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Aims: To quantify the productivity burden of cardiovascular disease (CVD) in type 2 diabetes and the potential benefits of improved CVD risk factor control., Methods: We designed models to quantify the productivity burden (using the productivity-adjusted life-year; PALY) of CVD in Australians with type 2 diabetes aged 40-69 years from 2023-2032. PALYs were ascribed a financial value equivalent to gross domestic product (GDP) per full-time worker (AU$204,167 (€124,542)). The base-case model was designed to quantify the productivity burden of CVD in the target population. Then, other hypothetical scenarios were simulated to estimate the potential productivity gains resulting from improved control of risk factors. These scenarios included reductions in systolic blood pressure (SBP), number of smokers, total cholesterol, and incidence of type 2 diabetes. All future costs and outcomes were discounted at an annual rate of 5%., Results: In the base-case (i.e. current projections), the estimated total PALYs lost due to CVD in type 2 diabetes were 1.21 million (95%CI (1.10-1.29 million), contributing to an AU$258.93 (€157.94) billion (95%CI (AU$258.73-261.69 (€157.83-159.63) billion) lost in the country's GDP. If there were reductions in SBP, number of smokers, total cholesterol, and incidence of type 2 diabetes, there would be gains of 7,889, 28,971, 7,117, and 320,124 PALYs, respectively. These improvements would also lead to economic gains of AU$1.72 (€1.05) billion, AU$6.21 (€3.79) billion, AU$1.55 billion (€947.33 million), and AU$68.34 (€41.69) billion, respectively., Conclusions: Targeted "early lifestyle" strategies that can prevent CVD in Australians with type 2 diabetes are likely positively impact Australian health and work productivity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Myocardial infarction (MI) remains a major health burden in Australia. Yet the future burden of MI has not been extensively studied for the Australian population., Methods and Results: A multistate lifetable model was constructed to estimate the lifetime risk of MI and project the health burden of MI for the Australian population aged between 40 and 100 years over a 20-year period (2019-2038). Data for the model were primarily sourced from the Victorian-linked dataset and supplemented with other national data. The lifetime risk of MI at age 40 was estimated as 24.4% for males and 13.2% for females in 2018. From 2019 to 2038, 891 142 Australians were projected to develop incident MI. By 2038, the model estimated there would be 702 226 people with prevalent MI, 51 262 incident non-fatal MI, and 3717 incident fatal MI; these numbers represent a significant increase compared to the 2019 estimates, with a 27.0% (148 827), 62.0% (19 629), and 104.7% (1901) rise, respectively. Projected years of life lived (YLL) (5% discount) accrued by the Australian population was 174 795 232 (84 356 304 in males and 90 438 928 in females), with 7 657 423 YLL among people with MI (4 997 009 in males and 2 660 414 in females)., Conclusion: The burden of MI was projected to increase between 2019 and 2038 in Australia. The outcomes of the model provide important information for decision-makers to prioritize population-wide prevention strategies to reduce the burden of MI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: People in remote areas may have more difficulty accessing healthcare following myocardial infarction (MI) than people in metropolitan areas. We determined whether remoteness was associated with initial and 12-month use of secondary prevention medications following MI in Victoria, Australia., Methods and Results: We included all people alive at least 90 days after discharge following MI between July 2012 and June 2017 in Victoria, Australia (n = 41 925). We investigated dispensing of P2Y12 inhibitors (P2Y12i), statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs), and beta-blockers within 90 days after discharge. We estimated 12-month medication use using proportion of days covered (PDC). Remoteness was determined using the Accessibility/Remoteness Index of Australia (ARIA). Data were analysed using adjusted parametric regression models stratified by ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). There were 10 819 STEMI admissions and 31 106 NSTEMI admissions. Following adjustment across NSTEMI and STEMI, there were no medication classes dispensed in the 90-day post-discharge that differed in a clinically significant way from the