|Resource implications and health benefits of primary prevention strategies for cardiovascular disease in people aged 30 to 74: mathematical modelling study
|Marshall T, Rouse A
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
Two groups of guidelines for the primary prevention of cardiovascular disease in people aged 30 to 74 years were studied. These were guidelines based on the joint British recommendations (JBR), and novel guidelines based on the authors' recommendations (Rouse-Marshall, RM).
The JBR guidelines included three levels of recommendations, JBR-1, JBR-2 and JBR-3. These were based on the assessment of all adults using the following steps:
assessment (assess cardiovascular risk of all patients five yearly),
criteria for antihypertensives (5-year coronary heart disease (CHD) risk greater than 7.5%, and blood pressure >160 mmHg systolic or >100 mmHg diastolic),
criteria for cholesterol-lowering treatment (5-year CHD risk greater than 7.5% and total cholesterol concentration >5 mmol/L),
criteria for aspirin treatment (age over 50 and 5-year CHD risk greater than 7.5%), and
the long-term management of patients receiving drug treatment (review at least twice a year).
The RM guidelines also included three levels of recommendations, RM-1, RM-2 and RM-3. There were based on the pre-selection of patients for assessment using a prior estimate of their risk of cardiovascular disease. The following steps were considered:
calculate a prior estimate of cardiovascular risk using age, gender, diabetes status, and default values for other risk factors;
prioritise patients by prior cardiovascular risk estimate;
assess cardiovascular risk factors in highest priority patients; and
treat assessed patients who meet the same criteria as in JBR strategies.
All treatment strategies required aspirin 150 mg as antiplatelet agent, and hydrochlorothiazide 25 mg and atenolol 50 mg for initial blood pressure lowering. In addition JBR-1, JBR-2, RM-1 and RM-2 required enalapril 20 mg for intensive blood pressure lowering, while JBR-1 and RM-1 required simvastatin 10 mg.
Economic study type
The study population comprised a cohort of individuals aged 30 to 74 years, reflecting the general population of the English general public in 1998. Patients with ischaemic vascular disease, those taking antihypertensive agents and those over 75 years of age were high priority groups, and thus were excluded.
The setting was primary care. The economic study was carried out in England, UK.
Dates to which data relate
The effectiveness data and some resource use data were derived from studies published between 1993 and 2001. The price year was not reported.
Source of effectiveness data
The effectiveness evidence was derived from a synthesis of completed studies and authors' assumptions.
A mathematical model was used to estimate the efficiency (total health service resources invested versus cardiovascular events prevented) of the six strategies for primary care-based prevention of cardiovascular disease in a hypothetical cohort of 2,000 individuals. The time horizon of the model was 5 years. The cardiovascular risk estimation was based on the Framingham CHD risk equation.
Outcomes assessed in the review
The outcomes estimated from the literature were:
the absolute reductions in 5 years for risk of stroke and risk of CHD; and
the impact on other major disease events with aspirin, thiazide and beta-blockers (usually hydrochlorothiazide and atenolol), angiotensin-converting enzyme (ACE) inhibitors (usually enalapril), and cholesterol-lowering treatment (usually simvastatin).
Distributions in the English population of systolic blood pressure and cholesterol concentration by age, gender, history of diabetes and smoking history in individuals who neither had prior cardiovascular disease, nor were receiving antihypertensive agents, were also estimated.
Study designs and other criteria for inclusion in the review
It appears that the primary studies have been identified selectively and a systematic review of the literature was not undertaken to identify them. Most of the evidence came from randomised clinical trials (RCTs), reviews of RCTs and meta-analyses, although no details on the primary studies were provided. The characteristics of the English population were derived from the 1998 health survey of England.
Sources searched to identify primary studies
Criteria used to ensure the validity of primary studies
Methods used to judge relevance and validity, and for extracting data
Number of primary studies included
Ten primary studies provided evidence.
Methods of combining primary studies
Investigation of differences between primary studies
Results of the review
The absolute reduction in stroke over 5 years was 20% with aspirin, 36% with thiazide and beta-blockers, 19% with ACE inhibitors and 29% with cholesterol-lowering treatment.
The absolute reduction in CHD over 5 years was 20% with aspirin, 17% with thiazide and beta-blockers, 20% with ACE inhibitors and 30% with cholesterol-lowering treatment.
The risk of other major adverse events over 5 years increased by 0.5% (based on an annual increase of major bleeding of 0.1%) with aspirin, whereas it did not change with the other treatments.
Methods used to derive estimates of effectiveness
The authors made two key assumptions that could influence the effectiveness results of the model.
Estimates of effectiveness and key assumptions
It was assumed that all eligible patients accepted and complied fully with treatment, and that no patient left or joined the practice over 5 years.
Measure of benefits used in the economic analysis
The summary benefit measure used was the number of cardiovascular events prevented. This was obtained from the mathematical model. Both stroke and heart disease events were considered. It was unclear whether the health benefits were discounted.
Discounting was relevant for some costs because of the 5-year time horizon of the model. An annual discount rate of 6% was applied when appropriate. The unit costs were not presented separately from the quantities of resources used for most cost items. The economic evaluation considered nurse time, blood tests and drugs (including dispensing costs). The cost/resource boundary of the health service was adopted. Resource use was estimated from published data and authors' assumptions. The costs came from the Personal Social Services Research Unit, standard costs of pathology services and average wholesale prices. The price year was not reported.
