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Background The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) evaluated ticagrelor compared to placebo for the prevention of myocardial infarction (MI), stroke and cardiovascular (CV) death in 19 220 patients with type 2 diabetes (T2DM) and stable coronary artery disease (CAD) with no prior myocardial infarction (MI) or stroke. THEMIS-PCI was a pre-specified subgroup of 11 154 patients who had a history of percutaneous coronary intervention (PCI) when entering the study. In THEMIS, ticagrelor reduced CV death, MI or stroke, although with an increase in major bleeding compared to aspirin alone, and there was a significant interaction between a prior history of PCI and the net benefit of ticagrelor. In the THEMIS-PCI population, ticagrelor plus aspirin provided a favourable net clinical benefit with a significant 15% reduction in all-cause death, MI, stroke, fatal bleed, or intracranial haemorrhage. Objective The objective of this analysis was to estimate the cost-effectiveness of ticagrelor for the prevention of CV events based on the results of the THEMIS-PCI population using a lifetime horizon from a Swedish healthcare perspective. Methods A lifetime Markov state transition model was developed with health states aligned to the THEMIS trial endpoints. Health state transitions were informed by parametric survival equations fitted to patient level data from THEMIS-PCI population. Treatment discontinuation rates were informed by the THEMIS-PCI population, with all patients assumed to discontinue treatment with ticagrelor after four years. The incidence of bleeding and dyspnoea were modelled as adverse events. Costs (2019 Euros) and utility data were derived from the published literature and the THEMIS-PCI population, respectively, and discounted at 3.0% annually. Probabilistic (PSA) and deterministic sensitivity analysis (DSA) were conducted to quantify uncertainty of key input parameters. Results Treatment with ticagrelor plus aspirin over four years resulted in estimated Quality Adjusted Life Year (QALY) gains of 0.09 at an incremental cost of €1,891 compared to aspirin alone. The estimated incremental cost-effectiveness ratio (ICER) was €19,959/QALY. PSA indicated that ticagrelor was cost-effective in 93% of simulations using a willingness-to-pay threshold of €47,000/QALY and DSA showed that cost-effectiveness was robust to changes in key input parameters (ICER range: €16,504 to €25,012/QALY). Conclusion Based on the results of the THEMIS trial, dual antiplatelet therapy with ticagrelor plus aspirin is likely to be a cost-effective treatment compared with aspirin alone for the prevention of CV events in patients with T2DM and CAD with a history of PCI. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

Background Serum potassium (SK+) is a vital electrolyte, which level is maintained by adjusting renal K+ excretion. Variability in SK+ has been linked to increased risk of mortality and other adverse clinical events in patients in intensive care and/or receiving haemodialysis, prompting a similar investigation in cardiovascular patients. Purpose To examine the effect of SK+ variability on all-cause mortality (ACM) and the incidence of major adverse cardiovascular events (MACE), comprising arrhythmia, [subsequent records of] HF, myocardial infarction, or stroke, in patients with heart failure (HF) or resistant hypertension (RHTN). Methods Patients aged ≥18 years with HF or RHTN were identified from the UK Clinical Practice Research Datalink (CPRD, primary care data) and linked Hospital Episode Statistics (HES, secondary care data). HF and RHTN were defined through READ codes recorded during the study period (2008-June 2018) or the five-year look-back period (2003–2007). Index date was set to 1st January 2008 or initial diagnosis; whichever occurred later. Mean SK+ and variability of measurements (quantified as standard deviation [SD] and each patient categorised as low or highly variable based on the median SD of the cohort), and crude incidence rates of ACM and MACE were estimated over a follow-up period from index date to event or end of follow-up (death, loss to follow-up or end of study, whichever was earlier). Results The eligible population included 317,135 RHTN patients and 84,210 HF patients with a mean follow-up of 6.37 (SD 3.06) and 5.01 (SD 3.20) years, respectively. In both cohorts, higher mean SK+ ≥5.0 mmol/L was associated with increased rates of ACM and MACE relative to a mean SK+ of 3.5–5 mmol/L (Table 1). High SK+ variability was associated with increased incidence of adverse outcomes, with rates consistently higher in the high SK+ variability group compared to low-variability patients with the same diagnosis and mean SK+ category (Table 1); all comparisons were statistically significant except for ACM in HF patients with mean SK+ ≥5 mmol/L. Conclusion Independently of mean SK+, increased variability in SK+ levels was associated with an increased rate of mortality and MACE in patients with RHTN or HF. Careful SK+ monitoring and management to maintain SK+ concentrations may improve the outcomes of patients with RHTN and HF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

