|Cost-effectiveness of rosuvastatin for primary prevention of cardiovascular events according to Framingham Risk Score in patients with elevated C-reactive protein
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.
This study assessed the cost-effectiveness of rosuvastatin for the primary prevention of cardiovascular events in patients with different Framingham Risk Scores (FRSs) and with elevated levels of high-sensitivity C-reactive protein and normal levels of low-density lipoprotein cholesterol. The author concluded that rosuvastatin was cost-effective, compared with conventional management, for patients with a FRS of over 10%. The methods appear to have been valid, which should ensure that the author’s conclusions are robust.
Type of economic evaluation
The objective was to assess the cost-effectiveness of rosuvastatin, for the primary prevention of cardiovascular events, for patients' with different Framingham Risk Scores (FRSs) and with elevated levels of high-sensitivity C-reactive protein (hs-CRP) and normal levels of low-density lipoprotein (LDL) cholesterol.
Rosuvastatin (20mg daily) was compared against standard management, which was defined as no statin therapy, with annual monitoring of lipid profiles and hs-CRP levels.
The analysis was based on a Markov model, with a 10-year time horizon. Two groups of patients were considered: those with a FRS greater than 10% and those with a FRS of 10% or less. The author stated that the analysis was carried out from the perspective of the health care system.
The clinical data were from the published Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study (Ridker, et al. 2008, see ‘Other Publications of Related Interest’ below for bibliographic details). This study compared rosuvastatin with no statin for patients with a median age of 66 years and a LDL cholesterol level below 130mg/dL and a hs-CRP level above 2.0mg/L. The key input for the model was the rate of cardiovascular events: non-fatal myocardial infarction, non-fatal ischaemic stroke, arterial revascularisation, hospitalisation for unstable angina, or death with a cardiovascular cause.
Monetary benefit and utility valuations:
The utility estimates were from published studies.
Measure of benefit:
Quality-adjusted life-years (QALYs) were the summary benefit measure and they were discounted at an annual rate of 3%.
The economic analysis included the costs of rosuvastatin, out-patient management, and the treatment of cardiovascular events. The drug costs were their average wholesale prices, out-patient management was from Current Procedural Terminology (CPT) codes, and the treatment of cardiovascular events was diagnosis-related group data from Medicare and Medicaid Services. The number of cardiovascular events was from the JUPITER study. All costs were in US dollars ($) and they were discounted at an annual rate of 3%.
Analysis of uncertainty:
One-way sensitivity analyses were carried out on all the inputs, except the probabilities of no event. High and low values were based on author’s assumptions and published sources. A probabilistic sensitivity analysis was carried out, with a sample of 10,000 and a sampling rate of once per Markov stage. In this analysis, all the inputs were assigned a predetermined distribution based on data from the JUPITER study.
In patients with a FRS above 10%, rosuvastatin led to a gain of 0.33 QALYs at a cost of $11,700, compared with usual care, resulting in an incremental cost per QALY gained of $35,455.
In patients with FRS of 10% or less, rosuvastatin led to a gain of 0.14 QALYs at a cost of $12,700, compared with usual care, resulting in an incremental cost per QALY gained of $90,714.
The most influential inputs, for patients with a FRS of over 10%, were the probability of a primary endpoint event, the cost of the statin, and the utility of a primary endpoint event. The most influential inputs, for patients with a FRS of 10% or less, were the cost of the statin, the probability and the utility of a primary endpoint event, the discount rate, and the utility of no event.
The maximum cost per QALY gained was $69,000 for patients with a FRS over 10%, and $165,000 for patients with a FRS of 10% or less.
The probability of being cost-effective at a threshold of $50,000 per QALY was 98% for patients with a FRS of over 10% and zero for those with a FRS of 10% or less.
The author concluded that prophylaxis with rosuvastatin was cost-effective, compared with conventional management, for patients with a FRS greater than 10%, elevated hs-CRP levels, and normal LDL cholesterol levels.
The comparators were appropriate as the intervention was compared against the usual approach for these patients. The two options were the comparators in the JUPITER study, which was the main source of evidence.
The clinical analysis relied on the results of the JUPITER study and its methods and results were published elsewhere. This publication should be consulted to assess these data inputs. In general, a randomised controlled trial should have high internal validity, but might not be generalisable to clinical practice. A limitation of the analysis was that it was assumed that the transitional probabilities, based on the JUPITER results only, were constant over time, while they might vary with a patient's age. QALYs were appropriately chosen as the benefit measure as cardiovascular events affect both expected survival and quality of life. Limited information on the derivation of the utility values was provided, which makes it impossible to judge their validity. The author undertook extensive sensitivity analyses on all the clinical inputs for the model.
The categories of costs and their sources reflected the viewpoint of the health care system. The costs of drugs and out-patient management were reported as unit costs, but cardiovascular events were reported as category totals and they were based on diagnosis-related group data that might not perfectly reflect the real cost of treatment. This is a typical approach when using Medicare tariffs. The author stated that the cost of rosuvastatin might change over time especially when its patent expires in 2016. Extensive sensitivity analysis on this parameter was undertaken. Discounting was reported; the price year was not clear, but appears to have been 2009.
Analysis and results:
The results were extensively presented, with both total and incremental findings. An appropriate incremental approach was used to synthesise the costs and benefits. Conventional discounting was applied. A justification for the selection of the time horizon was provided. The uncertainty was satisfactorily investigated, using valid approaches, and the findings were clearly presented and discussed. The Markov model was described and appears to have been appropriate for the disease. The author stated that the presence of diabetes mellitus was not considered, but might have favoured the statin group. The analysis appears to be specific to the US context and the transferability of the results was not explicitly addressed.
The methods appear to have been valid, which should ensure that the author’s conclusions are robust.
MacDonald GP. Cost-effectiveness of rosuvastatin for primary prevention of cardiovascular events according to Framingham Risk Score in patients with elevated C-reactive protein. Journal of the American Osteopathic Association 2010; 110(8): 427-436
Other publications of related interest
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, et al. Rosuvastatin to prevent cardiovascular events in men and women with elevated C-reactive protein. New England Journal of Medicine 2008; 359(21): 2195-2207.
Subject indexing assigned by NLM
C-Reactive Protein /drug effects; Cardiovascular Diseases /drug therapy /economics; Cost-Benefit Analysis; Diagnosis-Related Groups; Fluorobenzenes /economics /therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /economics /therapeutic use; Hypercholesterolemia /drug therapy /economics; Markov Chains; Models, Statistical; Primary Prevention /economics; Pyrimidines /economics /therapeutic use; Quality-Adjusted Life Years; Risk Assessment /methods; Rosuvastatin Calcium; South Dakota; Sulfonamides /economics /therapeutic use; United States; United States Food and Drug Administration
Date bibliographic record published
Date abstract record published