Amarin Corp Plc (AMRN)

[sts66]

The difference in the JUPITER trial is that JUPITER selected patients who did not have elevated LDL-Cs,..that's right, I said, they did not have elevated LDL-Cs, What they did have was elevated CRPs

Say what? How did the FDA approve it for lowering LDL-C then?!? How was the data presented to the FDA - you file for a drug lowering LDL-C but test it in a patient group with normal LDL-C, so I'd expect not much change in their levels, and they weren't "at risk" to start with - something stinks to high heaven here! Hey, I'm glad it got to market and likely saved many lives, but how it got approved is pretty bizarre from what you've said.

I have no doubt that lowering CRP was the real benefit for reducing CVE's, but CRP and other inflammatory markers were not well known to be keys to CVE risk way back when Crestor was approved - hell, they're STILL not accepted - insurance denies coverage for most of them as being "experimental".

Edit: Info from Wiki on Jupiter - appears the trial was held to sell Crestor despite negligible positive results, along with lots of negatives, along with profiting from the sale of the CRP test kits:

JUPITER was a randomized double-blind placebo-controlled study investigating the use of rosuvastatin in the primary prevention of cardiovascular disease. The trial focused on patients with normal low-density lipoprotein (LDL) cholesterol levels but increased levels of high-sensitivity C-reactive protein (hs-CRP). JUPITER was the first clinical trial to indicate that statin therapy may provide benefit to patients with low-to-normal LDL levels and no known cardiovascular disease.[1] The trial, which began in 2003, is directed by Paul Ridker of Brigham and Women’s Hospital.[2]

Because half of all vascular events occur in patients with normal or low levels of LDL cholesterol, JUPITER was designed to determine whether hs-CRP testing could identify these patients, and whether statin therapy could prevent cardiovascular events among them.[3] Elevated hs-CRP levels are thought to be a biomarker of inflammation, and have been associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death.[3]

Study details

The trial analyzed 17,802 patients without evidence of heart disease but with high CRP levels. In 2008, results presented at the American Heart Association meeting and published in the New England Journal of Medicine found that patients with low-to-normal LDL cholesterol receiving rosuvastatin had a lower rate of major cardiovascular events. Compared to patients taking a placebo, patients given rosuvastatin had reductions in LDL and CRP levels, and a reduction of 0.2% to 0.6% in their absolute risk of heart attack, stroke, and death at 1 year.[4][5][6] The study's authors estimated that the number needed to treat with rosuvastatin to prevent one cardiovascular event was 95 over 2 years, extrapolated to 25 over 5 years. The trial was stopped early by the study's independent data and safety monitoring board because the interim results met the study's predefined stopping criteria.[1]

The trial is sponsored by AstraZeneca, the marketer of Crestor (rosuvastatin).[2] The company saw an increase in its share of the U.S. statin drug market following the November 2008 New England Journal of Medicine publication.[7] The NEJM study's lead author, Paul Ridker, is the inventor of the CRP assay utilized in the study, and profits from its use.[8]

Adverse events

The researchers noted small but significant increases in the rate of physician-reported diabetes and glycated hemoglobin values in the rosuvastatin group, an effect that has also been seen in studies with other statins.[4] This finding, along with concerns over the safety of very low LDL levels, rosuvastatin's higher cost compared to generic statins, and the validity of biomarkers used in the diagnosis of cardiovascular disease, has been cited by those urging caution before expanding indications for statin treatment.[9][10][11][12]

A Specific Critique of the Jupiter study and Contrasting results from other studies

In 2010, a highly critical assessment of the Jupiter study was published in the Archives of Internal Medicine. The study, by de Lorgeril et al., had this to say in its Abstract and Conclusion: "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."