Jumpin' Jupiter: When Should Statins Be Prescribed?

When the Jupiter study was released in November 2008, the results caused a hoopla. The study looked at AstraZeneca's Crestor cholesterol pill and measured levels of a protein called CRP that can indicate arteries are inflamed and point toward heart disease. But the results prompted debate over the extent to which CRP should be used as a guidepost for treating cholsterol and the wisdom in prescribing Crestor and other statins to people with low cholesterol ( background).

Now, a "critical reappraisal" has appeared in The Archives of Internal Medicine that calls the trial "flawed," because there were all sorts of methodological problems and that a "strong commercial interest" may have resulted in biased outcomes. Why? Nine of 14 Jupiter authors have financial ties to AstraZeneca and the principal investigator, Paul Ridker of Brigham and Women's Hospital, is a co-holder of the patent for the CRP test, which was known previously, and the head of the Data Safety Monitoring Board. And a second article also questions the veracity of the trial (see here).

In his defense, Ridker tells heartwire: "It has been written about publicly. But the data are the data. If we were trying to maximize the value of the patent, we would never have done this study, as we wouldn't have risked it not showing benefit. The patent is owned by my hospital, not by me, and they fully comply with extremely rigorous rules. Yes, I do get some financial benefit from it, but when talking about conflict you have to look at the data. And our data are good." Coming to his defense is Cleveland Clinic cardiologist Steve Nissen, who says "the paper is not science. It is more of an assault." As CardioBrief points out, two authors of the attack on Jupiter belong to the International Network of Cholesterol Skeptics, which loves to attack statins.

Separately, an analysis in the same journal finds no evidence that prescribing statins to patients at risk of heart disease reduces the chance of premature death in the short run. Data from 11 studies involving 65,229 people was evaluated - 32,623 patients on statins and 32,606 on a placebo. Over an average of 3.7 years of follow-up, 2,793 people died, including 1,346 on statins and 1,447 on placebo.

Taken together, the studies underscore a nagging argument in the medical community over the merits of prescribing statins for primary prevention of heart disease. The issue was only confounded further by a recent study that found statins may cause a higher risk of liver dysfunction, kidney failure, muscle weakness and cataracts.

"...in the short term, for true primary prevention, the benefit, if any, is very small," writes Lee Green of the Department of Family Medicine at the University of Michigan Medical School, in an editorial. "In the long term, although sincere advocates on both sides will try to convince us otherwise, we really must admit that we do not know. We need good research to find out and...research must be free of incentives to find any particular desired answer."

Meanwhile, an AstraZeneca spokeswoman writes to say that Jupiter was a rigorous and scientific study that looked at a previously unstudied patient population in which it was not clear as to whether a statin...could be of benefit. Patients in the study taking Crestor experienced a reduction in major CV events compared to those on placebo. This result had not been previously observed in a clinical trial for Crestor or any other statin.

The trial "was undertaken with a fully independent steering committee, data and safety monitoring board (IDMB), clinical endpoint committee, and academic study statistician. The protocol was designed and written by the study chairman and the trial data were analyzed by the academic study statistician and the academic programmer, all of whom take responsibility for the data. The IDMB conducted reviews to evaluate the progress of the trial, including periodic assessments of data quality and timeliness, participant risk versus benefit and other factors that could affect the study outcome, and made recommendations to the steering committee which, in turn, advised AstraZeneca."