I was reading a commentary on the triumphant and much-trumpeted study purporting to show that Statins reduce mortality from Coronary Heart Disease by lowering LDL - if ever there was a pattern-book case of proving the need for skepticism!  In fact, I am reaching the point where I wonder if perhaps there is a special study course for those who write drug study results.

To quote Dr. Malcolm Kendrick  (of Red Flags Weekly)

"As this study presently stands, because they used different drugs, anyone can make the case that the benefits seen in the patients on atorvastatin had nothing to do with greater LDL lowering; they were purely due to direct drug effects of atorvastatin. And it is impossible for the authors to argue that this is not the case.

In addition, there is some very powerful evidence out there that directly contradicts the hypothesis that the degree of LDL lowering, and the protection against death are connected. This evidence comes from across the ocean, and is provided by another study which – perhaps to no-one's great surprise, attracted very little attention at all. "

And here it is, followed by another commentary by Dr. Kendrick:

Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia.

Matsuzaki M, Kita T, Mabuchi H, Matsuzawa Y, Nakaya N, Oikawa S, Saito Y, Sasaki J, Shimamoto K, Itakura H; J-LIT Study Group. Japan Lipid Intervention Trial.

Yamaguchi University Graduate School of Medicine, Ube, Japan. masunori@yamaguchi-u.ac.jp

Hyperlipidemia is a well-established risk factor for primary coronary heart disease (CHD). Although simvastatin is known to lower serum lipid concentrations, the protective effect of such lipid-lowering therapy against primary CHD has not been established in Japanese patients with hypercholesterolemia. The Japan Lipid Intervention Trial was a 6-year, nationwide cohort study of 47,294 patients treated with open-labeled simvastatin (5-10 mg/day) and monitored by physicians under standard clinical conditions. The aim of the study was to determine the relationship between the occurrence of CHD and the serum lipid concentrations during low-dose simvastatin treatment. Simvastatin reduced serum concentrations of total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C) and triglyceride (TG), by 18.4%, 26.8% and 16.1% on average, respectively, during the treatment period. The risk of coronary events was higher when the average TC concentration was or =240 mg/dl and the average LDL-C concentration was or =160 mg/dl. The incidence of coronary events increased in the patients with TG concentration or =300 mg/dl compared with patients with TG concentration <150 mg/dl. The high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of coronary events. The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin. A reasonable strategy to prevent coronary events in Japanese hypercholesterolemic patients without prior CHD under low-dose statin treatment might be regulating the serum lipid concentrations to at least <240 mg/dl for TC, <160 mg/dl for LDL-C, <300 mg/dl for TG, and 40 mg/dl for HDL-C.

PMID: 12499611  


"It showed that there is no correlation whatsoever between the amount of LDL lowering, and death rate. None. This, please remember, in a study that had ten times as many patients, lasted almost three times as long and – perhaps most importantly – used the same drug, at the same dose, in all patients. So it actually means something.

In contrast what did ....the other study ... really prove? It proved that atorvastatin protects against heart disease and death better than pravastatin. What it most certainly did not prove is that the more you lower the LDL level the greater the protection. "