Conceived and designed the experiments: TV SL RC LC JB. Performed the experiments: LC AM. Analyzed the data: LC TV AM. Wrote the paper: LC TV. Designed the model used in analysis: SL TV.
The authors have declared that no competing interests exist.
Despite many decades of declining mortality rates in the Western world, cardiovascular disease remains the leading cause of death worldwide. In this research we evaluate the optimal mix of lifestyle, pharmaceutical and population-wide interventions for primary prevention of cardiovascular disease.
In a discrete time Markov model we simulate the ischaemic heart disease and stroke outcomes and cost impacts of intervention over the lifetime of all Australian men and women, aged 35 to 84 years, who have never experienced a heart disease or stroke event. Best value for money is achieved by mandating moderate limits on salt in the manufacture of bread, margarine and cereal. A combination of diuretic, calcium channel blocker, ACE inhibitor and low-cost statin, for everyone with at least 5% five-year risk of cardiovascular disease, is also cost-effective, but lifestyle interventions aiming to change risky dietary and exercise behaviours are extremely poor value for money and have little population health benefit.
There is huge potential for improving efficiency in cardiovascular disease prevention in Australia. A tougher approach from Government to mandating limits on salt in processed foods and reducing excessive statin prices, and a shift away from lifestyle counselling to more efficient absolute risk-based prescription of preventive drugs, could cut health care costs while improving population health.
Despite many decades of declining mortality rates in the Western world
Many countries have already developed guidelines and implemented interventions for primary prevention of CVD. Most guidelines recommend lifestyle behaviour-change approaches as a first line strategy, with blood pressure-lowering and/or cholesterol drugs for those at highest risk
With rising health care costs, it is vital that countries combine intervention strategies that will achieve maximum improvement in cardiovascular health at lowest cost to the health sector. Cost-effectiveness analyses for the WHO-CHOICE program in 2000, showed that a combination of beta-blocker, diuretic, statin and aspirin could be cost-effective, if provided to everyone with at least a 5% probability of a cardiovascular event in the next ten years, in regions with low child and adult mortality (e.g. UK, US and Australia)
Australia is currently re-visiting its guidelines for primary prevention of cardiovascular disease. In this research we evaluate the optimal mix of lifestyle, pharmaceutical and population-wide interventions from an Australian health sector perspective. We also evaluate the current practice of blood pressure and cholesterol intervention in Australia, and examine this against the optimal mix, to quantify the potential for improving population health and reducing health sector expenditure.
The study was approved by the Behavioural & Social Sciences Ethical Review Committee of the University of Queensland in accordance with the National Health and Medical Research Council guidelines (Clearance no. 2004000796). The study was based on analysis of publically available data. It did not involve human participants or require informed consent.
Intervention | Annual cost per person |
Measure of effect | Effect size | Sources |
Thiazide diuretic | $71 | RR IHD RR stroke | 0.86 (0.06) 0.62 (0.05) | |
Beta-blocker | $106 | RR IHD RR stroke | 0.89 (0.06) 0.83 (0.07) | |
Calcium channel blocker | $218 | RR IHD RR stroke | 0.85 (0.04) 0.66 (0.04) | |
ACE inhibitor | $212 | RR IHD RR stroke | 0.83 (0.03) 0.78 (0.07) | |
Aspirin | $40 | RR IHD RR stroke (isch.) RR stroke (haem.) RR GI bleed | 0.82 (0.04) 0.86 (0.07)1.32 (0.19) 1.54 (0.13) | |
Statin | Aust.: $687 NZ: $19 | RR IHD RR stroke | 0.70 (0.05) 0.81 (0.06) | |
Phytosterol margarine | $258 ($38) | Total cholesterol | 7.5% (1.9%) | |
Dietary advice | Yr 1: $132 ($213) Yr 2+: $86 ($39) | Systolic BP Total cholesterol | 1.6% (0.4%) 3.1%(1.2%) | |
Lifestyle program | Yr 1: $257 ($152) Yr 2+: $172 ($58) | Systolic BP Total cholesterol | 2.6% (0.5%) 3.3%(0.6%) | |
Community heart health program | Yr 1: $2.37 ($0.47) Yr 2+:$1.60 ($0.32) | Systolic BP Total cholesterol | 2.5% (0.7%)−0.51% (0.6%) | |
Mandatory salt reduction | $0.81 ($0.08) | mgNa/day men mgNa/day women | 10.6 (0.74) 7.3 (0.53) | |
Voluntary salt reduction (current practice) | $0.49 ($0.05) | mgNa/day men mgNa/day women | 0.50 (0.03) 0.34 (0.02) | |
Lipid-lowering (current practice) | $683 | RR IHD RR stroke | 0.70 (0.05) 0.81 (0.06) | |
BP-lowering (current practice) | $170 | RR IHD RR stroke | 0.85 (0.04) 0.70 (0.05) |
NB. Values are mean and standard error, unless otherwise stated. BP – blood pressure; GP – general practitioner; NZ – New Zealand; RR – relative risk; IHD – ischaemic heart disease.