Background Hyper- and hypokalaemia are frequent complications in patients with heart failure (HF). The association between all-cause mortality (ACM), major adverse cardiovascular events (MACE) and serum potassium (K+) has previously been characterised in a UK incident HF population, with hypo- and hyperkalaemic patients being at increased risk of adverse clinical outcomes. Purpose This study aimed to assess the generalisability and findings of previously published risk equations in a broader HF population, spanning both incident and prevalent HF cases regardless of chronic kidney disease (CKD), and to explore the relationship between duration of HF and elevated risk associated with hypo- or hyperkalaemia. Methods A retrospective cohort study was conducted using linked UK Clinical Practice Research Datalink (CPRD) GOLD and Hospital Episode Statistics (HES) data. Eligible patients included individuals ≥18 years with HF (identified using READ codes) during the study period (January 2008 to June 2018) or five-year lookback period (2003 to 2007). Patients' index date was set to 1st January 2008 for prevalent patients or date of HF diagnosis for incident patients. Adverse clinical outcomes included ACM and MACE, a composite of arrhythmia, HF, myocardial infarction and stroke. Published risk equations for ACM and MACE for incident HF without CKD were refitted to this broader study population using original covariates and model forms. Coefficient values were adjusted for the inclusion of HF duration (≤5 and >5 years). Incidence rate ratios (IRRs) were recalculated with K+ concentration 4.5 to Results The HF cohort consisted of 84,210 patients with a mean follow-up of 5.01 years. The cohort was predominantly male (53.0%), with a mean age of 77.3 years at index. Ischaemic heart disease, hypertension, atrial fibrillation and type 2 diabetes were present in 42.24%, 61.39%, 40.89% and 20.38% of the population, respectively. CKD stage 3+ was present in 39.13% of patients, with a cohort mean estimated glomerular filtration rate of 56.9 mL/min/1.73m2 at index. Crude ACM and MACE event rates were 159.5 (95% confidence interval (CI): 157.9–161.0) and 575.8 (95% CI: 572.8–578.7) per 1,000 patient years, respectively. Hypo- and hyperkalaemia were generally associated with increased risk of ACM and MACE in comparison with patients with K+ concentrations of 4.5 to Conclusion A real-world analysis of UK patients suggests that previously published associations between hypo- and hyperkalaemia and increased risk of adverse clinical outcomes in an incident HF population are generalisable to a cohort of incident and prevalent HF patients, irrespective of HF duration and the presence of comorbid CKD. Improved monitoring and management of K+ may have the potential to improve outcomes in these patients. Figure 1. IRRs of ACM and MACE Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

Background Patients with chronic kidney disease (CKD), heart failure (HF), resistant hypertension (RHTN) and diabetes are at an increased risk of hyperkalaemia (HK) which can be potentially life-threatening, as a result of cardiac arrhythmias, cardiac arrest leading to sudden death. In these patients, renin-angiotensin-aldosterone system inhibitors (RAASi), are used to manage several cardiovascular and renal conditions, and are associated with an increased risk of HK. Assessing the burden of HK in real-world clinical practice may concentrate relevant care on those patients most in need, potentially improving patient outcomes and efficiency of the healthcare system. Purpose To assess the burden of HK in a real-world population of UK patients with at least one of: RHTN, Type I or II diabetes, CKD stage 3+, dialysis, HF, or in receipt of a prescription for RAASi. Methods Primary and secondary care data for this retrospective study were obtained from the UK Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES). Eligible patients were identified using READ codes defining the relevant diagnosis, receipt of indication-specific medication, or, in the case of CKD, an estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73m2 within the study period (01 January 2008 to 30 June 2018) or in the five-year lookback period (2003–2007). The index date was defined as 01 January 2008 or first diagnosis of an eligible condition or RAASi prescription, whichever occurred latest. HK was defined as K+ ≥5.0 mmol/L; thresholds of ≥5.5 mmol/L and ≥6.0 mmol/L were explored as sensitivity analyses. Incidence rates of HK were calculated with 95% confidence intervals (CI). Results The total eligible population across all cohorts was 931,460 patients. RHTN was the most prevalent comorbidity (n=317,135; 34.0%) and dialysis the least prevalent (n=4,415; 0.5%). The majority of the eligible population were prescribed RAASi during follow-up (n=754,523; 81.0%). At a K+ threshold of ≥5.0 mmol/L, the dialysis cohort had the highest rate of HK (501.0 events per 1,000 patient-years), followed by HF (490.9), CKD (410.9), diabetes (355.0), RHTN (261.4) and the RAASi cohort (211.2) (Figure 1). This pattern was still observed at alternative threshold definitions of HK. Conclusion This large real-world study of UK patients demonstrates the burden of hyperkalaemia in high-risk patient populations from the UK. There is a need for effective prevention and treatment of HK, particularly in patients with CKD, dialysis or HF where increased incidence rates are observed which in turn will improve patient outcomes and healthcare resource usage. Figure 1. Rates of HK by condition Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

