NHS Evidence Health Information Resources formerly National Library for Health

Statins provide continued protection against heart disease after patients stop taking them, reported two newspapers (11 October 2007). The newspapers accurately reported the results of long-term follow-up of a large randomised trial. The results appear reliable but may not be generalisable beyond the type of patient included in the trial.

Two newspapers (1,2) reported on 11 October 2007 that cholesterol-lowering drugs (statins) provide protection against heart attacks for up to 10 years after stopping treatment.
The reports were based on a report of long-term follow-up data from a large randomised controlled trial published in the New England Journal of Medicine (3). In the original trial, 6595 men with high levels of cholesterol but no history of heart attack were randomly assigned to treatment with a statin (pravastatin) or placebo for 5 years. Ten years after the end of the trial, when most participants had stopped taking pravastatin, the risk of death from heart disease or suffering a heart attack was 27% lower in the original pravastatin group compared with the placebo group. The risk of death from any cause was 12% lower in the pravastatin group.
The newspapers accurately reported the main findings of the study. The comment in The Times that the study raises the question of whether statins should be prescribed to younger people without evidence of heart disease was not derived from the research paper.

Evaluation of the evidence base for continued benefits of statin treatment

Where does the evidence come from?

The evidence comes from a long-term follow-up of the West of Scotland Coronary Prevention Study (WOSCOPS).

What were the authors' objectives?

To assess the long-term efficacy and safety of treatment with pravastatin.

What was the nature of the evidence?

This was a long-term follow-up of a randomised controlled trial involving 6595 men (average age 55 years) with high levels of low-density lipoprotein (LDL) cholesterol but no evidence of a previous heart attack. After the trial, patients were followed up using data from their medical records.

What interventions were examined in the research?

In the WOSCOPS trial, participants were randomly assigned to receive pravastatin (40 mg daily) or placebo. After the trial, patients were treated by their general practitioners in the community. Decisions on the use of statin therapy were made on an individual basis and were not based on specific guidelines or established practice.

What were the findings?

Five years after the end of the trial, 38.7% of patients in the pravastatin group and 35.2% in the placebo group were receiving statin therapy. At the time of long-term follow-up (approximately 10 years after the end of the trial), 18.7% of patients in the pravastatin group and 20.5% in the placebo group had died. The rate of death from coronary heart disease or suffering a non-fatal heart attack was 11.8% in the pravastatin group and 15.5% in the placebo group. Differences in both outcomes were statistically significant. The rate of death from cardiovascular causes was also significantly reduced in the pravastatin group. There were no significant differences between the groups in deaths from non-cardiovascular causes or in risk of developing or dying from cancer.

What were the authors' conclusions?

Five years of treatment with pravastatin was associated with a significant reduction in the risk of coronary events over the following 10 years in men with high cholesterol and no history of previous heart attack.

How reliable are the conclusions?

This was a long-term study with a large number of participants and a high rate of follow-up. Participants were followed in the groups to which they were originally randomised. The groups appear to have been similar at the start of the original trial and the methods used for data collection and analysis seem appropriate. The authors' conclusion that statin treatment has long-term benefits even after stopping treatment appears reliable for this group of patients, although the fact that some patients randomised to placebo later received statin therapy makes it more difficult to be sure of the magnitude of the effect. As noted by the authors, long-term studies of patients treated with statins following a heart attack or other coronary event have given contradictory results. Therefore, the results of this study may not be generalisable to other patient populations.

Systematic reviews

Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

There were no related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR), although there is one review which is currently being undertaken and will be available in the future (4). There were four related reviews on the Database of Abstracts of Reviews of Effects (DARE) (5-8).

References and resources

1. Cholesterol drugs 'protect you ten years after treatment stops'. Daily Telegraph, 11 October 2007, p8.

2. The pill of life. The Times, 11 October 2007, p1&4.

3. Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe SM. Long-term follow-up of the West of Scotland Coronary Prevention Study. New England Journal of Medicine 2007;357(15):1477-86.

4. Moore THM, Bartlett C, Burke MA, Davey Smith G, Ebrahim SBJ. Statins for preventing cardiovascular disease. (Protocol) Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004816. DOI: 10.1002/14651858.CD004816.pub2.

5. Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Archives of Internal Medicine. 2006;166(21):2307-13. [DARE Abstract]

6. Wilt TJ, Bloomfield HE, MacDonald R, Nelson D, Rutks I, Ho M, Larsen G, McCall A, Pineros S, Sales A. Effectiveness of statin therapy in adults with coronary heart disease. Archives of Internal Medicine. 2004;164(13):1427-36. [DARE Abstract]

7. Cheung BM, Lauder IJ, Lau CP, Kumana CR. Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes. British Journal of Clinical Pharmacology. 2004;57(5):640-51. [DARE Abstract]

8. Vrecer M, Turk S, Drinovec J, Mrhar A. Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke: meta-analysis of randomized trials. International Journal of Clinical Pharmacology and Therapeutics. 2003;41(12):567-77. [DARE Abstract]