All costs are adjusted to 2008 Australian dollars using consumer price indices
Table A2 provides further detail of sources and assumptions underlying the measurement of intervention costs and effects.
We evaluate cost-effectiveness of interventions to prevent CVD in the 2008 Australian population of 35 to 84 year olds who have not previously experienced a CVD event (defined as angina, myocardial infarction or stroke). We include two interventions targeting the whole population, a community heart health program and mandatory reduction of salt in the manufacture of breads, margarines and cereals; six interventions targeting those at increased risk of disease with pharmacological agents, diuretics, ACE inhibitors, calcium channel blockers, beta-blockers, statins and aspirin; and three interventions targeting those at increased risk of disease with interventions to change behaviour, dietary advice from a doctor or dietitian, referral to a more intensive lifestyle program with specialised counselling, and advice from a doctor to switch to phytosterol-enriched margarine. We also model the current practice coverage of these interventions for primary prevention of CVD in Australia. Key components of current practice include voluntary (rather than mandatory) reduction of salt in breads, margarines and cereals; dietary advice from a general practitioner (GP); and blood pressure- and cholesterol-lowering drug therapies.
Two of the interventions, the community heart health program and reduction of salt in processed foods, are delivered to the whole population. We assume the average population effect of these interventions is sustained with ongoing delivery of the interventions.
All other interventions are delivered in primary care. We determine the annual number of 35 to 84 year olds visiting a GP from an Australian GP sample registration system
We determine the probability of an event using the Framingham risk prediction equation
Of those patients eligible to receive intervention, we assume that 40% will no longer be adherent after 12 months, based on rates of discontinuation with blood pressure-lowering and cholesterol-lowering therapies in Australia
The modelled measures of intervention costs and effects are summarised in
Drug costs are based on prices in Australia’s Pharmaceutical Benefits Scheme (PBS) list of tax-subsidised drugs
The cost of phytosterol-enriched margarine is derived from a price survey of all available products available at the two major Australian supermarket chains, assuming that each product contains the Australian standard concentration of plant sterols (82 g per kg of margarine
The cost of the community heart health program is based on the bottom-up costing of the Hartslag Limburg cardiovascular prevention project
The cost of the current voluntary program for salt reduction in breads, margarines and cereals is derived from the proportion of products participating in the current Heart Foundation program
Intervention and target group | Health gain of intervention when implemented individually (DALYs) |
Health gain of intervention when added to the package (DALYs) |
Mandatory salt limits (all risk levels) | 80,000 (60,000 to 100,000) | 80,000 (60,000 to 100,000) |
Diuretic (≥15% risk) | 39,000 (22,000 to 59,000) | 38,000 (22,000 to 58,000) |
Diuretic (10–14% risk) | 40,000 (23,000 to 61,000) | 39,000 (22,000 to 59,000) |
Diuretic (5–9% risk) | 77,000 (43,000 to 120,000) | 75,000 (42,000 to 110,000) |
Ca channel blocker (≥15% risk) | 37,000 (24,000 to 54,000) | 28,000 (18,000 to 41,000) |
Ca channel blocker (10–14% risk) | 39,000 (25,000 to 55,000) | 29,000 (18,000 to 42,000) |
ACE inhibitor (≥15% risk) | 31,000 (18,000 to 47,000) | 20,000 (12,000 to 30,000) |
Ca channel blocker (5–9% risk) | 74,000 (47,000 to 110,000) | 56,000 (34,000 to 81,000) |
ACE inhibitor (10–14% risk) | 32,000 (19,000 to 49,000) | 21,000 (13,000 to 31,000) |
ACE inhibitor (5–9% risk) | 62,000 (36,000 to 95,000) | 40,000 (24,000 to 61,000) |
Statin (≥15% risk) | 41,000 (24,000 to 62,000) | 25,000 (15,000 to 38,000) |
Comm. heart program (all risk levels) | 3,000 (1,500 to 4,700) | 2,600 (1,300 to 4,000) |