Objectives\ud The Eighth Mount Hood Challenge (held in St. Gallen, Switzerland, in September 2016) evaluated the transparency of model input documentation from two published health economics studies and developed guidelines for improving transparency in the reporting of input data underlying model-based economic analyses in diabetes.\ud \ud Methods\ud Participating modeling groups were asked to reproduce the results of two published studies using the input data described in those articles. Gaps in input data were filled with assumptions reported by the modeling groups. Goodness of fit between the results reported in the target studies and the groups’ replicated outputs was evaluated using the slope of linear regression line and the coefficient of determination (R2). After a general discussion of the results, a diabetes-specific checklist for the transparency of model input was developed.\ud \ud Results\ud Seven groups participated in the transparency challenge. The reporting of key model input parameters in the two studies, including the baseline characteristics of simulated patients, treatment effect and treatment intensification threshold assumptions, treatment effect evolution, prediction of complications and costs data, was inadequately transparent (and often missing altogether). Not surprisingly, goodness of fit was better for the study that reported its input data with more transparency. To improve the transparency in diabetes modeling, the Diabetes Modeling Input Checklist listing the minimal input data required for reproducibility in most diabetes modeling applications was developed.\ud \ud Conclusions\ud Transparency of diabetes model inputs is important to the reproducibility and credibility of simulation results. In the Eighth Mount Hood Challenge, the Diabetes Modeling Input Checklist was developed with the goal of improving the transparency of input data reporting and reproducibility of diabetes simulation model results.

Aims Insulin therapy is indicated for people with Type 1 diabetes mellitus; however, treatment‐related weight gain and hypoglycaemia represent barriers to optimal glycaemic management. This study assessed the health economic value of maintained reductions in HbA1c, BMI and hypoglycaemia incidence among the UK Type 1 diabetes population. Methods The Cardiff Type 1 Diabetes Model was used to estimate lifetime costs, life‐years and quality‐adjusted life‐years (QALYs) for individuals with Type 1 diabetes at different baseline HbA1c, BMI and hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary benefit associated with improving Type 1 diabetes management was derived at £20 000/QALY gained. Per‐person outputs were inflated to national levels using UK Type 1 diabetes prevalence estimates. Results Modelled subjects with an HbA1c of 86 mmol/mol (10.0%) were associated with discounted lifetime per‐person costs of £23 795; £12 649 of which may be avoided by maintaining an HbA1c of 42 mmol/mol (6.0%). Combined with estimated QALY gains of 2.80, an HbA1c of 42 mmol/mol (6.0%) vs. 86 mmol/mol (10.0%) was associated with a £68 621 per‐person net monetary benefit. Over 1 year, unit reductions in BMI produced £120 per‐person net monetary benefit, and up to £197 for the avoidance of one non‐severe hypoglyceamic event. Conclusions Maintained reductions in HbA1c significantly alleviate the burden associated with Type 1 diabetes in the UK. Given the influence of weight and hypoglycaemia on health economic outcomes, they must also be key considerations when assessing the value of Type 1 diabetes technologies in clinical practice., What's new? This study demonstrated the burden of inadequate Type 1 diabetes management, and quantified the value of reducing HbA1c, weight and hypoglycaemia frequency among the UK Type 1 diabetes population.Significant cost savings, quality‐adjusted life‐year gains and net monetary benefit were predicted in those who achieve HbA1c targets recommended in national guidelines; nevertheless, any incremental improvement in glycaemic management substantially reduced the burden of Type 1 diabetes mellitus on individuals and healthcare systems.Given the influence of weight and hypoglycaemia on health economic outcomes, these factors should also be key considerations when assessing the value of Type 1 diabetes technologies.

