托特罗定治疗特发性膀胱过度活动症

目的观察新型毒蕈咸受体拮抗药托特罗定治疗特发性膀胱过度活动症的有效性和安全性。方法将托特罗定1mg呼奥昔布宁5mg及安慰剂进行对比,疗程3周。夜间入睡前2h口服。结果与安慰剂相比,托特罗定和奥昔布宁都使入睡前1h夜尿次数(P<0.01)显著减少。两种药物的副作用主要为口干。在口干(发生率和强度)方面,托特罗定要明显优于奥昔布宁(P<0.05)。结论托特罗定治疗特发性膀胱过度活动症效果明确,疗程3周即能达到疗效。尽管奥昔布宁也具有很好的疗效,但不良反应限制了它的应用。     

Tolterodine use for symptoms of overactive bladder.

OBJECTIVE: To describe the pharmacology, pharmacokinetics, clinical efficacy, and safety of tolterodine for the treatment of overactive bladder. DATA SOURCES: Published articles and abstracts were identified from a MEDLINE search (January 1980-October 1998) using the terms tolterodine, PNU-200583E, urge incontinence, overactive bladder, detrusor instability, detrusor overactivity, and antimuscarinic. Pertinent articles written in English were considered for review. Additional articles were identified from the bibliographies of retrieved articles. Data from the Food and Drug Administration-approved product labeling and the manufacturer were also used in the absence of published data. STUDY SELECTION AND DATA EXTRACTION: Clinical studies of tolterodine involving human subjects were evaluated. DATA SYNTHESIS: Tolterodine is a competitive muscarinic receptor antagonist with relative functional selectivity for bladder muscarinic receptors. It is metabolized in the liver by CYP2D6 to an active metabolite (DD 01), which is partially responsible for its pharmacologic activity. Those who are genetically devoid of CYP2D6 will have higher concentrations of the parent compound and virtually undetectable concentrations of DD 01; however, the clinical efficacy does not appear to be altered. In dosages of 2 mg twice daily, tolterodine has shown consistent reductions in the number of micturitions per 24 hours and less consistently decreased incontinence episodes in patients with detrusor overactivity. The functional selectivity of tolterodine for bladder muscarinic receptors results in fewer systemic adverse effects, such as dry mouth, than occur with comparable nonselective antimuscarinic agents. CONCLUSIONS: Clinical studies have shown that the effectiveness of tolterodine for symptoms of overactive bladder is similar to that of oxybutynin. The adverse effect profiles of tolterodine and oxybutynin are similar; however, comparative clinical trials have shown significantly fewer patients taking tolterodine require dosage reductions or discontinue therapy due to antimuscarinic adverse effects such as dry mouth. Although more costly than oxybutynin, tolterodine represents a modest improvement over oxybutynin with respect to adverse effect profile, which may allow more patients with incontinence to tolerate therapeutic doses. Further research is necessary to determine whether tolterodine has clinical advantages over similar agents in patients with other muscarinic adverse effects, such as constipation or cognitive impairment.     

Comparisons of the therapeutic safety of seven oral antimuscarinic drugs in patients with overactive bladder: a network meta-analysis

ObjectivesThis network meta-analysis aimed to assess the safety profiles of seven commonly used oral antimuscarinic drugs (darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, and tolterodine) in patients with overactive bladder (OAB).MethodsPubMed, Cochrane Library, EMBASE, CNKI, and Wanfang databases were searched for randomized controlled trials (RCTs). Studies comparing one or more antimuscarinic drugs for treating OAB with reported adverse effects (AEs) were eligible. Data were extracted, and a network meta-analysis was performed by two authors independently.ResultsForty-five RCTs and 124,587 patients were included. The results demonstrated that tolterodine had better safety outcomes for 7 out of 12 major AEs, including dry mouth, constipation, urinary retention, dizziness, urinary tract infection, dry eyes, and dry skin. Darifenacin, fesoterodine, imidafenacin, oxybutynin, and solifenacin presented comparable safety profiles.ConclusionsTolterodine may be preferable as it showed a reduced association with important AEs. Darifenacin, fesoterodine, imidafenacin, oxybutynin, and solifenacin have similar safety profiles in treating patients with OAB. Taken together, this analysis provides a valuable overview of the therapeutic safety for oral antimuscarinic drugs and is useful for personalized medicine in patients with OAB.Trial registration: This trial was retrospectively registered at INPLASY (https://inplasy.com/) with the registration number 202170095.     

