Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal.
BACKGROUND
Among the recently reported cholesterol-lowering drug trials, the JUPITER (Justification for the Use of Statins in Primary Prevention) trial is unique: it reports a substantial decrease in the risk of cardiovascular diseases among patients without coronary heart disease and with normal or low cholesterol levels.


METHODS
Careful review of both results and methods used in the trial and comparison with expected data.


RESULTS
The trial was flawed. It was discontinued (according to prespecified rules) after fewer than 2 years of follow-up, with no differences between the 2 groups on the most objective criteria. Clinical data showed a major discrepancy between significant reduction of nonfatal stroke and myocardial infarction but no effect on mortality from stroke and myocardial infarction. Cardiovascular mortality was surprisingly low compared with total mortality-between 5% and 18%-whereas the expected rate would have been close to 40%. Finally, there was a very low case-fatality rate of myocardial infarction, far from the expected number of close to 50%. The possibility that bias entered the trial is particularly concerning because of the strong commercial interest in the study.


CONCLUSIONS
The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.
de Lorgeril
Michel
M
Laboratoire Coeur and Nutrition, Faculty of Medicine, Université Joseph Fourier and Centre National de Recherche Scientifique, Grenoble, France. michel.delorgeril@ujf-grenoble.fr
Salen
Patricia
P
Abramson
John
J
Dodin
Sylvie
S
Hamazaki
Tomohito
T
Kostucki
Willy
W
Okuyama
Harumi
H
Pavy
Bruno
B
Rabaeus
Mikael
M
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood*; D004359:Drug Therapy, Combination; D005464:Fluorobenzenes / Q000627:therapeutic use*; D005602:France / Q000453:epidemiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D011743:Pyrimidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002784:Cholesterol