Chronic kidney disease (CKD) and end stage renal disease (ESRD) pose a significant global health burden. Approximately 40% of people with type 2 diabetes develop CKD. The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial showed a reduced rate of the composite endpoint of sustained decrease of ≥40% in estimated glomerular filtration rate (eGFR) to Disclosure P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. Funding AstraZeneca

Sodium-glucose co-transporter inhibitors have demonstrated reduced incidence of cardiovascular (CV) events, which cannot be fully explained by effects on HbA1c, body weight or blood pressure. Type 2 diabetes mellitus (T2DM) economic models link treatment-related changes in risk factor levels to long-term incidence of CV events via risk equations (RE). This study assessed the performance of commonly used CV RE in T2DM to the CV outcomes trial DECLARE-TIMI 58. Ten sets of RE were coded in MS-Excel (ADVANCE, ARIC, BRAVO, Framingham, Fremantle, New Zealand CVD, QRisk3, Swedish NDR, UKPDS 68 and 82) to predict annual probabilities of CV events and applied to baseline characteristics and 1-year treatment effects (HbA1c, weight and blood pressure) for dapagliflozin (DAPA) versus placebo (PLA) from DECLARE-TIMI 58. Predicted event rates for myocardial infarction (MI), heart failure (HF) and stroke and the relative risks (RR) associated with DAPA versus PLA were estimated and compared to the closest reported trial outcome. Of the ten sets of RE, seven predicted composite CV outcomes, demanding assumptions to predict risk of individual events; only UKPDS and BRAVO predicted all three events. When comparing trial observations against predictions averaged across RE, correlation was greater for absolute event rates (R2: 0.92) than RRs (R2: 0.42). ARIC, Fremantle and New Zealand RE considerably overpredicted risk of MI and stroke compared to the trial. RE typically underpredicted the effect of DAPA on HF (average predicted RR: 0.89 versus reported hazard ratio 0.73, CI: 0.61 to 0.88) and MI (average predicted RR: 0.93 versus reported hazard ratio 0.89, CI: 0.77 to 1.01). Existing methods of CV risk prediction evaluated in this study did not accurately predict the treatment benefits observed in DECLARE-TIMI 58. The development of DECLARE-TIMI 58-specific risk equations may be required to robustly evaluate the long-term clinical and economic impact of DAPA in T2DM. Disclosure P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. V. Foos: Employee; Self; Health Economics and Outcomes Research Ltd., IQVIA. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. Funding AstraZeneca

Risk equations (RE) from the UK Prospective Diabetes Study (UKPDS) remain the most commonly used within economic models of type 2 diabetes mellitus (T2DM). However, clinical practice has evolved since UKPDS reported and the applicability of these RE to contemporary T2DM patients is uncertain. The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial assessed cardiovascular (CV) outcomes in a broad T2DM population treated with dapagliflozin (DAPA) versus placebo (PLA). This study aimed to assess the performance of the UKPDS 82 RE in the DECLARE-TIMI 58 population. RE for myocardial infarction (MI), heart failure (HF) and stroke were applied to baseline characteristics and 12-month effects of DAPA versus PLA on HbA1c, weight and blood pressure from DECLARE-TIMI 58. Predicted annual probabilities were converted to event rates per 1,000-person years and associated relative risks (RR) for DAPA versus PLA derived for comparison to trial outcomes. Due to misalignment of the UKPDS and DECLARE-TIMI 58 endpoints, predictions of congestive heart failure were compared to observed incidence of hospitalization for HF and stroke to ischemic stroke, respectively. Predicted (study reported) rates per 1,000 person years for MI, HF and stroke were 8.15 (11.7), 2.47 (6.20) and 3.28 (6.90) for DAPA, and 8.53 (13.2), 2.59 (8.50) and 3.46 (6.80) for PLA. Predicted RR of MI, HF and stroke for DAPA versus PLA were 0.96, 0.95, 0.95, respectively, compared to reported hazard ratios of 0.89 (95% CI: 0.77, 1.01), 0.73 (0.61, 0.88) and 1.01 (0.84, 1.21) in DECLARE-TIMI 58. UKPDS 82 RE did not predict the reduction in CV events demonstrated for DAPA versus PLA based on risk factor improvements observed in DECLARE-TIMI 58. These findings add to a growing body of evidence that suggests the CV effects of sodium-glucose co-transporter inhibitors such as DAPA cannot be fully described via treatment-induced changes in conventional prognostic factors. Disclosure P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. V. Foos: Employee; Self; Health Economics and Outcomes Research Ltd., IQVIA. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. Funding AstraZeneca