Statin (10–14% risk) | 43,000 (25,000 to 65,000) | 27,000 (16,000 to 40,000) |
Statin (5–9% risk) | 85,000 (50,000 to 130,000) | 51,000 (30,000 to 77,000) |
Dietary advice (≥15% risk) | 180 (110 to 280) | 82 (46 to 130) |
Dietary advice (10–14% risk) | 190 (110 to 290) | 86 (48 to 140) |
Dietary advice (5–9% risk) | 370 (210 to 580) | 160 (91 to 270) |
Phytosterol (≥15% risk) | 160 (82 to 260) | 80 (38 to 130) |
Phytosterol (10–14% risk) | 170 (86 to 270) | 84 (40 to 140) |
Phytosterol (5–9% risk) | 330 (170 to 540) | 160 (77 to 270) |
Aspirin (≥15% risk) | 19,000 (7,200 to 33,000) |
|
Aspirin (10–14% risk) | 20,000 (7,700 to 35,000) |
|
Aspirin (5–9% risk) | 39,000 (16,000 to 68,000) |
|
Beta-blocker (≥15% risk) | 21,000 (5,200 to 39,000) |
|
Beta-blocker (10–14% risk) | 22,000 (5,400 to 40,000) |
|
Beta-blocker (5–9% risk) | 42,000 (10,000 to 79,000) |
|
Lifestyle program (≥15% risk) | 250 (160 to 360) |
|
Lifestyle program (10–14% risk) | 270 (170 to 380) |
|
Lifestyle program (5–9% risk) | 520 (330 to 740) |
|
Values are mean and 95% uncertainty interval, rounded to two significant figures. DALY – Disability-adjusted life year.
Intervention not included in the optimal package because a more cost-effective alternative is available.
Intervention and target group | Cost-effectiveness of intervention when implemented individually ($/DALY) |
Cost-effectiveness of intervention when added to the package ($/DALY) |
Mandatory salt limits (all risk levels) | Dominant (Dominant to Dominant) | Dominant (Dominant to Dominant) |
Diuretic (≥15% risk) | Dominant (Dominant to $5,600) | Dominant (Dominant to $5,600) |
Diuretic (10–14% risk) | $2,000 (Dominant to $10,000) | $2,000 (Dominant to $10,000) |
Diuretic (5–9% risk) | $5,800 (Dominant to $16,000) | $5,800 (Dominant to $16,000) |
Ca channel blocker (≥15% risk) | $7,900 ($3,300 to $14,000) | $7,900 ($3,300 to $14,000) |
Ca channel blocker (10–14% risk) | $12,000 ($6,700 to $20,000) | $12,000 ($6,700 to $20,000) |
ACE inhibitor (≥15% risk) | $10,000 ($4,800 to $21,000) | $10,000 ($4,800 to $21,000) |
Ca channel blocker (5–9% risk) | $19,000 ($12,000 to $29,000) | $19,000 ($12,000 to $29,000) |
ACE inhibitor (10–14% risk) | $15,000 ($8,400 to $28,000) | $15,000 ($8,400 to $28,000) |
ACE inhibitor (5–9% risk) | $23,000 ($14,000 to $40,000) | $23,000 ($14,000 to $40,000) |
Statin (≥15% risk) | $28,000 ($18,000 to $46,000) | $28,000 ($18,000 to $46,000) |
Comm. heart program (all risk levels) | $44,000 ($19,000 to $100,000) | $44,000 ($19,000 to $100,000) |
Statin (10–14% risk) | $36,000 ($25,000 to $59,000) | $36,000 ($25,000 to $59,000) |
Statin (5–9% risk) | $51,000 ($37,000 to $81,000) | $51,000 ($37,000 to $81,000) |
Dietary advice (≥15% risk) | $1,000,000 ($610,000 to $2,400,000) | $1,000,000 ($610,000 to $2,400,000) |
Dietary advice (10–14% risk) | $1,100,000 ($730,000 to $3,000,000) | $1,100,000 ($730,000 to $3,000,000) |
Dietary advice (5–9% risk) | $1,400,000 ($920,000 to $3,900,000) | $1,400,000 ($920,000 to $3,900,000) |
Phytosterol (≥15% risk) | $3,200,000 ($1,900,000 to $5,900,000) | $3,200,000 ($1,900,000 to $5,900,000) |
Phytosterol (10–14% risk) | $3,900,000 ($2,400,000 to $7,300,000) | $3,900,000 ($2,400,000 to $7,300,000) |
Phytosterol (5–9% risk) | $4,900,000 ($3,000,000 to $9,300,000) | $4,900,000 ($3,000,000 to $9,300,000) |
Aspirin (≥15% risk) | $1,800 (Dominant to $18,000) |
|
Aspirin (10–14% risk) | $3,500 (Dominant to $24,000) |
|
Aspirin (5–9% risk) | $8,300 (Dominant to $34,000) |
|
Beta-blocker (≥15% risk) | $10,000 ($1,100 to $74,000) |
|
Beta-blocker (10–14% risk) | $15,000 ($3,300 to $94,000) |
|
Beta-blocker (5–9% risk) | $22,000 ($7,700 to $130,000) |
|
Lifestyle program (≥15% risk) | $1,400,000 ($960,000 to $2,500,000) |
|
Lifestyle program (10–14% risk) | $1,600,000 ($1,100,000 to $3,200,000) |
|
Lifestyle program (5–9% risk) | $2,100,000 ($1,400,000 to $4,100,000) |
|
Cost-effectiveness ratios are median and 95% uncertainty interval, rounded to two significant figures. Where the ratio is
Intervention not included in the optimal package because a more cost-effective alternative is available.