least remote (ARIA = 0) to the most remote (ARIA = 4.8) areas. The largest difference for NSTEMI was ACEI/ARB, with 71% (95% confidence interval 70-72%) vs. 80% (76-83%). For STEMI, it was statins with 89% (88-90%) vs. 95% (91-97%). Predicted PDC for STEMI and NSTEMI was not clinically significant across remoteness, with the largest difference in NSTEMI being P2Y12i with 48% (47-50%) vs. 55% (51-59%), and in STEMI, it was ACEI/ARB with 68% (67-69%) vs. 76% (70-80%)., Conclusion: Remoteness does not appear to be a clinically significant driver for medication use following MI. Possible differences in cardiovascular outcomes in metropolitan and non-metropolitan areas are not likely to be explained by access to secondary prevention medications., Competing Interests: Conflict of interest: A.C.L., Z.A., D.P., and J.I.M. have no conflicts to declare relevant to this publication. J.I. has received grants from the NHMRC, National Breast Cancer Foundation, Dementia Australia Research Foundation, AstraZeneca. and Amgen. J.S.B. is supported by a National Health and Medical Research Council (NHMRC) Boosting Dementia Research Leadership Fellowship and has received grant funding or consulting funds from the NHMRC, Medical Research Future Fund, Victorian Government Department of Health, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Programme, Amgen, and several aged care provider organizations unrelated to this work. All grants and consulting funds were paid to the employing institution., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflict of interest: ZA and JIM declare no conflict of interest. DL declares grants from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Pfizer and Sanofi, and past participation in advisory boards and/or receipt of honoraria from Abbvie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Edwards Lifesciences, Novartis, Pfizer, Sanofi and Shire, outside the submitted work. SJN has received research support and/or honoraria for Amgen, AstraZeneca, Eli Lilly, Esperion, Novartis, Merck, Pfizer, Iowa and Sanofi-Regeneron.

Background: older adults in aged care account for 30% of the population burden of hip fractures. Nutritional interventions to correct under nutrition reduce these debilitating fractures, perhaps partly by reducing falls and slowing deterioration in bone morphology., Objective: to determine whether a nutritional approach to fracture risk reduction in aged care homes is cost-effective., Design: cost-effectiveness was estimated based on results from a prospective 2-year cluster-randomised controlled trial and secondary data. Intervention residents consumed a total of 3.5 daily servings of milk, yoghurt and/or cheese, resulting in 1,142 mg of calcium and 69 g of protein compared with the daily intakes of 700 mg of calcium and 58 g of protein consumed by the control group., Setting: fifty-six aged care homes., Participants: residents for 27 intervention (n = 3,313) and 29 control (n = 3,911) homes., Methods: ambulance, hospital, rehabilitation and residential care costs incurred by fracture were estimated. The incremental cost-effectiveness ratios per fracture averted within a 2-year time horizon were estimated from the Australian healthcare perspective applying a 5% discount rate on costs after the first year., Results: intervention providing high-protein and high-calcium foods reduced fractures at a daily cost of AU$0.66 per resident. The base-case results showed that the intervention was cost-saving per fracture averted, with robust results in a variety of sensitivity and scenario analyses. Scaling the benefits of intervention equates to a saving of AU$66,780,000 annually in Australia and remained cost-saving up to a daily food expenditure of AU$1.07 per resident., Conclusions: averting hip and other non-vertebral fractures in aged care residents by restoring nutritional inadequacy of protein and calcium is cost-saving., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Aims: The aim of this study was to assess the impact and cost-effectiveness of offering population genomic screening to all young adults in Australia to detect heterozygous familial hypercholesterolaemia (FH)., Methods and Results: We designed a decision analytic Markov model to compare the current standard of care for heterozygous FH diagnosis in Australia (opportunistic cholesterol screening and genetic cascade testing) with the alternate strategy of population genomic screening of adults aged 18-40 years to detect pathogenic variants in the LDLR/APOB/PCSK9 genes. We used a validated cost-adaptation method to adapt findings to eight high-income countries. The model captured coronary heart disease (CHD) morbidity/mortality over a lifetime horizon, from healthcare and societal perspectives. Risk of CHD, treatment effects, prevalence, and healthcare costs were estimated from published studies. