Are Intensive Lipid-lowering Regimens an Optimal Economic Strategy in Patients with ACS? An Acute and Chronic Perspective

Roberta Ara; Rachid Rafia; Sue E Ward; Anthony S Wierzbicki; Tim M Reynolds; Angie Rees; Abdullah Pandor


Expert Rev Pharmacoeconomics Outcomes Res. 2009;9(5):423-433. 

In This Article


The literature review identified three relevant studies for inclusion in this review. The methodological approaches and the data used in the economic evaluations identified were well reported on the whole and the authors were contacted to clarify any areas of uncertainty. The findings from the studies agree that an intensive lipid-lowering strategy would be a cost-effective alternative compared with a standard-dose generic statin for individuals with ACS. These conclusions appear to be reasonably robust to the clinical data used to represent the effectiveness of the alternative treatments, the data used for the baseline risk and the transitions to subsequent events.

Two of the studies showed an intensive lipid-lowering strategy would be cost effective (compared with a standard dose) using data obtained from individuals receiving either simvastatin 80 mg/day or atorvastatin 80 mg/day.[3,105] Recently published data in individuals receiving simvastatin 80 mg/day shows an 11-fold increase in myopathy/myositis and defined premyositis giving a high risk of rhabdomyolysis.[4] Given this and the limited additional benefits associated with this dose, simvastatin 80 mg/day should not be considered as a treatment for intensive lipid lowering.

The models show substantial differences in the numbers of events predicted. This may be due to the differences in clinical practice in the different settings. The role of revascularization is dependent on underlying disease and in ACS there is an advantage to acute intervention provided that it occurs within 48 h of the clinical event.[30–33,106] Data from AtoZ shows differences in the intervention rates for different settings (2:1) despite the similar entry criteria used.[5] Consequently, while there are huge differences in the numbers of revascularization procedures predicted by Chan and Guideline,[3,105] the numbers may reflect country-specific clinical practice. The predicted number of revascularization procedures in Chan's model suggests that all ACS patients would receive a primary percutaneous transluminal coronary angioplasty in the USA. Conversely, the numbers predicted in the Guideline model suggest a more conservative approach is taken in the UK that reflects the greater use of medical therapies, particularly in the elderly where there is a greater likelihood of a conservative pharmacological-based management. In patients with angina, again, therapeutic choices differ. In the USA, percutaneous coronary intervention (PCI) is common for even minimal angiographic disease,[5,6,34–36] while Europe has long preferred aggressive medical therapy, with the recognition that in clinical trials PCI is a palliative intervention for symptomatic but not end point benefit.[36]

Several limitations were identified with the modeling approaches taken. First, the authors all took a conservative approach when extrapolating the clinical data beyond the duration of the clinical trials which is appropriate, particularly when using surrogate measures. However, there is some evidence that shows an additional benefit associated with long-term adherence to statins, which may not have been taken into account by using a conservative approach.[27,29] If the benefits are underestimated, the incremental cost–effectiveness ratios could be lower than calculated as one might expect the long-term incremental difference between an intensive and a standard treatment to be larger than currently modeled. Second, all the studies assumed that adverse event rates were minimal and these were not modeled explicitly. There is evidence that suggests adverse event rates are dose related although the evidence base is less robust for the higher doses. Adverse events may be more common in clinical practice as trial participants are usually younger, healthier and more closely monitored than patients in clinical practice. Many statin trials exclude over half of all screened patients, either owing to advanced age, renal failure, hepatic failure, hypothyroidism, or due to concomitant use of fibrates, macrolide antibiotics, antifungal agents, HIV protease inhibitors, verapamil or ciclosporin, which may increase the risk of adverse events.[37] Screening data from the recent Secondary Prevention of Acute Coronary Events – Reduction Of Cholesterol to Key European Targets (SPACE ROCKET) trial showed there were specific contraindications to simvastatin 40 mg/day in 55% of 5000 contemporary UK ACS cases.[106] Research exploring the adverse event rates for the higher dose regimens and the associations with adherence in general clinical practice would be informative for future evaluations.


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