Editor—With reference to the news item by Kmietowicz, in their press release the directors of the heart protection study did not mention that their results were substantially worse than in the previous Scandinavian simvastatin survival study (4S) (table).1,2,3
The way the results were presented exaggerates the benefit for the individual patient. The most interesting figure is survival because most myocardial infarctions heal with minimal cardiac dysfunction, if any. Tell a patient that his chance not to die in five years without statin treatment is 85.4% and that simvastatin treatment can increase this to 87.1 %. With these figures in hand I doubt that anyone should accept a treatment whose long term effects are unknown. For example, it was claimed that the study presented uniquely reliable evidence that simvastatin is not carcinogenic. But the study went on for about five years only, just like other statin trials. It is not possible to say anything about the risk of cancer because it takes decades to disclose chemical carcinogenesis in human beings. Heavy smoking, for example, does not induce lung cancer in five years. All the statins and also the fibrates have proved carcinogenic in rodents, and it scares me that, if the new American guidelines for cholesterol treatment are followed strictly, half of mankind may take statins in a few years and for the rest of their lives.4
Low cholesterol concentrations have been related to depression, cognitive impairment, and suppression of the immune system. Does a reduction of 1.7 % in mortality balance these risks? As in the previous trials, the effect of simvastatin was independent of the initial cholesterol concentration; patients with low concentrations benefited just as much (or just as little) as patients with high concentrations. The best results were seen in patients older than 75 years, an age group in which the lowest quartile of cholesterol concentration had the highest total and cardiovascular mortality.5
That statin treatment works in patient and age groups in whom a high cholesterol concentration is not a risk factor for cardiovascular disease shows that the benefit is not the result of cholesterol lowering. High or low cholesterol concentrations are markers for other, more important disease factors; they are not causal factors themselves.
Table.
Absolute risk reduction (%) in two trials of simvastatin
| Heart protection study1 | Scandinavian simvastatin survival study (4S)3 | |
|---|---|---|
| CHD mortality | 1.2 | 3.5 |
| Total mortality | 1.7 | 3.3 |
| All stroke | 1.5 | 3.5 |
| Any major CHD | 3.1 | 6.7 |
CHD=coronary heart disease.
References
- 1.Medical Research Council/British Heart Foundation Heart Protection Study. Press release. Life-saver: World's largest cholesterol-lowering trial reveals massive benefits for high-risk patients. Available at www.ctsu.ox.ac.uk/∼hps/pr.shtml (accessed 19 March 2002).
- 2.Kmietowicz Z. Statins are the new aspirin, Oxford researchers say. BMJ. 2001;323:1145. doi: 10.1136/bmj.323.7322.1145. . (17 November.) [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S) Lancet. 1994;344:1383–1389. [PubMed] [Google Scholar]
- 4.Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA. 1996;275:55–60. [PubMed] [Google Scholar]
- 5.Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. Cholesterol and all-cause mortality in elderly people from the Honolulu heart program: a cohort study. Lancet. 2001;358:351–355. doi: 10.1016/S0140-6736(01)05553-2. [DOI] [PubMed] [Google Scholar]