Insulin-treatment in type 1 diabetes mellitus (T1DM) is associated with elevated risk of hypoglycaemia and weight gain, which may act as a barrier to achieving optimal glycaemic control. For patients inadequately controlled by insulin alone, adjunct dapagliflozin can reduce body weight and improve glycaemic control without increased risk of hypoglycaemia. This study aimed to empirically quantify the inter-relationships between hypoglycaemia, body mass index (BMI) and quality of life using DEPICT-2 trial data. A two-stage linear regression framework evaluated (1) the relationship between hypoglycaemic fear score (HFS) and the occurrence of severe hypoglycaemia, the number of documented symptomatic events and patient age, and (2) the relationship between health-related utility (EQ-5D) and prognostic factors for utility, including HFS and BMI. Model selection was based on clinically-relevant factors. A linked evidence approach correlated the relationship between treatment, hypoglycaemia incidence and HbA1c over 52-weeks, to the relationships captured within the regression models. HFS increased as a function of incidence of severe hypoglycaemia (coefficient estimate (CE): 14.62, p=0.004) and frequency of symptomatic events (log transposed, CE: 1.32, p=0.0026). In turn, increased HFS and increased BMI were both independently associated with a significant reduction in utility (CE 0.0024, p Disclosure J. Gordon: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, GlaxoSmithKline plc., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Takeda Canada, Takeda Pharmaceutical Company Limited. L.M. Beresford-Hulme: None. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. A. Tank: Employee; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd.

Objectives The hepatitis C virus (HCV) remains a significant public health issue. This study aimed to quantify the clinical and economic burden of chronic hepatitis C in the UK, stratified by disease severity, age and awareness of infection, with concurrent assessment of the impact of implementing a treatment prioritization approach. Study design and methods A previously published back projection, natural history and cost-effectiveness HCV model was adapted to a UK setting to estimate the disease burden of chronic hepatitis C and end-stage liver disease (ESLD) between 1980 and 2035. A published meta-regression analysis informed disease progression, and UK-specific data informed other model inputs. Results At 2015, prevalence of chronic hepatitis C is estimated to be 241,487 with 22.20%, 33.72%, 17.22%, 16.67% and 10.19% of patients in METAVIR stages F0, F1, F2, F3 and F4, respectively, but is estimated to fall to 193,999 by 2035. ESLD incidence is predicted to peak in 2031. Assuming all patients are diagnosed and treatment is prioritized in F3 and F4 using highly efficacious direct-acting antiviral (DAA) regimens, a 69.85% reduction in ESLD incidence is predicted between 2015 and 2035, and the cumulative discounted medical expenditure associated with the lifetime management of incident ESLD events is estimated to be £1,202,827,444. Conclusions The prevalence of chronic hepatitis C is expected to fall in coming decades; however, the ongoing financial burden is expected to be high due to an increase in ESLD incidence. This study highlights the significant costs of managing ESLD that are likely to be incurred without the employment of effective treatment approaches.

