Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients.

Atrial fibrillation (AF) carries an increased risk of ischaemic stroke, and oral anticoagulation with warfarin can reduce this risk. The objective of this study was to evaluate the association between time in therapeutic International Normalised Ratio (INR) range when receiving warfarin and the risk of stroke and mortality. The study cohort included AF patients aged 40 years and older included in the UK General Practice Research Database. For patients treated with warfarin we computed the percentage of follow-up time spent within therapeutic range. Cox regression was used to assess the association between INR and outcomes while controlling for patient demographics, health status and concomitant medication. The study population included 27,458 warfarin-treated (with at least 3 INR measurements) and 10,449 patients not treated with antithrombotic therapy. Overall the warfarin users spent 63% of their time within therapeutic range (TTR). This percentage did not vary substantially by age, sex and CHA2DS2-VASc score. Patients who spent at least 70% of time within therapeutic range had a 79% reduced risk of stroke compared to patients with ≤30% of time in range (adjusted relative rate of 0.21; 95% confidence interval 0.18-0.25). Mortality rates were also significantly lower with at least 70% of time spent within therapeutic range. In conclusion, good anticoagulation control was associated with a reduction in the risk of stroke.

Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: a Canadian payer perspective.

Oral dabigatran etexilate is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) in whom anticoagulation is appropriate. Based on the RE-LY study we investigated the cost-effectiveness of Health Canada approved dabigatran etexilate dosing (150 mg bid for patients <80 years, 110 mg bid for patients ≥80 years) versus warfarin and "real-world" prescribing (i.e. warfarin, aspirin, or no treatment in a cohort of warfarin-eligible patients) from a Canadian payer perspective. A Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events [primary and recurrent ischaemic strokes, systemic embolism, transient ischaemic attack, haemorrhage (intracranial, extracranial, and minor), acute myocardial infarction and death] and resulting functional disability. Acute event costs and resulting long-term follow-up costs incurred by disabled stroke survivors were based on a Canadian prospective study, published literature, and national statistics. Clinical events, summarized as events per 100 patient-years, quality-adjusted life years (QALYs), total costs, and incremental cost effectiveness ratios (ICER) were calculated. Over a lifetime, dabigatran etexilate treated patients experienced fewer intracranial haemorrhages (0.49 dabigatran etexilate vs. 1.13 warfarin vs. 1.05 "real-world" prescribing) and fewer ischaemic strokes (4.40 dabigatran etexilate vs. 4.66 warfarin vs. 5.16 "real-world" prescribing) per 100 patient-years. The ICER of dabigatran etexilate was $10,440/QALY versus warfarin and $3,962/QALY versus "real-world" prescribing. This study demonstrates that dabigatran etexilate is a highly cost-effective alternative to current care for the prevention of stroke and systemic embolism among Canadian AF patients.

Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism in patients aged over 75 years or with moderate renal impairment undergoing total knee or hip replacement.

Oral dabigatran etexilate is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing total knee replacement or total hip replacement. We investigated the cost-effectiveness of the 150 mg once daily (od) dose recommended for patients aged over 75 or with moderate renal impairment, from a United Kingdom National Health Service perspective. Dabigatran etexilate was compared with subcutaneous enoxaparin 40 mg od, using a decision model. Risks for VTE and bleeding were derived from subgroup analyses of the phase III trials. Dabigatran etexilate was less costly than enoxaparin; cost savings varied from pound62 to pound274 (base-case analyses) and were primarily due to differences in administration costs. Results were robust across a range of sensitivity analyses. Dabigatran etexilate 150 mg od is cost saving compared with enoxaparin 40 mg od in patients aged over 75years and in patients with moderate renal impairment, with comparable efficacy and safety.

How much does international normalized ratio monitoring cost during oral anticoagulation with a vitamin K antagonist? A systematic review.

