Statins might benefit healthy people
November 12th, 2008 | Published in Health | 2 Comments | View blog reactions
Or at least, this is what a study funded by AstraZeneca suggests. The study has been recently published in the New England Journal of Medicine — you can download a free pdf copy of it here (watch out, it opens in a new window).
In this blog post, I am going to examine and summarize the paper, and trying to draw some conclusions from it. Are the results reliable? Was the follow-up long enough, and their study sample of appropriate size? Find out just below the fold.
More than 17,000 patients of both sexes were randomly assigned to a group being treated with a daily dose of rosuvastatin, or placebo. The study found that, compared to the placebo group, patients being treated with the statin showed reduced cholesterol levels and C-reactive protein levels by a significant margin (50% and 37% respectively). These patients also showed reduced incidence of cardiovascular disease over a 2-year follow-up period. While rates of cancer and other causes of death were not affected, the study noticed an increase in “physician-reported diabetes”, which the results were unable to explain.
There are two main issues with this paper. The first is the strong involvement of the main authors with the funding agent — in this case a pharmaceutical company which is involved in the production and sale of the drug in question, rosuvastatin. The second one is the relatively short follow-up time: although all subjects were in age groups prone to cardiovascular disease — 60-year-old or more for men, 50-year-old or more for women — the study does not shed any light on possible long-term side-effects of statin use in healthy people. The increased diabetes reports might have turned into a substantial figure if a long-term study were conducted, but we are not going to know that until an independently funded study will try to shed light on this. Also, levels of C-reactive protein are not, at leats until now, widely recognized as a risk factor for cardiovascular disease.
Going back to the issue of the strong involvement of AstraZeneca in this study, the first thing I noticed about this paper, apart from the results of course, was the disclosure statement. Authors of academic and medical papers are required to disclose their affiliation with the funding agencies, as well as any personal benefit they might get from the results. This study was done for the JUPITER study group (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin); the head of the steering committee for the group, who is also the principal investigator, has tight professional relations with AstraZeneca. Moreover, he is
a coinventor on patents held by Brigham and Women’s Hospital that relate to the use of inflammatory bio-markers in cardiovascular disease, including the use of high-sensitivity C-reactive protein in the evaluation of patients’ risk of cardiovascular disease
C-reactive protein was used in this study as a possible indicator of risk of cardiovascular disease: in fact, the study concentrated on subjects that, by normal standards (LDL levels <130 mg/dL), are completely healthy, but who have more elevated levels of C-reactive protein, which has been showed to indicate a state of inflammation.
On the positive side, the study was conducted over a wide sample, representative of both genders and major racial groups. People with conditions that could make them prone to cardiovascular disease were excluded from the study, and so were those who were affected by diseases caused by, or resulting in, widespread inflammation. This was important, as the main hypothesis behind the study was that general inflammation levels, indicated by the abundance of C-reactive protein, could be a prognostic factor for the future occurrence of cardiovascular disease in otherwise completely healthy people. The paper is therefore also suggesting that levels of C-reactive proteins might be indicative of a susceptibility to cardiovascular disease in people with normal cholesterol levels.
In conclusion, although the results outlined in this paper will need further scrutiny, if confirmed, then they strongly suggest that healthy people could greatly benefit from a daily dose of rosuvastatin, in case it is shown that the statin is not directly responsible for an increase in diabetes cases in the test cohort.
Post Scriptum: Thank you to Alex Palazzo for including this post in the latest edition of the Molecular & Cell Biology Carnival.
P. M Ridker, E. Danielson, F. A.H. Fonseca, J. Genest, A. M. Gotto, J. J.P. Kastelein, W. Koenig, P. Libby, A. J. Lorenzatti, J. G. MacFadyen, B. G. Nordestgaard, J. Shepherd, J. T. Willerson, R. J. Glynn (2008). Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein New England Journal of Medicine DOI: 10.1056/NEJMoa0807646
December 4th, 2008at 3:10 pm(#)
Merrill goozner points out that: the median BMI (body mass index) was 28.3–thus at least 50% of participants were overweight and at least 1/3 would be categorized as obese. And also that “41 percent had metabolic syndrome, a suite of conditions that suggests the person is well down the road to developing Type II diabetes.”
http://www.gooznews.com/archives/001243.html
“The group on rosuvastatin developed diabetes at a higher rate than the group given a placebo, 3.0 percent versus 2.4 percent, an increase of six-tenths of a percentage point…
…While the overall rate of cardiovascular incidents fell from 2.8 percent to 1.6 percent by giving the statin, the number of so-called hard events — heart attacks and strokes, including those that were fatal — fell from 1.7 percent in the placebo group to 0.9 percent in the statin group, a drop of eight-tenths of a percentage point.
In other words, for every person who didn’t get a serious cardiovascular event, three-quarters of a person got diabetes.
…In this trial, 120 patients had to be treated for 1.9 years to prevent one serious cardiac event.”
Does that really impress you? 120 peopl;e must take crestor for 1.7 yrs for 1 person to avoid a cardiovascular event???
December 7th, 2008at 2:58 pm(#)
Heart attacks in the United States have been calculated to affect around 1 in 36 or 2.76%, or 7.5 million people in total. That means that you would expect around 3.3% of your 120 people to get a heart attack in the course of your study (numbers come with big caveats here). Of course, they say that people were apparently healthy, and according to that, their results would translate in a reduction in the frequency of attacks.
However, the BMI does raise concerns – and yes, we do not know whether these people were also given help in avoiding diabetes given that many of them were nearly obese.
To be honest, it’s the diabetes numbers that raise the most concerns for me, as this is not the first time they pop up in a study on statins. In addition to that, the amount of personal interests involved is another major issue – I think the study is valuable, but absolutely needs independent confirmation in a publicly funded study before anybody starts prescribing statins left and right.