Aims To determine the impact of self-monitoring blood glucose (SMBG) strip use in patients with type 2 diabetes in the UK. Methods The study period was April 1, 2004 to July 31, 2005. Data from primary care was extracted from The Health Improvement Network database. Patients identified with diabetes and matching the inclusion criteria were defined as new users of SMBG, prevalent users, or non-users. Patients were also defined as treated with insulin, with oral agents (OA), or not pharmacologically treated. Change in glycosylated hemoglobin (HbA1c) at baseline and after 12 months was compared. Results 2559 patients met the inclusion criteria. For new users, HbA1c fell by 0.59% (P=0.399) for those treated with insulin, 1.52% (P

This retrospective cohort-based study assessed the change in glycated haemoglobin A1C (HbA 1C) in patients with type 2 diabetes, with existing prescriptions for oral antidiabetic drugs (OADs), prescribed insulin versus those prescribed subsequent OADs. A cohort of patient records drawn from the The Health Improvement Network (THIN) database was stratified by maximum concurrent number of OADs. Of 128,568 unique patient records identified, 67.7% (n=87,057) had received at least one OAD, 17.4% (n=15,138) of these patients progressed to insulin therapy. Mean HbA1C at insulin initiation was 9.5% (one OAD), 9.6% (two), 9.7% (three) and 10.1% (four), with an average HbA 1C increase of 0.7% prior to insulin initiation. The greatest improvement in HbA1C was achieved with insulin therapy. A threshold HbA 1C value of 8.5% above which OAD escalation is unlikely to achieve a target HbA1C ≤ 7.0% is seen. In patients not achieving HbA1C targets with OADs only, insulin-based regimens should be considered in preference to adding more or multiple OADs. Br J Diabetes Vasc Dis 2010;10:178—182.

Aim: The attainment of near-normal glycaemia is an important feature in reducing complications in people with type 2 diabetes. Current treatment pathways advocate a failure-driven therapy algorithm for blood-glucose lowering that leads to the sequential addition of therapies. The addition and combination of multiple blood-glucose lowering agents may be associated with significant side effects, such as weight gain and hypoglycaemia, resulting in a detrimental quality of life. The objective of this study is to quantify the overall costs and quality-adjusted life years (QALY) associated with therapy escalation via oral only treatment strategies with different adverse event profiles as a function of target HbA1c achievement. Methods: A previously published model was adapted to run as a non-terminating simulation model. The model is designed to evaluate the cost utility of treatment strategies in a population of type 2 diabetes mellitus patients. Model outputs include incidence of micro- and macrovascular complications, hypoglycaemia and diabetes-specific and all-cause mortality. Results: The total number of vascular events predicted by the model varied little across the four treatment strategies because of the glycaemic profile associated with each therapy strategy being similar. The strategy with sequential addition of thiazolidinediones (TZDs) and sulphonylureas (SUs) to metformin (MF) was associated with greatest predicted hypoglycaemia burden. The addition of SU and dipeptidyl peptidase (DPP-4) inhibitors to MF was associated with the highest estimated QALYs. Conclusions: A treatment strategy involving the sequential addition of SU and TZD to first-line MF therapy is associated with the lowest cost and lowest gain across a population, whereas addition of TZD and SU sequentially to first-line MF therapy resulted in the highest cost and incrementally less QALY gain when compared with treatment strategies involving the addition of a DPP-4 inhibitor and SU to first-line MF (irrespective of the treatment sequence) that were associated with both less cost and greatest QALY gain.

Objective To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. Design An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. Setting Fifty-three fertility clinics in 13 European countries and Israel. Patient(s) Women indicated for treatment with IVF (N = 986), aged 18–38, participating in double-blind, randomized controlled trials. Intervention(s) Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). Main Outcome Measure(s) Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. Result(s) HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were £2408 (95% confidence interval [CI], £2392, £2421) and £2660 (95% CI £2644, £2678), respectively. The mean cost saving of £253 per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. Conclusion(s) Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

