Authors' objectives:

To review the clinical and cost-effectiveness of the early administration (within 14 days of an ACS index event) of high-dose statins, aimed at reducing LDL-C to levels <70mg/dl (1.8mmol/l), in comparison with standard statin therapy aimed at reducing LDL-C to levels <100mg/dl (2.6mmol/l) in the treatment of patients at high cardiovascular risk following an ACS.

Authors' results and conclusions: Number and quality of studies and direction of evidenceThe effectiveness review included two RCTs: Colivicchi et al’s trial (n=81), and the PROVE IT-TIMI 22 trial (n=4,162). Both trials were well conducted adopting appropriate randomisation procedures and methods of analysis. Both compared high-dose atorvastatin (80mg/day) with standard lipid lowering therapy aimed at meeting an LDL-C target of <100mg/dl (2.6mmol/l). In summary evidence from both trials seemed to strongly support the effectiveness of early intensive lipid lowering with high-dose atorvastatin for high risk ACS patients. The main weight of evidence was provided by the larger PROVE IT-TIMI 22 trial (n=4,162). The median LDL-C levels achieved during follow-up in the PROVE IT-TIMI 22 trial were 62mg/dl (1.6mmol/l) in the high-dose (atorvastatin 80mg/day) group and 95mg/dl (2.5mmol/l) in the standard-dose (pravastatin 40mg/day) group. Kaplan-Meier event rates for the trial’s primary endpoint of death or a major cardiovascular event at two years were 22.4% in the atorvastatin group and 26.3% in the pravastatin group. This represented a 16% (95%CI: 5-26%, p=0.005) reduction in the hazard ratio for death or a major cardiovascular event in the atorvastatin group. A non-significant trend favouring high-dose atorvastatin emerged at 30 days and was consistent over the course of the trial. Intensive lipid lowering with atorvastatin also had a consistently beneficial effect on the trial’s secondary endpoints. At two years there were statistically significant reductions in the risk of recurrent unstable angina (29%, p=0.02) and the need for revascularisation (14%, p=0.04), and non-significant reductions in the rates of death from any cause (28%, p=0.07) and death or myocardial infarction (18%, p=0.06). Stroke rates between the groups did not differ significantly.

Authors' recommendations: For ACS patients the early use of high-dose/potency statins significantly reduces the risk of death or a major cardiovascular event in comparison with standard lipid lowering regimens. Overall, modelling of the cost-effectiveness of high-dose relative to standard-dose statins appears to support the use of high-dose statins for ACS patients. If we accept that the model’s results, derived from the US health-care system, are generalisable to the UK, intensive lipid lowering with high-dose statins seems highly likely to be cost-effective at drug price differentials and willingness to pay thresholds likely to be operating in the NHS.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.birmingham.ac.uk/Documents/college-mds/haps/projects/WMHTAC/REPreports/2008/High_Dose_Statins.pdf

Year Published: 2008

URL for published report: http://www.birmingham.ac.uk/research/activity/mds/projects/HaPS/PHEB/WMHTAC/REP/reports-list.aspx

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England

Organisation Name: West Midlands Health Technology Assessment Collaboration

Contact Address: Elaena Donald-Lopez, West Midlands Health Technology Assessment Collaboration, Department of Public Health and Epidemiology, University of Birmingham, Edgbaston, Birmingham B15 2TT Tel: +44 121 414 7450; Fax: +44 121 414 7878

Contact Name: louise.a.taylor@bham.ac.uk

Contact Email: louise.a.taylor@bham.ac.uk

Copyright: West Midlands Health Technology Assessment Collaboration (WMHTAC)