Atorvastatin: A Pharmacoeconomic Review of its Use in the Primary and Secondary Prevention of Cardiovascular Events
Greg L. Plosker
Katherine A. Lyseng-Williamson
Atorvastatin is a lipid-lowering agent that has been evaluated in a number of primary and secondary intervention studies. In the primary prevention trials ASCOT-LLA and CARDS, atorvastatin 10 mg/day significantly reduced cardiovascular events compared with placebo. A prospectively conducted economic analysis of the 3.3-year ASCOT-LLA trial showed that atorvastatin was associated with incremental cost-effectiveness ratios (ICERs) of _11_693 (UK) and _12_673 (Sweden) per event avoided (2002 values). Longer-term modelled analyses using data from CARDS showed ICERs of _8046 (Spain) and Lstg 6471 (UK) per QALY gained (2003/2004 values), and a US analysis showed atorvastatin was dominant versus no statin when modelled over the lifetime of a representative US diabetic primary prevention population. In a modelled analysis based on results of the IDEAL trial, which showed significant reductions in cardiovascular endpoints with high-dose atorvastatin (80 mg/day) compared with conventional-dose simvastatin in patients with stable coronary heart disease, ICER values were below the commonly used cost-effectiveness threshold of _50_000 per QALY gained in Norway, Sweden and Denmark, but were above this threshold in Finland (2005 values). A modelled US analysis that also included data from IDEAL and other sources showed an ICER of $US33_400 per QALY gained, assuming the incremental difference in acquisition cost between high-dose atorvastatin and conventional-dose simvastatin was $US1.40/day (2005 value). Most cost-effectiveness analyses with atorvastatin in patients with acute coronary syndrome used data from the 16-week MIRACL study, which showed a significant reduction in cardiovascular events with high-dose atorvastatin compared with placebo. Analyses were conducted in North America and Europe and showed that 31-86% of the acquisition cost of high-dose atorvastatin was offset by reductions in costs associated with cardiovascular events. Across five countries, ICER values ranged from ~=$US850 to $US4100 per event avoided (2000/2001 values). Another analysis conducted in the US used longer-term data and showed that high-dose atorvastatin versus conventional-dose statin was associated with an ICER of $US12_900 per QALY gained, assuming the daily difference in acquisition cost was $US1.40 (2005 value). In conclusion, atorvastatin has demonstrated beneficial effects on various cardiovascular endpoints in large, well designed primary and secondary intervention trials. These benefits in moderate- to high-risk patients were achieved at a relatively low incremental cost and, across the economic analyses, a substantial proportion of atorvastatin acquisition costs was offset by reductions in healthcare resource use associated with cardiovascular events. Cost-effectiveness analyses based on major clinical trials comparing atorvastatin with placebo, usual medical care, simvastatin or pravastatin have generally shown that atorvastatin is associated with favourable ICER values, often well below commonly used cost-effectiveness thresholds. These modelled analyses have the inherent limitation that projecting long-term outcomes beyond the time period of a clinical trial imparts a degree of uncertainty to the results. Nevertheless, while some findings were sensitive to changes in model assumptions, such as the long-term benefits of statin therapy, most sensitivity analyses showed that results of the base-case analyses were robust to plausible changes in key parameters. Although a clear pattern is not evident from available data, intuitively, the value of atorvastatin would be expected to increase with the patient's risk for serious cardiovascular events.
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