Canadian economic comparison of extended-release oxybutynin and immediate-release tolterodine in the treatment of overactive bladder

BACKGROUND: Overactive bladder (OAB) is a condition characterized by urgency, increased frequency of micturition, or urge incontinence. It affects a considerable segment of the population, particularly with increasing age. Pharmacotherapy is one of the most common approaches to the treatment of OAB. OBJECTIVE: This article describes the development and results of a model comparing health-economic outcomes for the new extended-release (XL) formulation of oxybutynin and immediate-release (IR) tolterodine in a population of community-dwelling Canadian adults with OAB. METHODS: A Markov model was developed to compare health-economic outcomes over the course of 1 year. Effectiveness and treatment-persistence data were derived from the OBJECT (Overactive Bladder: Judging Effective Control and Treatment) trial, a 3-month comparison of oxybutynin XL 10 mg and tolterodine IR 4 mg, and were used, together with data from the literature (identified through a MEDLINE search of articles published between 1990 and 2003), to project outcomes beyond the trial period. Severity-specific cost profiles for incontinence were developed. In the principal analyses, cost items were limited to drug therapy, physician visits, use of pads or other protection, and laundry costs. Costs are reported in 2002 Canadian dollars. RESULTS: Costs after 1 year were estimated to be an average of $32 less per patient for oxybutynin XL compared with tolterodine IR, and 3.1 additional patients in every 100 who received oxybutynin XL were expected to attain complete continence compared with those who received tolterodine. During the course of 1 year, patients receiving oxybutynin XL were expected to have a mean 16.5 additional incontinence-free days compared with those receiving tolterodine IR. The results were sensitive to relative drug prices. In the other sensitivity analyses, however, oxybutyrin XL maintained its advantage over a wide range of inputs. CONCLUSION: The results of these analyses suggest that when priced equivalently, oxybutynin XL would reduce costs and provide better results than tolterodine IR over 1 year of treatment.     

Influence of socioeconomic status on drug selection for the elderly in Canada

OBJECTIVE: To examine the association between socioeconomic status, as indicated by neighborhood median income levels, and physician drug selection between older, less expensive generic drugs and newer, more expensive brand-name drugs for elderly patients initiating drug therapy in a universal healthcare system. METHODS: We conducted a population-based, retrospective, cross-sectional study. Using healthcare administrative databases, we assessed the medication profiles of 128 314 patients from more than 1.4 million residents of Ontario > or =65 years old initiating antipsychotic, hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin), or ocular beta-blocker drug therapy from January 1, 1998, through December 31, 1999. We examined the selection of older generic drugs relative to newer brand-name agents for patients in each of 5 income quintiles. RESULTS: Overall, brand-name drug prescribing modestly increased with increasing income quintile after adjusting for patient age and gender (61.2% in the lowest income quintile vs. 64.1% in the highest income quintile; p value for trend < 0.001). Significant risk ratios comparing the highest with the lowest income-quintile patients were observed for selection of newer, brand-name antipsychotics (RR 1.14; 95% CI 1.06 to 1.23), older generic statins (RR 0.86; 95% CI 0.77 to 0.95), and newer, brand-name ocular beta-blockers (RR 1.13; 95% CI 1.02 to 1.25). CONCLUSIONS: This study suggests that income-related differences in treatment selection by physicians may exist. The reasons for these differences and subsequent impact on health outcomes warrant further investigation.     

Impact of prescribing guidelines for inpatient anticoagulation

BACKGROUND: Anticoagulants are widely used and represent a class of drugs that are problem-prone and have a high potential for adverse patient outcomes. As such, these drugs may be amenable to the use of prescribing guidelines. However, relatively little has been published on the effect of such guidelines on clinical outcomes or costs of care. OBJECTIVE: To assess whether guidelines improve the appropriateness of prescribing, clinical outcomes, and costs associated with use of anticoagulants in a sample of community hospitals in the US. METHODS: A retrospective analysis was performed of data voluntarily collected by 15 hospitals before (July-September 2001) and after (March-May 2002) implementation of anticoagulant prescribing guidelines. Statistical analyses of both patient- and hospital-level variables were conducted. RESULTS: Implementation of the guidelines resulted in a significant increase in the proportion of anticoagulants that were prescribed appropriately (59.8% vs 86.9%; p < 0.001). The guidelines also resulted in a shift in the type of anticoagulants prescribed (decreased use of unfractionated heparin and increased use of low-molecular-weight heparins). There was suggestive evidence, although not statistically significant, that the guidelines resulted in fewer anticoagulant-associated adverse events (total bleeding RR 0.71) and lower costs (savings of $56.15 per patient per day). CONCLUSIONS: While limitations existed with the study design, sufficient benefits were identified to warrant hospitals to consider use of these or similar guidelines on a routine basis. Clearly, additional study in this area would be useful.     

