The cost-effectiveness of coronary calcium score-guided statin therapy initiation for Australians with family histories of premature coronary artery disease.

OBJECTIVES: To compare the cost-effectiveness of coronary artery calcium (CAC) score-guided statin therapy criteria and American College of Cardiology/American Heart Association (ACC/AHA) guidelines (10-year pooled cohort equation [PCE] risk ≥ 7.5%) with selection according to Australian guidelines (5-year absolute cardiovascular disease risk [ACVDR] ≥ 10%), for people with family histories of premature coronary artery disease. STUDY DESIGN, SETTING: Markov microsimulation state transition model based on data from the Coronary Artery calcium score: Use to Guide management of Hereditary Coronary Artery Disease (CAUGHT-CAD) trial and transition probabilities derived from published statin prescribing and adherence outcomes and clinical data. PARTICIPANTS: 1083 people with family histories of premature coronary artery disease but no symptomatic cardiovascular disease. MAIN OUTCOME MEASURES: Relative cost-effectiveness over fifteen years, from the perspective of the Australian health care system, compared with usual care (Australian guidelines), assessed as incremental cost-effectiveness ratios (ICERs), with a notional willingness-to-pay threshold of $50 000 per quality-adjusted life-year (QALY) gained. RESULTS: Applying the Australian guidelines, 77 people were eligible for statin therapy (7.1%); with ACVDR 5-year risk ≥ 2% and CAC score > 0, 496 people (46%); with ACVDR 5-year risk ≥ 2% and CAC score ≥ 100, 155 people (14%); and with the ACC/AHA guidelines, 256 people (24%). The ICERs for CAC-guided selection were $33 108 (CAC ≥ 100) and $53 028 per QALY gained (CAC > 0); the ACC/AHA guidelines approach (ICER, $909 241 per QALY gained) was not cost-effective. CAC score-guided selection (CAC ≥ 100) was cost-effective for people with 5-year ACVDR of at least 5%. CONCLUSION: Expanding the number of people at low to intermediate CVD risk eligible for statin therapy should selectively target people with subclinical atherosclerosis identified by CAC screening. This approach can be more cost-effective than simply lowering treatment eligibility thresholds.

An economic case for a cardiovascular polypill? A cost analysis of the Kanyini GAP trial.

OBJECTIVE: To measure the costs of a polypill strategy and compare them with those of usual care in people with established cardiovascular disease (CVD) or at similarly high cardiovascular risk. DESIGN: A within-trial cost analysis of polypill-based care versus usual care with separate medications, using data from the Kanyini Guidelines Adherence with the Polypill (GAP) trial and linked health service and medication administrative claims data. PARTICIPANTS: Kanyini GAP participants who consented to Australian Medicare record access. MAIN OUTCOME MEASURES: Mean health service and pharmaceutical expenditure per patient per year, estimated with generalised linear models. Costs during the trial (randomisation January 2010 - May 2012, median follow-up 19 months, maximum follow-up 36 months) were inflated to 2012 costs. RESULTS: Our analysis showed a statistically significantly lower mean pharmaceutical expenditure of $989 (95% CI, $648-$1331) per patient per year in the polypill arm compared with usual care (P < 0.001; adjusted, excluding polypill cost). No significant difference was shown in health service expenditure. CONCLUSIONS: This study provides evidence of significant cost savings to the taxpayer and Australian Government through the introduction of a CVD polypill strategy. The savings will be less now than during the trial due to subsequent reductions in the costs of usual care. Nonetheless, given the prevalence of CVD in Australia, the introduction of this polypill could increase considerably the efficiency of health care expenditure in Australia. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN126080005833347.

Access to cardiac rehabilitation does not equate to attendance.

BACKGROUND/AIMS: Timely access to appropriate cardiac care is critical for optimizing positive outcomes after a cardiac event. Attendance at cardiac rehabilitation (CR) remains less than optimal (10%-30%). Our aim was to derive an objective, comparable, geographic measure reflecting access to cardiac services after a cardiac event in Australia. METHODS: An expert panel defined a single patient care pathway and a hierarchy of the minimum health services for CR and secondary prevention. Using geographic information systems a numeric/alpha index was modelled to describe access before and after a cardiac event. The aftercare phase was modelled into five alphabetical categories: from category A (access to medical service, pharmacy, CR, pathology within 1 h) to category E (no services available within 1 h). RESULTS: Approximately 96% or 19 million people lived within 1 h of the four basic services to support CR and secondary prevention, including 96% of older Australians and 75% of the indigenous population. Conversely, 14% (64,000) indigenous people resided in population locations that had poor access to health services that support CR after a cardiac event. CONCLUSION: Results demonstrated that the majority of Australians had excellent 'geographic' access to services to support CR and secondary prevention. Therefore, it appears that it is not the distance to services that affects attendance. Our 'geographic' lens has identified that more research on socioeconomic, sociological or psychological aspects to attendance is needed.

