Wednesday, June 30, 2010

Crestor FAIL: JUPITER Busted

It is hard to enumerate all the problems with statins but the main one is that they fail to reduce coronary events and may actually be associated with higher mortality, cancer, congestive heart failure, lower serum testosterone, suicide, depression, brain damage, memory loss, pain syndromes, peripheral neuropathy, liver failure/jaundice and accidents.

We've talked about Crestor before: statins may make you dumb.

The problem is that Crestor is more potent therefore the side effects are more obvious now in clinical trials than they were before:
--'nonstatistically' increased %MI and revascularizations (see Nissen et al JAMA 2007, below)
--increased serum insulin
--increased serum glucoses
--increased incidence of new onset diabetes Type 2
--increased kidney failure and proteinuria
--increased percent of small dense atherogenic LDL particles (pattern B)

In a prior post, Nissen's JAMA 2007 article was discussed and a modified Table 6 showing event rates based on LDL (below average or above average, 87.5 mg/dl) presented. How statistical significance was not achieved is unbelievable to me but the results clearly make you wonder. With higher LDL (Greater than average LDL, last row), there was less myocardial infarctions (% MI) and less revascularization surgeries. Conversely, with the lowest LDL below average 87.5 mg/dl, the highest rates of myocardial infarctions (%MI) and revascularizations occurred.

Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, Wolski K, Crowe T, Desai MY, Hazen SL, Kapadia SR, Nissen SE. (Full PDF here) Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007 Feb 7;297(5):499-508. PMID: 17284700

Prior posts:
Atheroma Regression 101: Focus on HDL
Ancient Transporters LDL and HDL (The higher LDL the better)

Archives of Internal of Medicine recently published two articles on statin fails. The latest study re-examines the statistics in JUPITER, one of the seminal Crestor (rosuvastatin) trials that apparently showed regression on imaging however apparently has highly questionable outcomes in real life. PDF HERE. Crestor significantly raises basal insulin secretion. Insulin is a growth promoter -- need some (for muscles and fat storage) but not a lot. Insulin grows plaque, stiff arteries, obesity, waist-hip-ratios, skin tags, acanthosis nigricans, warts,inflammation, migraines, mood disorders, and benign and malignant tumours.

Prior post: Insulin -- Atherosclerosis, Hypertension, and CKD

Cholesterol Lowering, Cardiovascular Diseases, and the Rosuvastatin-JUPITER Controversy: A Critical Reappraisal
Michel de Lorgeril, MD et al. Arch Intern Med. 2010;170(12):1032-1036.

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.

Conclusion 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.


. said...

Related statin articles/information in the end of this portuguese article:
JUPITER outcomes and NNTs for men and women here:
Important recent statin related papers by Dr. Michel de Lorgeril:
La Nutrition interviews on Youtube with Dr. Lorgeril (how your french?):

. said...


Dr. B G said...



Hey I finally generated a blogroll... Harris gave me a hard time -- so it's finally up.

Love de Lorgeril -- he has got BALLS...


Neonomide said...

Of course Michel has balls - he already made AHA piss in their pants with his Lyon Diet-Heart trial. ^^