Darifenacin treatment for overactive bladder in patients who expressed dissatisfaction with prior extended-release antimuscarinic therapy

Introduction and objective: Patient perception of overactive bladder (OAB) treatment outcomes can be a useful indicator of benefit and may help drive persistence on treatment, which is known to be poor in OAB. It remains unclear whether OAB patients dissatisfied with one antimuscarinic can achieve satisfaction with another and supporting data are limited. This study investigated patient‐reported outcomes and clinical parameters during darifenacin treatment in OAB patients who expressed dissatisfaction with prior extended‐release (ER) oxybutynin or tolterodine therapy (administered for ≥ 1 week within the past year). Methods: This open‐label study was conducted in darifenacin‐naïve OAB patients. Patients received 7.5 mg darifenacin once daily with the possibility of up‐titrating to 15 mg after 2 weeks, for up to 12 weeks. Efficacy parameters included the Patient’s Perception of Bladder Condition (PPBC), patient satisfaction with treatment, micturition frequency and number of urgency and urge urinary incontinence (UUI) episodes. Adverse events (AEs) were also recorded. Results: In total, 497 patients were treated (84.1% women). Darifenacin treatment resulted in statistically significant improvements in PPBC scores, micturition frequency, urgency and UUI episodes from baseline at 12 weeks. The improvements were similar for patients previously treated with oxybutynin ER or tolterodine ER. More than 85% of patients expressed satisfaction with darifenacin. As noted in other studies, the most common AEs were dry mouth and constipation, but these infrequently resulted in treatment discontinuation, which was low overall. Conclusions: In this study, PPBC score and OAB symptoms were significantly improved, and satisfaction was high during treatment with darifenacin (7.5/15 mg) in patients who were dissatisfied with the previous antimuscarinic treatment.     

Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study

OBJECTIVE: To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. SUBJECTS AND METHODS: The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. RESULTS: A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. CONCLUSIONS: Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.     

Prospective,randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial

OBJECTIVE: To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder. PATIENTS AND METHODS: The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated. RESULTS: Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events. CONCLUSIONS: Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.     

A 5‐year retrospective audit of prescribing by a critical care outreach team

UK prescribing legislation changes made in 2006 and 2012 enabled appropriately qualified nurses to prescribe any licensed medication, and all controlled drugs in schedule 2–5 of the Misuse of Drugs Regulations 2001, for any medical condition within their clinical competence. Critical Care Outreach nurses who are independent nurse prescribers are ideally placed to ensure that acutely ill patients receive treatment without delay. The perceived challenge was how Critical Care Outreach nurses would be able to safely prescribe for a diverse patient group. This study informs this developing area of nurse prescribing in critical care practice. The aims of the audit were to: identify which medications were prescribed; develop a critical care outreach formulary; identify the frequency, timing and number of prescribing decisions being made; identify if prescribing practice changed over the years and provide information for our continuing professional development. This article reports on data collected from a 5‐year retrospective audit; of prescribing activity undertaken by nine independent nurse prescribers working in a 24/7 Critical Care Outreach team of a 600‐bedded district general hospital in the UK. In total, 8216 medication items were prescribed, with an average of 2·6 prescribed per shift. The most commonly prescribed items were intravenous fluids and analgesia, which were mostly prescribed at night and weekends. The audit has shown that Critical Care Outreach nurse prescribing is feasible in a whole hospital patient population. The majority of prescribing occurred after 16:00 and at night. Further research would be beneficial, particularly looking at patient outcomes following reviews from prescribing critical care outreach nurses. The audit is one of the only long‐term studies that describes prescribing practice in Critical Care Outreach teams in the UK.     