Semiparametric methods for multistate survival models in randomised trials.

Transform methods have proved effective for networks describing a progression of events. In semi-Markov networks, we calculated the transform of time to a terminating event from corresponding transforms of intermediate steps. Saddlepoint inversion then provided survival and hazard functions, which integrated, and fully utilised, the network data. However, the presence of censored data introduces significant difficulties for these methods. Many participants in controlled trials commonly remain event-free at study completion, a consequence of the limited period of follow-up specified in the trial design. Transforms are not estimable using nonparametric methods in states with survival truncated by end-of-study censoring. We propose the use of parametric models specifying residual survival to next event. As a simple approach to extrapolation with competing alternative states, we imposed a proportional incidence (constant relative hazard) assumption beyond the range of study data. No proportional hazards assumptions are necessary for inferences concerning time to endpoint; indeed, estimation of survival and hazard functions can proceed in a single study arm. We demonstrate feasibility and efficiency of transform inversion in a large randomised controlled trial of cholesterol-lowering therapy, the Long-Term Intervention with Pravastatin in Ischaemic Disease study. Transform inversion integrates information available in components of multistate models: estimates of transition probabilities and empirical survival distributions. As a by-product, it provides some ability to forecast survival and hazard functions forward, beyond the time horizon of available follow-up. Functionals of survival and hazard functions provide inference, which proves sharper than that of log-rank and related methods for survival comparisons ignoring intermediate events.

Assessment of cardiovascular disease risk in South asian populations.

Although South Asian populations have high cardiovascular disease (CVD) burden in the world, their patterns of individual CVD risk factors have not been fully studied. None of the available algorithms/scores to assess CVD risk have originated from these populations. To explore the relevance of CVD risk scores for these populations, literature search and qualitative synthesis of available evidence were performed. South Asians usually have higher levels of both "classical" and nontraditional CVD risk factors and experience these at a younger age. There are marked variations in risk profiles between South Asian populations. More than 100 risk algorithms are currently available, with varying risk factors. However, no available algorithm has included all important risk factors that underlie CVD in these populations. The future challenge is either to appropriately calibrate current risk algorithms or ideally to develop new risk algorithms that include variables that provide an accurate estimate of CVD risk.

Validation of de-identified record linkage to ascertain hospital admissions in a cohort study.

BACKGROUND: Cohort studies can provide valuable evidence of cause and effect relationships but are subject to loss of participants over time, limiting the validity of findings. Computerised record linkage offers a passive and ongoing method of obtaining health outcomes from existing routinely collected data sources. However, the quality of record linkage is reliant upon the availability and accuracy of common identifying variables. We sought to develop and validate a method for linking a cohort study to a state-wide hospital admissions dataset with limited availability of unique identifying variables. METHODS: A sample of 2000 participants from a cohort study (n = 41 514) was linked to a state-wide hospitalisations dataset in Victoria, Australia using the national health insurance (Medicare) number and demographic data as identifying variables. Availability of the health insurance number was limited in both datasets; therefore linkage was undertaken both with and without use of this number and agreement tested between both algorithms. Sensitivity was calculated for a sub-sample of 101 participants with a hospital admission confirmed by medical record review. RESULTS: Of the 2000 study participants, 85% were found to have a record in the hospitalisations dataset when the national health insurance number and sex were used as linkage variables and 92% when demographic details only were used. When agreement between the two methods was tested the disagreement fraction was 9%, mainly due to "false positive" links when demographic details only were used. A final algorithm that used multiple combinations of identifying variables resulted in a match proportion of 87%. Sensitivity of this final linkage was 95%. CONCLUSIONS: High quality record linkage of cohort data with a hospitalisations dataset that has limited identifiers can be achieved using combinations of a national health insurance number and demographic data as identifying variables.

AUSDRISK: an Australian Type 2 Diabetes Risk Assessment Tool based on demographic, lifestyle and simple anthropometric measures.