Statistical analysis of costs
The costs were treated deterministically.
The indirect costs were not considered.
Sensitivity analyses were performed to examine the robustness of the base-case results under several scenarios. In particular, prior prioritisation of the patients by estimated cardiovascular risk, prior knowledge of the patients' blood pressure, and the effects of not prescribing statins or ACE inhibitors.
Estimated benefits used in the economic analysis
The total benefits associated with each preventive strategy were only reported graphically.
The total costs associated with each preventive strategy were only reported graphically.
Synthesis of costs and benefits
The costs and benefits were combined by reporting the number of cardiovascular events prevented for any given allocation of resources. For any given allocation of resources to the primary prevention of cardiovascular disease, more cardiovascular events could be prevented under RM strategies than under the equivalent JBR strategies. A primary care team can prevent 13.5 events for 49,960 under strategy RM-2, or 13.5 events for 15,110 under RM-3. The most efficient strategy for a primary care team with this budget was therefore RM-3. A primary care team can prevent 16.7 events for 119,806 under strategy RM-1, or 13.5 events for 73,716 under RM-2. The most efficient strategy for a primary care team with this budget was therefore RM-2. For a primary care team with over 119,806 the most efficient strategy was RM-1.
For practices allocating one, two or three clinics a month to the primary prevention of cardiovascular disease, RM strategies dominated JBR strategies. In all cases, RM-1 was the most effective strategy. For one clinic, the incremental cost per cardiovascular event prevented was 10,518 for RM-2 over RM-3 and 17,808 for RM-1 over RM-2. For two clinics, the incremental cost per cardiovascular event prevented was 14,025 for RM-2 over RM-3 and 19,843 for RM-1 compared with RM-2.
The sensitivity analysis showed that RM strategies were more cost-effective than JBR options. In general, more cardiovascular disease could be prevented with the same health service resources by assessing only those patients pre-selected on the basis of a prior estimate of their risk of cardiovascular disease. Primary care teams with an electronic record of their patients' blood pressures could conceivably reduce the time for patient assessment to 5 minutes, thus favouring the JBR strategies. Statins and ACE inhibitors cost more than identifying and treating new patients, so strategies avoiding these may allow more disease to be prevented within available resources.
The pre-selection of patients for assessment was cost-effective in comparison with the assessment of all adults. Further, treatment of many patients with low-cost drugs was more efficient than prescribing a few patients intensive antihypertensive and statins. Thus, Rouse-Marshall (RM) strategies were more cost-effective than traditional guidelines.
CRD COMMENTARY - Selection of comparators
The authors justified the choice of the comparators, as novel strategies were compared with current guidelines for the prevention of cardiovascular disease in primary care. A detailed description of the new versus the old approach was provided, but the differences between the three new strategies and the three traditional approaches were not provided. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness
The effectiveness evidence came from several published sources, which included mainly clinical trials and meta-analyses. These represent robust sources of data, although no details on the primary studies were provided. The methods used to extract and combine the primary estimates were not reported. The authors made two important assumptions that could have impacted on the results.
Validity of estimate of measure of benefit
The summary benefit measure was specific to the study setting. It is not comparable with the benefits of other health care interventions.
Validity of estimate of costs
It appears that the costs included were consistent with the perspective adopted. However, a detailed breakdown of the items was not provided, and the unit costs were not presented separately from the quantities of resources used. This limits the possibility of replicating the analysis. The source of the costs was provided. Resource use was derived from both published data and authors' assumptions. The costs were treated deterministically. The price year was not reported, thus reducing the possibility of performing reflation exercises.
The authors did not compare their findings with those from other studies. They also did not address explicitly the issue of the generalisability of the study results to other settings. Few sensitivity analyses were carried out and, in general, the external validity of the analysis was low. The authors stated that conservative assumptions were made in the decision model, in order to bias the results of the analysis against RM strategies.
Implications of the study
The authors stressed that the benefits of following the JBR for the prevention of cardiovascular disease are modest and that the resource implications are substantial. Moreover, the efficiency of prevention of cardiovascular disease in primary care could be greatly enhanced by two innovations: prioritising patients for assessment on the basis of a prior estimate of their cardiovascular risk and avoiding costly drugs such as simvastatin and enalapril.
Marshall T, Rouse A. Resource implications and health benefits of primary prevention strategies for cardiovascular disease in people aged 30 to 74: mathematical modelling study. BMJ 2002; 325: 197-199
Other publications of related interest
Wolf PA, D'Agostino RB, Belanger AJ, et al. Probability of stroke: a risk profile from the Framingham study. Stroke 1991;22:312-8.
Gueyffier F, Boutitie F, Boissel JP, et al. Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men. A meta-analysis of individual patient data from randomized, controlled trials. Annals of Internal Medicine 1997;126:761-7.
Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of ACE inhibitors, calcium antagonists, and other blood pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Lancet 2000;356:1955-64.
LaRosa JC, He J, Vupputuri S, et al. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA 1999;282:2340-6.
Subject indexing assigned by NLM
Adult; Aged; Cardiovascular Diseases /economics /etiology /prevention & control; Computer Simulation; Cost-Benefit Analysis; England; Health Care Costs; Humans; Middle Aged; Models, Econometric; Patient Selection; Primary Health Care /economics; Primary Prevention /economics; Risk Assessment; Sensitivity and Specificity; Treatment Outcome; Workload
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