic assessment of free uroflow, postvoiding residual urine volume (PVR) and pressure/flow studies. RESULTS: There were improvements in all urodynamic parameters (Free Qmax: 30.4% and 28%, PVR: 14 ml and 12 ml, invasive Qmax: 29.3% and 26.2%, Pdet at Qmax: -32.7% and -30%, Pdet-max: -29% and -27.7% at end of the 1st and 6th months whereas placebo effects were worsening in all urodynamic parameters. CONCLUSIONS: We suggest that doxazosin is an important treatment option for patients with BPH, and efficacy of doxazosin should be evaluated with objective, quantitative urodynamic studies not with subjective symptom scores. But additional costs and invasiveness of urodynamic studies restrict their common usefulness.