OBJECTIVE: To develop and validate a diabetes risk assessment tool for Australia based on demographic, lifestyle and simple anthropometric measures. DESIGN AND SETTING: 5-year follow-up (2004-2005) of the Australian Diabetes, Obesity and Lifestyle study (AusDiab, 1999-2000). PARTICIPANTS: 6060 AusDiab participants aged 25 years or older who did not have diagnosed diabetes at baseline. MAIN OUTCOME MEASURES: Incident diabetes at follow-up was defined by treatment with insulin or oral hypoglycaemic agents or by fasting plasma glucose level > or = 7.0 mmol/L or 2-hour plasma glucose level in an oral glucose tolerance test > or = 11.1 mmol/L. The risk prediction model was developed using logistic regression and converted to a simple score, which was then validated in two independent Australian cohorts (the Blue Mountains Eye Study and the North West Adelaide Health Study) using the area under the receiver operating characteristic curve (AROC) and the Hosmer-Lemeshow (HL) chi(2) statistic. RESULTS: 362 people developed diabetes. Age, sex, ethnicity, parental history of diabetes, history of high blood glucose level, use of antihypertensive medications, smoking, physical inactivity and waist circumference were included in the final prediction model. The AROC of the diabetes risk tool was 0.78 (95% CI, 0.76-0.81) and HL chi(2) statistic was 4.1 (P = 0.85). Using a score > or = 12 (maximum, 35), the sensitivity, specificity and positive predictive value for identifying incident diabetes were 74.0%, 67.7% and 12.7%, respectively. The AROC and HL chi(2) statistic in the two independent validation cohorts were 0.66 (95% CI, 0.60-0.71) and 9.2 (P = 0.32), and 0.79 (95% CI, 0.72-0.86) and 29.4 (P < 0.001), respectively. CONCLUSIONS: This diabetes risk assessment tool provides a simple, non-invasive method to identify Australian adults at high risk of type 2 diabetes who might benefit from interventions to prevent or delay its onset.

Recalibration and validation of the SCORE risk chart in the Australian population: the AusSCORE chart.

BACKGROUND: Development of a validated risk prediction model for future cardiovascular disease (CVD) in Australians is a high priority for cardiovascular health strategies. DESIGN: Recalibration of the SCORE (Systematic COronary Risk Evaluation) risk chart based on Australian national mortality data and average major CVD risk factor levels. METHODS: Australian national mortality data (2003-2005) were used to estimate 10-year cumulative CVD mortality rates for people aged 40-74 years. Average age-specific and sex-specific levels of systolic blood pressure, total cholesterol and prevalence of current smoking were generated from data obtained in eight Australian large-scale population-based surveys undertaken from the late 1980s. The SCORE risk chart was then recalibrated by applying hazard ratios for 10-year CVD mortality obtained in the SCORE project. Discrimination and calibration of the recalibrated model was evaluated and compared with that of the original SCORE and Framingham equations in the Blue Mountains Eye Study in Australia using Harrell's c and Hosmer-Lemeshow chi statistics, respectively. RESULTS: An Australian risk prediction chart for CVD mortality was derived. Among 1998 Blue Mountains Eye Study participants aged 49-74 years with neither CVD nor diabetes at baseline, the Harrell's c statistics for the Australian risk prediction chart for CVD mortality were 0.76 (95% confidence interval: 0.69-0.84) and 0.71 (confidence interval: 0.62-0.80) in men and women, respectively. The corresponding Hosmer-Lemeshow chi statistics, the measure of calibration, were 2.32 (P = 0.68) and 7.43 (P = 0.11), which were superior to both the SCORE and Framingham equations. CONCLUSION: This new tool provides a valid and reliable method to predict risk of CVD mortality in the general Australian population.

Where on the healthcare continuum should we invest? The case for primary care?

Cardiovascular diseases and particularly coronary heart disease are associated with the major personal and economic health burden in Australia. They are also the major cause of health inequalities. The associated economic burden is projected to increase markedly with ageing of the population and decrease in case-fatality rates with acute events such as myocardial infarction. Prevention has recently been listed second among the priorities of the newly formed National Health and Hospitals Reform Commission. It is logical that strategies to prevent CVD events should impact across the healthcare continuum. These should include population-wide measures to counter the epidemic of overweight, targeted cost-effective approaches to high-risk asymptomatic individuals, more effective management of acute events and systems of care to support implementation of evidence-based secondary prevention therapies. Recent cost-utility analyses support the proposition that the general practice environment should be a particular focus for CHD primary and secondary prevention approaches.

Rationale and design of the Home Automatic External Defibrillator Trial (HAT).