Next-generation oral anticoagulants offer the potential for effective prevention and treatment of thrombosis without the need for repeated monitoring of the international normalized ratio (INR). This systematic review evaluated the costs associated with INR monitoring tests performed as part of the standard management of oral anticoagulation with vitamin K antagonists. Studies published in or after 1990 reporting the costs of INR monitoring were identified from bibliographic databases and manual searches of reference lists. Cost data were extracted and inflated to the year 2006 before purchasing power parity conversion to US dollars. A total of 29 studies reported the cost of one INR test, which was shown to range from $6.19 to $145.70. Cost estimates were based on various combinations of direct medical costs, such as healthcare contacts, equipment, laboratory tests, clerical costs (postage and stationery), telephone calls, quality control, training/education and patient transportation, and indirect costs, such as time lost from work. In conclusion, the cost of INR monitoring varied substantially between studies depending on the monitoring modality and setting, and the cost categories included. When selecting a published estimate, healthcare decision makers should ensure that the chosen estimate reflects local service provision as closely as possible.

Cost-effectiveness of venous thromboembolism prophylaxis in total hip and knee replacement surgery: the evolving application of health economic modelling over 20 years.

OBJECTIVES: In the last two decades, there has been considerable evolution of methods for cost-effectiveness modelling. Some of the first models were developed in the area of venous thromboembolism (VTE) prophylaxis. Hence, this area can serve as an important example to illustrate evolving standards. Our objectives are to document evolving methodology by describing VTE models, assess their critical strengths and weaknesses, and inform future advances for models in this therapeutic area. RESEARCH DESIGN AND METHODS: A systematic review of economic models of primary VTE prevention following hip and knee replacement surgery was undertaken. Electronic searches of PubMed, EMBASE, the Cochrane library, and grey literature were conducted (1985-2006). Reference lists of included articles and reviews were examined for relevant studies. RESULTS: Twenty-nine cost-effectiveness models were identified. Nineteen other cost-effectiveness analyses were excluded because they were not model-based; 16 were simple cost calculations and three were analyses of resource use data collected alongside clinical trials. The majority of models (24) were constructed as decision trees, frequently utilising previously published model structures, with some adaptation for new comparators, and/or addition of relevant events omitted by earlier models (e.g., bleeding due to prophylactic treatment). Later models have included Markov processes to model potential long-term consequences of VTE (recurrent VTE and post-thrombotic syndrome) over longer time horizons. Systematic identification of clinical evidence and more sophisticated analysis methods (e.g., Bayesian mixed-treatment comparisons and probabilistic sensitivity analyses) have recently been introduced. CONCLUSIONS: Model structures have evolved substantially in this highly studied therapeutic area, with improvements made to the model structure, the comprehensiveness of clinical evidence included, and the underlying calculation methodology.

Effect of setting, monitoring intensity and patient experience on anticoagulation control: a systematic review and meta-analysis of the literature.

OBJECTIVES: To investigate the relationship between time spent in the recommended target International Normalised Ratio (INR) range and the setting and intensity of anti coagulant monitoring, in both treatment-experienced and treatment-naive atrial fibrillation (AF) patients receiving oral anticoagulation (OAC) therapy for the prevention of ischaemic stroke. RESEARCH DESIGN AND METHODS: Systematic review of published studies on participants with atrial fibrillation on anticoagulation therapy. We compared frequent monitoring (well-controlled, according to a strict protocol) versus infrequent monitoring (frequency representative of routine clinical practice), specialised care versus usual care, and naive versus prior anticoagulant use. Meta-analysis was performed using a random effects model. RESULTS: 36 studies were included, 22 (primary data) of AF patients managed in line with the consensus guidelines target INR range of 2.0-3.0, and 14 studies (secondary data) of mixed patient groups, including AF, with an INR target of 2.0-3.5. Both data sets were combined for sensitivity analysis. Pooled mean time in INR range was 59.1% (95% CI: 55.5, 62.8%) and 64.3% (95% CI: 60.5, 68.0%) for infrequent monitoring and frequent monitoring, respectively. Significantly more time was spent in range in specialist care settings compared to usual care: +11.3% (95% CI: 0.1-21.7%). Naive OAC users spent less time in range 56.5% (95% CI: 45.5-67.5%) than existing users 61.2% (95% CI: 57.2-65.2%). All of these differences were found to be significant in the sensitivity analyses. CONCLUSIONS: INR control is variable and dependent on monitoring intensity and duration of anticoagulant therapy.

Economic impact of tibolone compared with continuous-combined hormone replacement therapy. In the management of postmenopausal women with climacteric symptoms in the UK.