OBJECTIVE. To evaluate the impact of the overactive bladder (OAB) on quality of life and health-related utility. PATIENTS AND METHODS. In a study conducted in Cardiff and Vale NHS Trust, patients were identified from an academic urology unit inpatient database for admissions and sent a postal survey. The survey pack comprised questionnaires on demography, urological functioning, health utility (EQ5Dindex), and health-related quality of life (Short Form-36, SF36). Respondents were classified according to general urinary status, frequency, urgency, and stress incontinence. RESULTS. Of 2193 surveys dispatched, 609 (27.8%) were returned; of these patients, 52% had incontinence, of whom 83% had both frequency and urgency, and 60% stress incontinence. Patients with stress incontinence reported a mean (sd) EQ5Dindex of 0.578 (0.331), compared to 0.714 (0.281) for all other patients (P < 0.001). From the SF36, respondents scored lowest in the role physical domain and highest in the mental domain, with mean scores of 33.8 and 72.1, respectively. Multivariate analysis of SF36 and EQ5Dindex scores, controlling for age, gender and body mass index, showed that incontinence was associated with a notable reduction in the EQ5Dindex and SF36 scores across all domains. CONCLUSION. This study showed a significant reduction in quality of life for all patient groups with OAB; in particular, stress incontinence had the greatest impact.

Objective: To evaluate how well patients with non-valvar atrial fibrillation (NVAF) were maintained within the recommended international normalised ratio (INR) target of 2.0–3.0 and to explore the relation between achieved INR control and clinical outcomes. Design: Record linkage study of routine activity records and INR measurements. Setting: Cardiff and the Vale of Glamorgan, South Wales, UK. Participants: 2223 patients with NVAF, no history of heart valve replacement, and with at least five INR measurements. Main outcome measures: Mortality, ischaemic stroke, all thromboembolic events, bleeding events, hospitalisation, and patterns of INR monitoring. Results: Patients treated with warfarin were outside the INR target range 32.1% of the time, with 15.4% INR values > 3.0 and 16.7% INR values < 2.0. However, the quartile with worst control spent 71.6% of their time out of target range compared with only 16.3% out of range in the best controlled quartile. The median period between INR tests was 16 days. Time spent outside the target range decreased as the duration of INR monitoring increased, from 52% in the first three months of monitoring to 30% after two years. A multivariate logistic regression model showed that a 10% increase in time out of range was associated with an increased risk of mortality (odds ratio (OR) 1.29, p < 0.001) and of an ischaemic stroke (OR 1.10, p = 0.006) and other thromboembolic events (OR 1.12, p < 0.001). The rate of hospitalisation was higher when INR was outside the target range. Conclusions: Suboptimal anticoagulation was associated with poor clinical outcomes, even in a well controlled population. However, good control was difficult to achieve and maintain. New measures are needed to improve maintenance anticoagulation in patients with NVAF.

Aims The Framingham risk equations are widely used to estimate risk of coronary heart disease (CHD). The purpose of this study was to evaluate the reliability of these equations in predicting CHD risk in people with diabetes and the reliability of using imputed mean HDL-cholesterol values. Methods Data describing the baseline characteristics of recognized CHD risk factors for 938 people aged 30–74 years were extracted from the Cardiff Diabetes Database. Data describing CHD events were available for up to 4 years following the baseline year (1996). Several mathematical techniques were used to assess the reliability of predictions provided by the Framingham equations in this population. Results Thirty-four percent of males and 25% of females who experienced CHD events had a predicted 10-year CHD risk ≥ 30%. Seventy-five percent of males and 58% of females had a predicted 10-year CHD risk ≥ 20%. Using imputed HDL-cholesterol values, 26% of males and 6% of females who later developed CHD events had a 10-year CHD risk ≥ 30%. Using imputed HDL-cholesterol values, the CHD risk predicted by the Framingham equations consistently underestimated the actual risk of CHD events. However, refitting the Framingham risk equations to the Cardiff data resulted in only marginal improvements in discriminatory capabilities. Conclusions The Framingham risk equations can be unreliable when applied to the diabetic population, tending to underestimate an individual's probability of progressing to CHD; the equations perform marginally better in women than in men. The use of imputed mean HDL-cholesterol values improved the reliability of the estimates of risk.

In addition to the clinical management of blood supplies, the UK National Blood Service (NBS) examines short-term supply and demand to predict any potential shortages in blood supplies. However, very little data are available on the medium- and long-term trends. This paper describes blood product use in a United Kingdom Hospital Trust in 1999 and combines it with donor information to project the effect of demographic changes on demand and supply over the next 25 years. Overall, 2801 (4%) inpatients received transfusions of blood products. The proportion of inpatients receiving blood products increased with age. Patients aged >70 years used 46% of the total blood product supply, whereas patients aged