Heart Protection Study
Cost-effectiveness of simvastatin based on the Heart Protection Study: a randomised controlled trial of cholesterol lowering therapy with simvastatin
|Medical Research Council, British Heart Foundation and Merck
|Clinical Trial Service Unit, University of Oxford
|Borislava Mihaylova, Alastair Gray, Andrew Briggs,
The MRC/BHF Heart Protection Study (HPS) is a 'streamlined' randomised controlled trial to examine the effect (compared to placebo) of both cholesterol-lowering therapy and antioxidant vitamin supplementation on coronary heart disease (CHD) and non-CHD mortality.
The '2 x 2 factorial' design allows all patients to contribute to both assessments without affecting the trial cost or sample size requirements whilst also providing information concerning their combined effects. The 'streamlined' nature of the trial is such that only 'essential' data was collected. This minimises the workload for participating centres allowing more patients to be recruited including a wider range of high-risk patient. The rationale for this design is that a large trial including many types of patient is likely to be of much wider relevance than a smaller more homogeneous study. For further information about the Heart Protection Study and its results please visit http://www.ctsu.ox.ac.uk/~hps/.
As the clinical results for the antioxidant vitamin supplementation did not show any significant benefit during the trial the corresponding cost-effectiveness analysis became redundant. The economic analyses, therefore, focused on evaluating the cost-effectiveness of the statin intervention. Given the potential importance of expanding the scope of statin treatment in terms of health care budgets it is important to examine whether the value for money of treatment differs in different patient groups.
The within trial cost-effectiveness analysis published in the Lancet in 2005 reports the cost per major vascular event avoided and cost per vascular death avoided in patients at different baseline vascular disease risk. The lifetime cost-effectiveness of simvastatin was published in the BMJ in 2006 and reports the cost per life year gained and quality adjusted life year gained for people at different vascular disease risk and different ages at initiation of treatment. A paper presenting the extrapolation of the cost-effectiveness analyses to US context is submitted for publication.
Summary of major results of the cost-effectiveness analyses of the Heart Protection Study
- The five-year risk of first major vascular event among HPS participants in multivariate risk (with age, sex, prior disease at baseline, LDL-cholesterol, HDL-cholesterol, midpoint of systolic and diastolic blood pressure, and creatinine as predictive factors) quintiles ranged from 42% in the highest quintile to 12% in the lowest risk quintile.
- Allocation to simvastatin was associated with a highly significant 25% (20%–29%; p<0.0001) proportional reduction in the rate of first and subsequent major vascular events and a highly significant 22% (95% CI 16-27; p<0.0001) proportional reduction in UK hospitalisation costs for all vascular events, with similar proportional reductions in every subcategory of participant studied (including multivariate disease risk quintiles).
- Therefore, the baseline cardiovascular disease risk is an important determinant of the absolute effects of treatment on cardiovascular events and costs and its cost-effectiveness.
- A vascular disease decision model was developed based on the individual participant HPS data estimate lifetime risks of vascular events and costs of treatment and hospital admissions.
- At the April 2005 UK price of 4.87 pounds sterling (7 euros; 9 dollars) per 28 day pack of generic 40 mg simvastatin, lifetime treatment was cost saving in most age groups and vascular disease risk groups in the HPS.
- Gains in life expectancy and cost savings decreased with increasing age and with decreasing risk of vascular disease. People aged 40-49 with 5 year risks of major vascular events of 42% and 12% at start of treatment gained 2.49 and 1.67 life years, respectively.
- Treatment with statins remained cost saving or cost less than 2500 pounds sterling per life year gained in people as young as 35 years or as old as 85 with 5 year risks of a major vascular event as low as 5% at the start of treatment.
Implications: Our results suggest that treatment with statins is cost effective in a wider population than is routinely treated at present and it would seem appropriate to consider reducing the estimated level of vascular event risk at which statin therapy is recommended.
Mihaylova, B, Briggs, A, Hlatky, M, Armitage, J, Parish, S, Gray, A, and Collins, R (2009). Statin cost-effectiveness in the United States for people at different vascular risk levels. Circulation: Cardiovascular Quality and Outcomes, 2:65-72.
Mihaylova, B, Briggs, A, Armitage, J, Parish, S, Gray, A, and Collins, R (2006). Lifetime cost-effectiveness of simvastatin in a range of risk groups and age groups derived from a randomised trial of 20,536 people. BMJ 333(7579):1145-8.
Mihaylova, B, Briggs, A, Armitage, J, Parish, S, Gray, A, and Collins, R (2005). Cost-effectiveness of simvastatin in people at different levels of vascular disease risk: economic analysis of a randomised trial in 20,536 individuals. Lancet 365(9473):1779-85.