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio (ICER), discounted 5% annually. Sensitivity analyses were undertaken to explore the impact of key input parameters on the robustness of the model. Over the lifetime of the population (4 167 768 men; 4 129 961 women), the model estimated a gain of 33 488years of life lived and 51 790 QALYs due to CHD prevention. Population genomic screening for FH would be cost-effective from a healthcare perspective if the per-test cost was ≤AU$250, yielding an ICER of

Aims: To estimate the health and economic burden of new and established cardiovascular disease from 2020 to 2029 in Australia., Methods and Results: A two-stage multistate dynamic model was developed to predict the burden of the incident and prevalent cardiovascular disease, for Australians 40-90 years old from 2020 to 2029. The model captured morbidity, mortality, years of life lived, quality-adjusted life years, healthcare costs, and productivity losses. Cardiovascular risk for the primary prevention population was derived using Australian demographic data and the Pooled Cohort Equation. Risk for the secondary prevention population was derived from the REACH registry. Input data for costs and utilities were extracted from published sources. All outcomes were annually discounted by 5%. A number of sensitivity analyses were undertaken to test the robustness of the study. Between 2020 and 2029, the model estimates 377 754 fatal and 991 375 non-fatal cardiovascular events. By 2029, 1 061 756 Australians will have prevalent cardiovascular disease (CVD). The population accrued 8 815 271 [95% uncertainty interval (UI) 8 805 083-8 841 432] years of life lived with CVD and 5 876 975 (5 551 484-6 226 045) QALYs. The total healthcare costs of CVD were projected to exceed Australian dollars (AUD) 61.89 (61.79-88.66) billion, and productivity losses will account for AUD 78.75 (49.40-295.25) billion, driving the total cost to surpass AUD 140.65 (123.13-370.23) billion., Conclusion: Cardiovascular disease in Australia has substantial impacts in terms of morbidity, mortality, and lost revenue to the healthcare system and the society. Our modelling provides important information for decision making in relation to the future burden of cardiovascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

People with epilepsy have variable and dynamic trajectories in response to antiseizure medications. Accurately modelling long-term treatment response will aid prognostication at the individual level and health resource planning at the societal level. Unfortunately, a robust model is lacking. We aimed to develop a Markov model to predict the probability of future seizure-freedom based on current seizure state and number of antiseizure medication regimens trialled. We included 1795 people with newly diagnosed epilepsy who attended a specialist clinic in Glasgow, Scotland, between July 1982 and October 2012. They were followed up until October 2014 or death. We developed a simple Markov model, based on current seizure state only, and a more detailed model, based on both current seizure state and number of antiseizure medication regimens trialled. Sensitivity analyses were performed for the regimen-based states model to examine the effect of regimen changes due to adverse effects. The model was externally validated in a separate cohort of 455 newly diagnosis epilepsy patients seen in Perth, Australia, between May 1999 and May 2016. Our models suggested that once seizure-freedom was achieved, it was likely to persist, regardless of the number of antiseizure medications trialled to reach that point. The likelihood of achieving long-term seizure-freedom was highest with the first antiseizure medication regimen, at approximately 50%. The chance of achieving seizure-freedom fell with subsequent regimens. Fluctuations between seizure-free and not seizure-free states were highest earlier on but decreased with chronicity of epilepsy. Seizure-freedom/recurrence risk tables were constructed with these probability data, similar to cardiovascular risk tables. Sensitivity analyses showed that the general trends and conclusions from the base model were maintained despite perturbing the