Comparative analysis of the effects of antimuscarinic agents on bladder functions in both nonhuman primates and rodents

Both the physiological role of muscarinic receptors for bladder function and the therapeutic efficacy of antimuscarinic agents for overactive bladder syndrome are well documented. We investigated the effect of antimuscarinic agents with different subtype selectivity on urodynamic parameters in nonhuman primates and rodents and compared plasma levels of these agents between species. Anesthetized rhesus monkeys were transurethrally catheterized, and the bladder was infused with saline. Urodynamic parameters were measured before and after intravenous drug administration. Tolterodine (nonselective) and oxybutynin (moderately M(3)-selective) increased bladder capacity at lower doses than those required to decrease micturition pressure. However, higher doses of darifenacin (M(3)-selective) were needed to increase the bladder capacity than those needed to decrease the micturition pressure. In rats, tolterodine had no effect on the bladder capacity but decreased the micturition pressure at all of the doses administered. Oxybutynin also decreased micturition pressure and increased bladder capacity at the highest dose. Plasma levels of these drugs overlap in both species. These results suggest that, in addition to the M(3) receptor, other muscarinic receptor subtypes contribute to regulate bladder storage function in nonhuman primates, since less subtype-selective tolterodine and oxybutynin showed higher specificity to the bladder capacity effect than the effect on micturition pressure compared with M(3)-selective darifenacin. In addition, the role of muscarinic receptors in bladder storage function varies between primates and rodents. Compared with rodents, muscarinic receptors may play a more active role during the storage phase to regulate the functional bladder capacity in primates.     

A review of flavoxate hydrochloride in the treatment of urge incontinence

This article provides a review of the use of flavoxate hydrochloride in the treatment of urge incontinence. It outlines the pharmacology, mode of action, toxicology and pharmacokinetic studies which have been carried out, and then reviews the clinical studies, including those involving patients with benign prostatic hypertrophy. The effects of dosages of 600-1200 mg/day are compared, particularly regarding safety and tolerability factors. Finally, alternative therapies to flavoxate hydrochloride (alpha-adrenergic receptor blockers, oxybutinin chloride, terodiline hydrochloride, emepronium bromide and imipramine) are summarized. The article is written in the knowledge of recent evidence which indicates that flavoxate hydrochloride exhibits only weak anticholinergic activity on receptors involved in the control of the lower urinary tract.     

Practice patterns and perceptions about parenteral hydration in the last weeks of life: a survey of palliative care physicians in Latin America

ContextParenteral hydration at the end of life is controversial and has generated considerable debate for decades.ObjectivesTo identify palliative care physician parenteral hydration prescribing patterns and factors that influence prescribing levels (PLs) for patients during their last weeks of life.MethodsA cross-sectional, representative online survey of Latin American palliative care physicians was conducted in 2010. Physicians were asked to report the percentage of their terminally ill patients for whom they prescribed parenteral hydration. Predictors of parenteral hydration PLs were identified using logistic regression analysis.ResultsTwo hundred thirty-eight of 320 physicians completed the survey (74% response rate). Sixty percent of physicians reported prescribing parenteral hydration to 40%–100% of their patients during the last weeks of life. Factors influencing moderate/high PLs were the following: agreeing that parenteral hydration is clinically and psychologically efficacious (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.5–8.3), disagreeing that withholding parenteral hydration alleviates symptoms (OR 3.3, 95% CI 1.3–8.1), agreeing that parenteral hydration is essential for meeting the minimum standards of care (OR 3.2, 95% CI 1.4–7.5), preferring the subcutaneous route of parenteral hydration for patient comfort and home use (OR 2.9, 95% CI 1.3–6.5), and being younger than 45 years of age (OR 2.6, 95% CI 1.3–5.2).ConclusionThe strongest determinant of prescribing patterns was agreement with the clinical/psychological efficaciousness of parenteral hydration. Our results reflect parenteral hydration prescribing patterns and perceptions that substantially differ from the conventional/traditional hospice philosophy. These findings suggest that the decision to prescribe or withhold parenteral hydration is largely based on clinical perceptions and that most palliative care physicians from this region of the world individualize treatment decisions.     

Determinants of antidepressant medication prescribing in elderly residents of aged care homes in Australia: A retrospective study