The costs of dietary advice from a GP or dietitian and costs of participation in a lifestyle program are based on Australian Government costs for GP
Measures of intervention efficacy are based on meta-analyses of relevant randomised controlled trials, with the exception of voluntary and mandatory salt reduction, where program effectiveness is determined from a New Zealand study of the sodium reduction program
Addition of the interventions that are not visible on the graph, is not optimal until much higher cost-effectiveness thresholds (dietary advice above $2.4 million/DALY and phytosterol margarine above $6.7 million/DALY).
Interventions are added to the mix in order of cost-effectiveness, thus the pathway reflects the efficiency frontier. The pathway is shown as a solid line where the incremental cost-effectiveness of adding an intervention to the mix is under the cost-effectiveness threshold of $50,000/DALY, and shown as a dashed line where the addition of the next intervention is not cost-effectiveness (i.e. it exceeds the threshold of $50,000/DALY).
Current practice | Cost-effective package |
Cost-effective package |
|
|
190 (140 to 240) | 430 (310 to 570) | 530 (370 to 710) |
|
$7.1 ($5.7 to $8.5) | $5.5 ($3.9 to $7.3) | $6.3 ($4.5 to $8.4) |
|
$1.6 ($1.3 to $1.9) | $2.0 ($1.4 to $2.7) | $2.1 ($1.5 to $2.9) |
|
−$2.2 (−$3.0 to −$1.5) | −$4.8 (−$6.9 to −$3.0) | −$6.1 (−$9.0 to −$3.8) |
|
$6.5 ($5.1 to $8.0) | $2.8 ($1.1 to $4.6) | $2.3 ($0.51 to $4.3) |
Cost-effective package includes population-wide mandatory limits on salt in breads, margarines and cereals, and a mix of diuretic, calcium channel blocker and ACE inhibitor drugs for everyone with at least 5% risk of a CVD event in the next five years.
Statins provided for everyone with at least 5% risk of a CVD event in the next five years, at an annual cost of $18.25 (equivalent to the current price in New Zealand).
Cost-effectiveness analysis is carried out using the ‘generalised cost-effectiveness analysis’ approach developed for the World Health Organisation
We use a discrete time Markov model to simulate costs and health outcomes for the population that is eligible for each intervention (or intervention combination), in five-year age and sex cohorts. The Markov model has four primary health states, with transition rates capturing probabilities of incidence and case fatality for fatal and non-fatal IHD and stroke events. Probabilities of gastrointestinal (GI) bleeds and hemorrhagic stroke are taken into account as side-effects of aspirin therapy. Rates are derived from Australian hospital and mortality databases
The total years of life lived by the population, both with and without intervention, are adjusted for time spent in ill health using utility or disability weights that capture the average quality of life or ‘disability’ experienced at each age and sex, with or without ischaemic heart disease, stroke or a GI bleed. This weighting process can be carried out using utility weights to derive quality-adjusted life years (QALYs), or using disability weights to derive the loss of health-related quality of life captured in disability-adjusted life years (DALYs). Although similar survey techniques are used to elicit health state preferences for both utility and disability weights, health state preferences for the QALY weights are typically elicited from surveys of patients or the general population while health state preferences for the DALY weights have been elicited from expert panels. A comparison of the utility and disability weights for ischaemic heart disease, stroke, GI bleeds and all other ‘background’ disability can be found in
Using Markov model predictions of the years of life lived and time spent in ill health, we simulate costs of treating IHD, stroke and GI bleed events. Annual costs in the initial year of illness and in subsequent years are determined from hospital in-patient costs
We simulate costs and health outcomes over time until everyone in the population has died. All future costs and health outcomes are discounted at a rate of 3%
Mandating more moderate use of salt in breads, margarines and cereals is easily the most effective (
Blood pressure-lowering with beta-blockers, although cost-effective, has a lower probability of improving population health than diuretic, calcium channel blocker and ACE inhibitor options, and would not be recommended in preference to these three readily available and cost-effective drugs. Aspirin, also cost-effective on average, has a much higher probability of causing harm than the other drugs evaluated; if other more cost-effective drugs are first provided, the potential health benefits of aspirin are reduced, and it is no longer a cost-effective strategy for primary prevention of CVD.