model and input data with regimen changes due to adverse effects. Quantitative comparison with the external validation cohort showed excellent consistency at Year 1, good at Year 3 and moderate at Year 5. Quantitative models, as used in this study, can provide pertinent clinical insights that are not apparent from simple statistical analysis alone. Attaining seizure freedom at any time in a patient's epilepsy journey will confer durable benefit. Seizure-freedom risk tables may be used to individualize the prediction of future seizure control trajectory., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The Comparison of Sacubitril-Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilised from an Acute Heart Failure Episode (PIONEER-HF) trial demonstrated significant reductions in N-terminal pro-B-type natriuretic peptide. Our study explored the cost-effectiveness of the use of sacubitril-valsartan versus enalapril in acute decompensated heart failure from the Australian healthcare perspective., Methods: A Markov model was designed using data from the PIONEER-HF trial to model the clinical progress and costs of patients over a lifetime time horizon. The model consisted of three health states: 'alive and event-free', 'alive after non-fatal hospitalisation for acute decompensated heart failure' or 'dead'. Costs and utilities were estimated from published sources. The cost of sacubitril-valsartan (per the Australian pharmaceutical benefits schedule) was AU$7.08/day. Outcomes of interest were the incremental cost-effectiveness ratios in terms of cost per quality-adjusted life year gained and cost per year of life saved. Cost and benefits were discounted at 5.0% per annum., Results: Compared to enalapril, sacubitril-valsartan was estimated to cost an additional AU$7464 (discounted) per person, but lead to 0.127 years of life saved (discounted) and 0.096 quality-adjusted life years gained (discounted) over a lifetime analysis. These equated to incremental cost-effectiveness ratios of AU$58,629/year of life saved (US$41,795, EU€58,629, GBP£32,001) and AU$77,889/quality-adjusted life year gained (US$55,526, EU€49,202, GBP£42,504). We have assumed a threshold of AU$50,000/quality-adjusted life year gained to suggest cost-effectiveness., Conclusions: At its current acquisition price, sacubitril-valsartan in comparison to enalapril is not likely to be cost-effective in the management of acute decompensated heart failure in Australia. A price reduction of more than 25% would confer cost-effectiveness., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aim: To assess the cost-effectiveness of dapagliflozin in addition to standard care versus standard care alone in patients with chronic heart failure and reduced ejection fraction., Methods: A Markov model was constructed based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial to assess the clinical outcomes and costs of 1000 hypothetical subjects with established heart failure and reduced ejection fraction. The model consisted of three health states: 'alive and event-free', 'alive after non-fatal hospitalisation for heart failure' and 'dead'. Costs and utilities were estimated from published sources. The main outcome was the incremental cost-effectiveness ratio per quality-adjusted life-year gained. An Australian public healthcare perspective was employed. All outcomes and costs were discounted at a rate of 5% annually., Results: Over a lifetime horizon, the addition of dapagliflozin to standard care in patients with heart failure and reduced ejection fraction prevented 88 acute heart failure hospitalisations (including readmissions) and yielded an additional 416 years of life and 288 quality-adjusted life-years (discounted) at an additional cost of A$3,692,440 (discounted). This equated to an incremental cost-effectiveness ratio of A$12,482 per quality-adjusted life-year gained, well below the Australian willingness-to-pay threshold of A$50,000 per quality-adjusted life-year gained. Subanalyses in subjects with and without diabetes resulted in similar incremental cost-effectiveness ratios of A$13,234 and A$12,386 per quality-adjusted life-year gained, respectively., Conclusion: Dapagliflozin is likely to be cost-effective when used as an adjunct therapy to standard care compared with standard care alone for the treatment of chronic heart failure and reduced ejection fraction., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: The aim of this study was to estimate the cost-effectiveness, from the perspective of the Australian