Background: Depression is underrecognized and poorly treated among older people living in aged care homes worldwide. Depression has been associated with higher rates of recurrence, disability, and death in older people.Objectives: The primary objective of this study was to assess the determinants of antidepressant medication prescribing among older people living in aged care homes in Australia. A further objective was to investigate the anti-depressant medications in common use, doses of antidepressants, and concurrent pharmacotherapy among people receiving antidepressants.Methods: A random sample of 500 deidentified medication review reports was extracted from a database containing >165,000 Residential Medication Management Review reports. Residents' demographic and clinical characteristics, medical diagnoses, and prescribed medications were systematically extracted from these reports. Logistic regression models were used to determine factors associated with the prescribing of any antidepressant, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and “other” antidepressants (eg, mianserin, mirtazapine, venlafaxine).Results: The mean (SD) age of the residents was 84.0 (9.0) years. Seventy-five percent were female. The prevalence of antidepressant prescribing among these aged care home residents was 33.0%. SSRIs were more commonly prescribed than TCAs, monoamine oxidase inhibitors, and other antidepressants. Antidepressants were more likely to be prescribed in people treated for dementia with mood disorder (odds ratio [OR] = 9.70; 95% CI, 5.26–17.88), depression (OR = 13.28; 95% CI, 6.44–27.36), and Parkinson's disease (OR = 3.56; 95% CI, 1.37–9.23). SSRI prescribing was associated with dementia with mood disorder (OR = 5.85; 95% CI, 3.19–10.72) and depression (OR = 6.44; 95% CI, 3.38–12.26). TCA prescribing was associated with depression (OR = 2.95; 95% CI, 1.18–7.35) and concurrent benzodiazepine use (OR = 2.43; 95% CI, 1.03–5.72). Other antidepressant prescribing was associated with dementia with mood disorder (OR = 6.53; 95% CI, 3.15–13.50) and depression (OR = 5.00; 95% CI, 2.23–11.19).Conclusions: There was preferential prescribing of SSRI antidepressants among these older aged care home residents with depression. Cognitive impairment alone was not significantly associated with antidepressant prescribing; however, these aged care home residents with dementia and mood disorders had an increased likelihood of being treated with antidepressants. The prescribing of TCAs was significantly associated with concurrent benzodiazepine use.     

Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin

Background: Antimuscarinic agents used in the treatment of overactive bladder (OAB) differ in their potential to impair cognitive function. It is hypothesised that low brain concentrations and relatively low selectivity for the M₁ muscarinic receptor may reduce the potential for adverse central nervous system (CNS) effects with darifenacin, compared with other antimuscarinics, particularly oxybutynin. Methods: Cognitive function studies evaluating darifenacin, oxybutynin, tolterodine, solifenacin and/or trospium were identified from publications databases (Medline, Biosis and Embase) and congress abstracts. Preclinical studies and randomised controlled trials in adults were reviewed. Results: Five randomised, double‐blind, multiple‐dose studies of cognitive function were identified. Oxybutynin was consistently associated with cognitive deficit (four studies), whereas darifenacin did not impair cognition (three studies). These findings were supported by data from sleep/attention and EEG studies. Tolterodine data were limited to one small study with each formulation. For solifenacin and trospium, there were no human studies evaluating memory, the cognitive function most vulnerable to CNS anticholinergics. Conclusions: There is compelling evidence of cognitive impairment with oxybutynin, whereas darifenacin stands out by demonstrating no impairment of memory or other cognitive functions in three randomised, controlled trials. This may be attributed to the differences in physicochemical properties, efflux mechanisms and relative M₁ muscarinic receptor sparing. The risk of CNS impairment is of particular concern for vulnerable populations such as the elderly (a substantial proportion of the OAB population), and CNS‐compromised neurogenic bladder patients such as those with multiple sclerosis or Parkinson’s disease.     

Cluster-randomized,controlled trial of computer-based decision support for selecting long-term anti-thrombotic therapy after acute ischaemic stroke

BACKGROUND: Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance. Aim: To evaluate the influence on prescribing practice of a computer-based decision support system (CDSS) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy. DESIGN: Cluster-randomized controlled trial. METHODS: We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms, excluding those with a poor prognosis or major contraindication to anticoagulation. After observation of routine prescribing practice (6 months) in each hospital, centres were randomized for 6 months to either control (routine practice observed) or intervention (practice observed while the CDSS provided patient-specific information). We compared, between control and intervention centres, the risk reduction (estimated by the CDSS) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy, and the proportions of subjects prescribed the optimal therapy identified by the CDSS. RESULTS: Sixteen hospitals recruited 1952 subjects. When the CDSS provided information, the mean relative risk reduction attained by prescribing increased by 2.7 percentage units (95%CI -0.3 to 5.7) and the odds ratio for the optimal therapy being prescribed was 1.32 (0.83 to 1.80). Some 55% (5/9) of clinicians believed the CDSS had influenced their prescribing. CONCLUSIONS: Cluster-randomized trials provide excellent frameworks for evaluating novel clinical management methods. Our CDSS was feasible to implement and acceptable to clinicians, but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke.