Editor's Choice | This Week in BMJ | Press releases
BMJ No 7122 Volume 315 Letters Saturday 13 December 1997
Use of statinsSee Editorial by Muldoon p1554Results of different studies differed greatlyEditorWe do not agree with Freemantle et al that it is possible to be sure that the patients in 4S (Scandinavian simvastatin survival study) were at greater risk than those in the CARE (cholesterol and recurrent events) study.(1) All the participants in the CARE study had had a myocardial infarction.(2) In contrast, in 4S, a fifth of the patients had angina only(3) and were at a lower risk of major coronary events than the patients with myocardial infarction.(4) The maximum age was 75 in the CARE study and 70 in 4S; the incidence of myocardial infarction increases with age. There are important differences in the results of these trials. In 4S the benefit from simvastatin progressively increased up to serum triglyceride concentrations of 2.5 mmol/l (the upper limit for entry into 4S).(5) In contrast, in the CARE study there was no significant benefit at triglyceride concentrations above 1.6 mmol/l.(2) Benefit was observed throughout the range of decrease in cholesterol concentrations in 4S whereas in the CARE study there was no significant benefit below a low density lipoprotein concentration of 3.2 mmol/l.(2,3) The incidence of events in the placebo group in the CARE study may have been reduced by the lower low density lipoprotein cholesterol concentration on entry and a wider use of other effective drugs (for example, aspirin and angiotensin converting enzyme inhibitors). However, the benefit in the pravastatin group may also have been enhanced by these measures. If the results in the CARE study reflect a lower vascular risk why is the reduction in absolute risk marginally better in WOSCOPS (west of Scotland coronary prevention study), a trial in healthy subjects (see Freemantle et al's table(1) )? There are major differences in cost. The CARE study and WOSCOPS used pravastatin 40 mg/day. In 4S only 37% of patients were taking 40 mg simvastatin/day; the rest were taking 20 mg/day. In Britain the cost of both drugs is comparable at 20 mg and 40 mg doses. Furthermore, if the target concentrations were not achieved in the CARE study, cholestyramine was added to the pravastatin. It is not clear how many patients required cholestyramine. All statins may not be equal, especially in terms of cost needed to achieve clinically relevant end points. Consideration of cost benefit is further complicated by the reduction in admissions and procedures as a result of treatment(2,3); cost calculations are not readily undertaken. Whether guidelines should suggest 'first choice' statins remains a sensitive ethical issue. D P Mikhailidis
Reader, department of
chemical pathology and human metabolism
References 1 Freemantle N, Barbour R, Johnson R, Marchment M, Kennedy A. The use of statins: a case of misleading priorities? BMJ 1997;315:326-8. (4 October.) 2 Sacks F M, Pfeffer M A, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-9. 3 Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian simvastatin survival study. Lancet 1994;344:1383-9. 4 Pedersen T R, Kjekshus J, Olsson A G, Berg K, Faergeman O, Haghfelt T, et al. Scandinavian simvastatin survival study. Lancet 1994;344:1767-8. 5 Pedersen T R, Kjekshus J, Berg K, Faergeman O, Miettinen T, Olsson A G. Lipid changes and reductions in the incidence of major coronary heart disease events in the Scandinavian simvastatin survival study (4S). Atherosclerosis 1997;130(suppl):S7.
Home | Current issue | Past issues | Classified ads | Career Focus | Feedback Collections | About this site | About the BMJ | BMA | Medline
|