public healthcare system, of icosapent ethyl in combination with statin therapy compared with statin alone for the prevention of cardiovascular disease., Methods and Results: A Markov model populated with data from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial was designed to predict the effectiveness and costs of icosapent ethyl in combination with statins compared with statins alone over a 20-year time horizon. Data inputs for costs and utilities were sourced from published sources. The annual costs of icosapent ethyl were assumed to be AUD1637 (USD2907) per person. All future costs and outcomes were discounted annually by 5%. The main outcome of interest was incremental cost-effectiveness ratios in terms of cost per quality adjusted life year (QALY) gained and per year of life saved (YoLS). Over a 20-year time horizon, compared with statin alone, icosapent ethyl in combination with statin was estimated to cost an additional AUD$13,022 per person, but led to 0.338 YoLS and 0.289 QALYs gained (all discounted). These equated to incremental cost-effectiveness ratios of AUD45,036 per QALY gained and AUD38,480 per YoLS. Sub-analyses for primary and secondary prevention were AUD96,136 and AUD35,935 per QALY gained, respectively. The results were sensitive to time-horizon, age related trends and the acquisition price of icosapent ethyl., Conclusion: Compared with statin alone, icosapent ethyl in combination with statin therapy is likely to be cost-effective in the prevention of cardiovascular disease assuming a willingness-to-pay threshold of AUD50,000 per QALY gained, especially in the secondary preventive setting., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: To determine the impact of preventing new (incident) cases of coronary heart disease (CHD) on years of life and productivity, using the novel measure 'productivity-adjusted life year' (PALY), over the next 10 years., Methods and Results: A dynamic life table model was constructed for the total Australian working-age population (15-69 years) over 10 years (2020-2029), separated by CHD status. Productivity estimates were sourced from the literature. The PALY was ascribed a financial value in terms of gross domestic product (GDP) per equivalent full-time worker. The total number of years lived, PALYs, and economic burden (in terms of GDP per PALY) were estimated. The model simulation was repeated assuming incidence was reduced, and the differences represented the impact of CHD prevention. All outcomes were discounted by 5% per annum. Over 10 years, the total projected years lived and PALYs in the Australian working-age population (with and without CHD) were 133 million and 83 million, respectively, amounting to A$17.2 trillion in GDP. We predicted more than 290 000 new (incident) CHD cases over the next 10 years. If all new cases of CHD could be prevented during this period, a total of 4 000 deaths could be averted, resulting in more than 8 000 years of life saved and 104 000 PALYs gained, equivalent to a gain of nearly A$21.8 billion (US$14.8 billion) in GDP., Conclusion: Prevention of CHD will prolong years of life lived and productive life years, resulting in substantial economic benefit. Policy makers and employers are encouraged to engage in preventive measures addressing CHD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background and Objectives: Frailty is a dynamic process with potential transitions over time. However, there is limited understanding of the patterns of frailty improvement. We conducted a systematic review and meta-analysis to estimate the natural rate of frailty regression among community-dwelling older adults aged at least 60 years., Research Design and Methods: Systematic searches for studies reporting frailty improvement were performed in 5 databases (Medline, Embase, CINAHL plus, Web of Science, and PsycINFO) from inception until January 2019., Results: Twenty-five studies from 26 countries were included. Among a baseline population of more than 50,000 individuals, the pooled prevalence of pre-frailty and frailty was 50.5% (95% confidence interval [CI] 47.8-53.3) and 12.8% (95% CI 9.1-17.0), respectively. During a median follow-up of 3.0 (range 1-10.0) years, 23.3% of surviving pre-frail individuals regressed to a robust state and 35.2% of surviving frail individuals reversed to a pre-frail or robust state. The pooled remission rates among people with pre-frailty and frailty were 80.4 (95% CI 61.7-104.6) and 135.3 (95% CI 98.1-186.5) per 1,000 person-years, respectively. Frailty