Dr. Goldhaber should get a standing ovation from the statin industry!  It is incredible to consider the notion that statins should be used in primary prevention.  What Dr. Goldhaber fails to recognize is that by stopping the JUPITER trial early, there were exaggerated benefits attributed to the drug.  Haven't we learned enough about the dangers of long-term pharmacologic therapy?  Indeed, if the focus of the trial was the connection between rosuvastatin and lowered CRP, why not focus on the the more relevant issues surrounding why CRP was elevated in this supposed low-risk population?  If CRP is a reflection of systemic inflammation then there are numerous non-invasive approaches to CRP lowering in this regard.  How about a clinical nutritional approach that includes an anti-inflammatory diet augmented by appropriate consumption of Omega-3s?  The substitution of drugs for clinical nutritional approaches and lifestyle changes seems to be the paradigm for clinical practice by American physicians. 

As noted by others, the great problem with JUPITER is there was no true control group against which to compare the experimental groups (treated and untreated) who exhibited many characteristics of metabolic syndrome: over weight leading to glucose intolerance, hypertension, and environmentally induced combined hyper (dys) lipidemia. I pointed this out in a paper published in 2005 in Clin Chim Acta because one of the reviewers ask me to comment on the proposed JUPITER Study that had been peculiarly published in 2003 as a study to be performed - rationale and design - in Circulation, prior to any results being obtained.

Many studies have shown that after adjustment of confounding characteristics called metabolic syndrome, CRP adds little or nothing to risk assessment. Commonly, we statistically adjust for possible confounders. Since there was no true control group - persons living a healthier lifestyle - against which to adjust the results, one cannot assess the value of CRP. Even if the control group was not treated, it is likely that CRP would have been a weak or non-predictor of coronary disease after adjustment for the characteristic of metabolic syndrome against a group with few of these traits.

 It is now well known that fatness leads to systemic inflammation and an increase in acute inflammatory proteins, including CRP. As other have noted, it is this unhealthy lifestyle that needs to be addressed.  It is important to address these characteristic prior to an increase in inflammation and CRP. 

It may be appropriate to treat those persons with characteristics of metabolic syndrome who cannot slim down with a statin or niacin. Because of the many flaws in the JUPITER Study, it remains unclear if this is cost effective.

The argument of Dr. Levinson appears quite new and surprising to me. CRP may be considered a marker of risk just like e.g. high blood pressure. Has there ever been an argument that in an antihypertensive trial it is necessary to normalize for salt intake and body weight? Then it might be difficult to show that antihypertensives protect against stroke and other events for which high blood pressure is considered a marker of risk. To further play with the analogy: If, as argued above,  a "healthy" control group free of the risk factors associated with "essential" hypertension would be used as a "true" control group for antihypertensive trials, then antihypertensives would lose much of their protective power against cardiovascular events. Also with mild hypertension many physicians first try to modify lifestyle, often with modest success. 

However, I regret that this large trial was terminated early, because statins are used over very long periods and there is little really hard evidence on side effects with prolonged treatment. With broadening indications this becomes ever more important.

This is not exactly true. Blood pressure, as are various lipid conditions, is a true risk factor that causes the disease. Insulin resistance is also considered a true risk factor. CRP is a risk marker with little good evidence of being a causal factor. Most studies will show that blood pressure and cholesterols are independent markers, even after adjustment. This has been factually proven by studies showing their modification reduces disease. With the exception of age all of these markers show a weak but highly significant relationship with coronary disease. The relationship is significant because large numbers of persons are studied. The relationships are weak because the RR is in the vicinity of about 1.2 - 1.4, equivalent to a c-statistic of about 0.55. CRP is a risk marker  that adds slightly to improve the risk in some studies but not in others. The actual risk factor is  being overweight and insulin resistance and these are modifiable to provide greater protection from disease than reducing CRP with a statin while the weight remains the same.

The main problem with JUPITER is the definition of "normal" cholestrol levels. What Jupiter shows is that our conception of normal cholesterol is misguided. "Normal" LDL-C cholesterol is probably well under 100, not 130. Most coronary events occur in people with "normal" cholesterol. CRP is almost certainly an epiphenomenon and not causally related to coronary events. Jupiter may also be unmasking another of the pleiotropic effects of statins that we do not fully understand. JUPITER, as we learned from the early TIMI trials, is bound to be viewed with suspicion when the investigators have a financial stake in the outcome. I know and respect Dr. Ridker. However, given the current climate of suspiciion regarding the medical community and its ties to the pharmaceutical industry, which stands to gain or lose billions depending upon the outcome of studies such as JUPITER, we can not be too careful about avoiding even the appearance of a conflict of interest in the conduct of these studies. 

JUPITER deserves a standing ovation?  I think JUPITER deserves an investigation by the Department of Justice.