OBJECTIVE: To estimate the economic impact of using tibolone 2.5 mg compared with 17 beta-estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA) in postmenopausal women with climacteric symptoms. DESIGN AND SETTING: This was a modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: The clinical outcomes from a previously reported trial were used as the clinical basis for the analysis, which showed that 48 weeks' treatment with tibolone and E2/NETA significantly alleviated the climacteric symptoms experienced by postmenopausal women. These data were combined with resource utilisation estimates derived from a panel of 10 GPs and 3 gynaecologists, enabling us to construct a Markov model depicting changes in the health status of postmenopausal women. The model was used to estimate the expected NHS costs and consequences after 48 weeks' treatment with tibolone and E2/NETA. MAIN OUTCOME MEASURES AND RESULTS: The mean expected direct healthcare cost of using tibolone and E2/NETA to manage postmenopausal women for 48 weeks was estimated to be 260 Pounds and 239 Pounds (1997/1998 prices) per patient, respectively. Starting hormone replacement therapy (HRT) with tibolone instead of E2/NETA was equally effective in alleviating climacteric symptoms (65.9 and 62.2%, respectively; p = 0.516) over 48 weeks and significantly reduced the incidence of vaginal bleeding by 36% (p < 0.0001) and breast tenderness by 57% (p < 0.0001) for a mean additional cost of 21 Pounds (ranging between -3 Pounds and 42 Pounds) per patient. The acquisition cost of HRT was the primary cost driver for tibolone-treated patients, whereas the cost of managing adverse events was the primary cost driver for E2/NETA-treated patients. CONCLUSIONS: The true cost of prescribing tibolone and E2/NETA is impacted on by a broad range of resources, not only drug acquisition costs. Although the acquisition cost of tibolone is higher than that of E2/NETA, the difference in the expected NHS cost of the first year of treatment between the 2 HRTs is negligible. This is because of the higher incidence of adverse events among E2/NETA-treated patients, which also results in a higher continuation rate among tibolone-treated patients. Factors such as patient preferences should also be taken into consideration so that treatment choices are not decided solely on the basis of acquisition costs.

Annual cost of erectile dysfunction to UK Society.

OBJECTIVE: The objective of this study was to estimate the annual socioeconomic burden imposed by erectile dysfunction (ED) on UK society. DESIGN AND SETTING: Health service resource use attributable to ED during 1997/1998 was obtained from appropriate databases and a panel of 22 hospital specialists comprising urologists, genito-urinary physicians, diabetologists and sexual health physicians. National unit resource costs at 1996/1997 prices were applied to the resource use data to estimate the annual National Health Service (NHS) cost of managing ED. A structured questionnaire pertaining to direct costs and absenteeism from work attributable to ED was mailed to a randomly selected sample of 5000 individuals who experience ED. MAIN OUTCOME MEASURES AND RESULTS: During 1997/1998, the annual NHS cost was estimated to be 43.9 Pounds million for managing 113,600 men with ED. Outpatient visits were the major cost driver, accounting for 65% of the annual cost. Drugs prescribed by general practitioners (GPs) accounted for a further 25%. GP consultations and penile prosthetic surgery each accounted for 4%. Tests initiated by GPs accounted for 2%, while other resources accounted for less than 1%. The annual cost was sensitive to the number of outpatient visits and, to a lesser extent, to the number of prescriptions for ED treatments, but insensitive to changes in use of the other resources. Completed questionnaires were received from 23% (n = 1141) of the sample of individuals who experience ED. From the survey, it was estimated that the NHS managed 35% of individuals with ED in the last year. Assuming this to be representative, the total potential population of individuals with ED in the UK was estimated to be approximately 324,600 men. The total population of individuals with ED (n = 324,600 men) was estimated to incur 7.0 Pounds million annually in direct costs attributable to ED and to lose 19,630 days a year from work as a result of their ED, costing society 2.2 Pounds million in lost gross domestic product. CONCLUSIONS: ED imposes a relatively small burden on UK society--53 Pounds million. Of this, 83% is borne by the NHS and 13% by patients. Indirect costs to society due to lost productivity account for the remaining 4%. The total NHS cost is strongly influenced by the number of hospital outpatient visits. Therefore, the future burden will depend largely on patients' eligibility to receive ED treatments on the NHS.

An overview of workers' compensation.

The authors compare and contrast the U.S. and Canadian systems; describe the roles of government, employers and employees, and insurance providers; examine the economics of workplace risk; assess different systems in six states and two provinces; and indicate challenges to be met.