and pre-frailty improvement rates varied by sex, diagnostic criteria, study region, and follow-up duration. The remission rates were significantly reduced when accounting for progressions to death. The heterogeneity of included studies was high which reflected considerable differences in methodological approach., Discussion and Implications: Although frailty is highly prevalent in older people, natural remission is possible and common. Improved understanding of the factors that confer increased likelihood of frailty regression may support the design of interventions to reduce the burden of frailty., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Peripheral artery disease affects 1.2% of the population globally and is associated with an increased risk of atherothrombotic cardiovascular events, major adverse limb events and mortality. The Cardiovascular Outcomes for People Using Anti-coagulation Strategies (COMPASS) trial demonstrated positive results of rivaroxaban plus aspirin therapy compared to aspirin therapy alone in those with peripheral artery disease or carotid artery disease. We sought to estimate the cost-effectiveness from the Australian healthcare system perspective., Methods and Results: A Markov model was developed to simulate the experiences of a hypothetical population of 1000 individuals with peripheral artery disease or carotid artery disease, profiled on the COMPASS trial, treated with rivaroxaban plus aspirin therapy versus aspirin therapy alone. With each annual cycle, individuals were at risk of having non-fatal cardiovascular disease events, major adverse limb events, or dying. Individuals were also at risk of non-fatal major bleeding. The model had a lifetime time horizon. Costs and utilities were sourced from the literature and discounted at 5.0% annually. Rivaroxaban plus aspirin therapy prevented 143 non-fatal cardiovascular disease events, 118 major adverse limb events and 10 deaths compared to aspirin therapy alone. Conversely, 156 additional major non-fatal bleeds were accrued. With an additional 256 quality-adjusted life years gained, at an additional cost of AUD$6,858,103, the incremental cost-effectiveness ratio was AUD$26,769 (discounted) per quality-adjusted life year gained, which is below Australia's arbitrary willingness to pay threshold of AUD$50,000., Conclusion: In those with peripheral artery disease or carotid artery disease, rivaroxaban plus aspirin therapy is effective and cost-effective in the prevention of recurrent cardiovascular disease compared to aspirin therapy alone.

Aims: The suitability of percutaneous coronary intervention (PCI), compared with coronary artery bypass grafting (CABG), for patients with complex multivessel coronary artery disease (MVCAD) remains a contentious topic. While the body of evidence regarding the clinical effectiveness of these revascularization strategies is growing, there is limited evidence concerning their long-term cost-effectiveness. We aim to critically appraise the body of literature investigating the cost-effectiveness of CABG compared with PCI using stents, and to assess the quality of the economic evidence available., Methods and Results: A systematic review was performed across six electronic databases; Medline, Embase, the NHS Economic Evaluation Database, the Database of Abstracts of Reviews of Effects, the health technology assessment database, and the Cochrane Library. All studies comparing economic attractiveness of CABG vs. PCI using bare-metal stents (BMS) or drug-eluting stents (DES) in balanced groups of patients were considered. Sixteen studies were included. These comprised studies of conventional CABG vs. BMS (n = 8), or DES (n = 4); off-pump CABG vs. BMS (n = 2), or DES (n = 1); and minimally invasive direct CABG vs. BMS (n = 2). The majority adopted a healthcare payer perspective (n = 14). The incremental cost-effectiveness ratios (ICERs) reported across studies varied widely according to perspective and time horizon. Favourable lifetime ICERs were reported for CABG in three trials. For patients with left main coronary artery disease, however, DES was reported as the dominant (more effective and cost-saving) strategy in one study., Conclusion: Overall, CABG rather than PCI was the favoured cost-effective treatment for complex MVCAD in the long term. While the evidence base for the cost-effectiveness of DES compared with CABG is growing, there is a need for more evaluations adopting a societal perspective, and time horizons of a lifetime or 10 or more years.