No other interventions represent good value for money (
The current practice combination of blood pressure-lowering drugs, statin drugs, dietary advice and voluntary participation of food manufacturers in limiting salt use in processed foods, is inefficient compared to the optimal approach of mandating more moderate use of salt and providing diuretics, calcium channel blockers and ACE inhibitors for everyone with at least 5% cardiovascular risk (
Reducing the costs of statin drugs would produce even greater benefits (
A number of factors influence the total costs and health gain of the optimal package of interventions, including discount rate, addition of other health care costs in added years of life, CVD trends and measurement of health in QALYs rather than DALYs, but these factors do not influence the order of interventions in the pathway (
To achieve best value for money in the primary prevention of CVD, the Australian government must take a tougher approach in mandating limits on salt in processed foods (bread, margarine and cereal), and fund a combination of diuretic, calcium channel blocker, ACE inhibitor and (low cost) statin drugs for everyone found to have at least a 5% five-year risk of CVD when visiting their local GP. If implemented in Australia, this package of interventions could achieve a three-fold improvement in current population health and reduce current lifetime health care expenditure by $4.2 billion (Australia’s total health care expenditure is around $100 billion annually
Our findings are robust to modelling assumptions around discount rate, inclusion of other non-CVD health care costs in added years of life, and choice of health metric (DALY versus QALY), but are sensitive to drug price. It is likely, therefore, that the Australian cost-effectiveness results will broadly reflect cost-effectiveness of primary prevention strategies in other countries with similar epidemiological and health system characteristics (e.g. United Kingdom and New Zealand), with the exception of the results on statin drugs. Australia currently pays around five times the average price paid for statin drugs in other OECD countries
Our results are broadly consistent with the results of previous analyses from WHO-CHOICE
While cost-effectiveness ratios for the individually-targeted lifestyle interventions were very unfavourable, our analyses do not capture any additional benefits from reduced smoking, increased physical activity, or other possible lifestyle changes, unlike with the analyses of drug interventions, where health benefits are entirely mediated by changes in modelled blood pressure or cholesterol. This means that we are likely underestimating the health benefits of the lifestyle interventions. We do find, however, that even if we add in the DALYs and treatment costs averted by lifestyle intervention changes in physical activity, fruit and vegetable intake, weight loss, alcohol intake and smoking, which have all been modelled separately in other comparable Australian analyses
The policy-makers behind England’s Vascular Check program should be concerned about the potentially poor value for money of the lifestyle behaviour-change interventions in Australia. The Vascular Check program was predicted to be highly cost-effective by England’s Department of Health
It is also important to evaluate the longer term outcomes of the lifestyle and other cardiovascular disease interventions. Trials of lifestyle interventions in particular are often short-term (e.g. less than two years follow-up). We have assumed that the effects (and costs) of these interventions will be sustained for those who continue to participate, but further evidence is needed to clarify the sustainability of different intervention approaches.
In Australia, it is vital that policy-makers recognise just how far away the country is from optimal prevention of CVD. The remedy is three-fold. The first step is to stand firm against industry pressure and redress current policies around statin dug pricing; this alone would produce immediate Government savings of $500 million in the first year. The second step is to address current inefficiencies in primary care. Australian GPs have been slow to adopt tools for absolute risk assessment
Cost-effectiveness model.
(DOC)
Model input data.
(DOC)
Cost-effectiveness sensitivity results.
(DOC)