Most cardiac arrests occur in the home, where emergency medical services (EMS) systems are challenged to provide timely care. Because a large proportion of sudden cardiac arrests (SCAs) are due to ventricular tachycardia or ventricular fibrillation, home use of an automated external defibrillator (AED) might offer an opportunity to decrease mortality in those at risk. Predicting who will have a cardiac arrest in the general population is difficult. Individuals at high risk are usually easily identified and may become candidates for implantable cardioverter defibrillators. It is within the population at lower risk where home AEDs may be most useful. The purpose of the Home Automatic External Defibrillator Trial (HAT) is to test whether providing home access to an AED can improve survival in patients at modest risk of SCA, such as those surviving an anterior myocardial infarction but in whom implantable cardioverter defibrillator therapy is not deemed necessary. Between January 23, 2003, and October 20, 2005, 7001 patients were enrolled, with completion of follow-up scheduled for September 30, 2007. Randomization was conducted in a 1:1 fashion between control therapy, comprising the standard lay response to SCA (calling the EMS and performing cardiopulmonary resuscitation), and the use of an AED first, followed by calling the EMS and performing cardiopulmonary resuscitation. The primary end point is all-cause mortality. Secondary outcomes include survival from SCA (witnessed and unwitnessed, in home and out of home), incremental cost-effectiveness, and quality of life measures for both the patient and the spouse/companion. The results of the trial should be available in mid 2008.

Differences in cardiovascular mortality between Australia and New Zealand according to socioeconomic status: findings from the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study.

BACKGROUND: Cardiovascular mortality is higher in New Zealand compared to Australia, but reasons for this difference are uncertain. This study describes differences in cardiovascular risk factors and cardiovascular mortality in Australians and New Zealanders with stable coronary artery disease stratified by socioeconomic status. METHODS: Socioeconomic status was estimated from the residential area of 5949 Australians and 2784 New Zealanders with a history of myocardial infarction or unstable angina who participated in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study. Socioeconomic and international differences in cardiovascular risk factors, medical treatments, and cardiovascular mortality during a median follow-up period of 7.8 years were evaluated. RESULTS: Cardiovascular mortality increased as the median residential-area income decreased in both Australia (hazard ratio [HR]/income tertile 1.20, 95% confidence interval [CI] 1.08-1.32) and New Zealand (HR 1.16, 95%CI 1.02-1.31), but was higher in New Zealand across all socioeconomic groups (HR 1.42, 95%CI 1.25-1.61). Obesity, smoking, and a high white blood cell count at baseline were associated with higher cardiovascular mortality and were more common in lower-income areas in both countries. The total:HDL cholesterol ratio was higher in New Zealand, but similar across all socioeconomic groups. In both countries there were socioeconomic gradients in open-label usage of cholesterol-lowering medication, percutaneous coronary intervention, and coronary artery bypass surgery. However, Australians in all socioeconomic groups were more likely than New Zealanders to receive these treatments. CONCLUSIONS: Although there is an important socioeconomic gradient in cardiovascular mortality in both Australia and New Zealand, cardiovascular mortality is higher in New Zealanders than Australians with stable coronary disease from all socioeconomic groups.

Cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with previous acute coronary syndromes aged 65 to 74 years compared with younger patients: results from the LIPID study.

BACKGROUND: We compared cost-effectiveness of pravastatin in a placebo-controlled trial in 5500 younger (31-64 years) and 3514 older patients (65-74 years) with previous acute coronary syndromes. METHODS: Hospitalizations and long-term medication within the 6 years of the trial were estimated in all patients . Drug dosage, nursing home, and ambulatory care costs were estimated from substudies. Incremental costs per life saved of pravastatin relative to placebo were estimated from treatment effects and resource use. RESULTS: Over 6 years, pravastatin reduced all-cause mortality by 4.3% in the older patients and by 2.3% in the younger patients. Older patients assigned pravastatin had marginally lower cost of pravastatin and other medication over 6 years (A dollar 4442 vs A dollar 4637), but greater cost offsets (A dollar 2061 vs A dollar 897) from lower rates of hospitalizations. The incremental cost per life saved with pravastatin was A dollar 55500 in the old and A dollar 167200 in the young. Assuming no treatment effect beyond the study period, the life expectancy to age 82 years of additional survivors was 9.1 years in the older and 17.3 years in the younger. Estimated additional life-years saved from pravastatin therapy were 0.39 years for older and 0.40 years for younger patients. Incremental costs per life-year saved were A dollar 7581 in the older and A dollar 14944 in the younger, if discounted at 5% per annum. CONCLUSIONS: Pravastatin therapy was more cost-effective among older than younger patients, because of their higher baseline risk and greater cost offsets, despite their shorter life expectancy.

Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?

OBJECTIVE: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels. DESIGN: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo. PATIENTS AND SETTING: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992. MAIN OUTCOME MEASURES: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life. RESULTS: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107 730 (95% CI, $68 626-$209 881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%). CONCLUSIONS: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.