Background: The treatment of patients with metastatic melanomas that harbour BRAF V600E or V600K mutations with trametinib plus dabrafenib appears to be superior to treatment with vemurafenib alone. This treatment regimen is likely to become available in Switzerland in the near future., Objectives: To determine the cost-effectiveness of trametinib plus dabrafenib., Methods: A Markov cohort simulation was conducted to model the clinical course of typical patients with metastatic melanoma. Information on response rates, clinical condition and follow-up treatments were derived and transition probabilities estimated based on the results of a clinical trial that compared treatment with trametinib plus dabrafenib vs. vemurafenib alone., Results: Treatment with trametinib plus dabrafenib was estimated to cost an additional CHF199 647 (Swiss francs) on average and yield a gain of 0·52 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of CHF385 603 per QALY. Probabilistic sensitivity analyses showed that a willingness-to-pay threshold of CHF100 000 per QALY would not be reached at the current US price of trametinib., Conclusions: The introduction of trametinib in Switzerland at US market prices for the treatment of metastatic BRAF V600-mutated melanoma with trametinib plus dabrafenib is unlikely to be cost-effective compared with vemurafenib monotherapy. A reduction in the total price of the combination therapy is required to achieve an acceptable cost-effectiveness ratio for this clinically promising treatment., (© 2015 British Association of Dermatologists.)

Objective: To determine the cost-effectiveness of apixaban versus warfarin in patients with atrial fibrillation (AF) with a moderate to severe risk of stroke, from an Australian government-perspective., Methods: A decision-analytic Markov model was constructed to assess the cost-effectiveness of apixaban versus warfarin, based on data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in AF (ARISTOTLE) trial. The model comprised five health states: 'Alive, no major bleeding or stroke', 'Alive, no major bleeding, post stroke/systemic embolism', 'Alive, post major bleeding, no stroke', 'Alive, post-major bleeding and stroke' and 'Dead'. Disease cost data was derived from the North-East Melbourne Stroke Incidence Study and the Australian Refined Diagnose Related Groups. Costs of medications were based on data from the Pharmaceutical Benefit Scheme. Utility data was derived from published sources, and an annual discount rate of 5% was applied to costs and benefits. The main outcome of interest was incremental cost-effectiveness ratios per life year gained (LYG) and quality adjusted life years (QALYs) gained., Results: Over 20 years, in the sample of 1000 subjects the model predicted that compared to warfarin, apixaban led to a (discounted) of 0.33 LYG and 0.31 QALYs gained, at a net cost of $4,308 per-person. These equated to ICERs of $AUD12, 914 per LYG and $AUD13, 679 per QALY gained. Probabilistic sensitivity analysis demonstrated that apixaban was cost-effective at 99.0% probability using willingness to pay thresholds of $AUD45 000 per LYG and QALY., Conclusion: Compared to warfarin, apixaban is likely to represent a cost-effective means of preventing stroke-related morbidity and mortality in patients with AF., (© The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Cardiovascular disease (CVD) risk-prediction algorithms are key in determining one's eligibility for prevention strategies, but are often population-specific. Metabolic syndrome (MetS), a clustering of risk factors that increase the risk of CVD, does not currently have a risk-prediction algorithm available for prediction of CVD. The aim of this study was to compare the predictive capacities of an algorithm intended for 'healthy' individuals and one intended for 'diabetic' individuals., Methods: Individual-specific data from 2700 subjects defined as MetS but free of diagnosed CVD from the Australian Diabetes, Obesity and Lifestyle study was used to estimate 5-year risk of CVD using the two algorithms, and compared using Wilcoxon-signed rank test. CVD end point data was used to assess the performance using discrimination and calibration techniques of the two algorithms., Results: Five-year risk-prediction comparisons demonstrated that the UKPDS algorithm overpredicted risk in the younger age groups (25-54 years) and underpredicted risk in the older age groups (≥55 years) compared to the Framingham algorithm. A total of 133 CVD events occurred over a median follow up of 5.0 years. Model performance analyses demonstrated both the Framingham and UKPDS algorithms were poor at discrimination (area under receiver operator curve 0.513 and 0.524, respectively) and calibration (Hosmer-Lemeshow 467.1 and 297.0, respectively)., Conclusions: Neither the Framingham or UKPDS algorithms are ideal for prediction of CVD risk in a MetS population. This study highlights the need for development of population-specific risk-prediction algorithms for this growing population group.

Background: We sought to determine the incidence of newly diagnosed diabetes in treated elderly hypertensive patients and the prognostic impact of diabetes on long-term survival., Methods: The Second Australian National Blood Pressure (ANBP2) study randomized 6,083 hypertensive patients aged 65-84 years to angiotensin-converting enzyme inhibitor (ACEI) or thiazide diuretic-based therapy and followed them for a median of 4.1 years. Long-term survival was determined in 5,678 patients over an additional median of 6.9 years after ANBP2 (post-trial)., Results: After ANBP2, the cohort was classified into preexisting (7.2%), newly diagnosed (5.6%), and no diabetes (87.2%) groups. A 44% higher incidence of newly diagnosed diabetes was observed in patients randomized to thiazide diuretic compared with ACEI-based treatment. The other predictors of newly diagnosed diabetes were having a higher body mass index, having a higher random blood glucose, and living in a regional location compared to major cities (a geographical classification based on accessibility) at study entry. After completion of ANBP2, compared with those with no diabetes, the preexisting diabetes group experienced higher cardiovascular (hazards ratio (HR) = 1.65; 95% confidence interval (CI) = 1.03-2.65) and all-cause mortality (HR = 1.40; 95% CI = 1.02-1.92) when adjusted for age, sex, and treatment. A similar pattern was observed after including the post-trial period for cardiovascular (HR = 1.52; 95% CI = 1.20-1.93) and all-cause mortality (HR = 1.50; 95% CI = 1.29-1.73). However, when the newly diagnosed group was compared with the no diabetes group, no significant difference was observed in cardiovascular (HR = 0.33; 95% CI = 0.11-1.05) or all-cause mortality (HR = 0.76; 95% CI = 0.47-1.23) either during the ANBP2 trial or including post-trial follow-up (cardiovascular: HR = 0.82; 95% CI = 0.58-1.17; all-cause mortality: HR = 1.04; 95% CI = 0.85-1.27)., Conclusions: Long-term presence of diabetes reduces survival. Compared with thiazide diuretics, ACEI-based antihypertensives may delay the development of diabetes in those at risk and thus potentially improve cardiovascular outcome in the elderly.

Background: No population-based studies have investigated how the impact of hip and knee joint disease may vary with increasing severity., Objective: The purpose of this study was to evaluate health-related quality of life (HRQoL), work status, and health service utilization and costs according to severity of hip and knee joint disease., Design: A national cross-sectional survey was conducted., Methods: Five thousand individuals were randomly selected from the Australian electoral roll and invited to complete a questionnaire to screen for doctor-diagnosed hip arthritis, hip osteoarthritis (OA), knee arthritis, and knee OA. Severity was classified by means of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (range=0-100): <7=asymptomatic, 7-38=mild-moderate, and ≥39=severe. Health-related quality of life was evaluated by means of the Assessment of Quality of Life (AQoL) instrument (range=-0.04 to 1.00; scored worst-best). Self-reported data on work status and health service utilization were collected, with health care costs estimated with the use of government data., Results: Data were available for 1,157 participants, with 237 (20%) reporting hip or knee joint disease. Of these, 16% (n=37) were classified as asymptomatic, 51% (n=120) as mild-moderate, and 27% (n=64) as severe. The severe group reported very low HRQoL (adjusted mean AQoL=0.43, 95% confidence interval [95% CI]=0.38-0.47) compared with the mild-moderate group (adjusted mean AQoL=0.72, 95% CI=0.69-0.75) and the asymptomatic group (adjusted mean AQoL=0.80, 95% CI=0.74-0.86). Compared with the asymptomatic group, the severe group was >3 times less likely to undertake paid work (adjusted odds ratio=0.28, 95% CI=0.09-0.88) and >4 times less likely to undertake unpaid work (adjusted odds ratio=0.24, 95% CI=0.10-0.62). Although physical therapy services were used infrequently, primary and specialist care utilization and costs were highest for the severe group., Limitations: Other costs (including physical therapy consultations) were unavailable., Conclusions: A clear pattern of worsening HRQoL, reduced work participation, and higher medical care utilization was seen with increasing severity of joint disease.