Jupiter Study- What does it really mean??

Dr. Steven Horvitz- Reading between the Lines:

Bringing you healthcare information you can trust!

The following is part of the abstract from the New England Journal of Medicine.

You will be hearing alot of information in the press about the benefits of cholesterol drugs, otherwise known as statins, especially Crestor, which was the drug used in this study.

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From the New England Journal Of Medicine:

n engl j med 359;21 www.nejm.org november 20, 2008

Rosuvastatin to Prevent Vascular Events in Men and Women
with Elevated C-Reactive Protein

Background
Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein
predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.

Methods
We randomly assigned 17,802 apparently healthy men and women with low-density
lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per
liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to
rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the
combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes.

Conclusions
In this trial of apparently healthy persons without hyperlipidemia but with elevated
high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.)

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ANALYSIS

The Jupiter (Justification for the Use of Statins in Prevention) study, another multimillion dollar study paid for by a pharmaceutical company, this time AstraZenaca.

AstraZeneca wants to justify that Crestor, a statin cholesterol lowering drug, be used in people with normal cholesterol as well as high cholesterol by the outcomes data in the Jupiter study.

Let's take a closer look.

The Jupiter study focused more on testing for inflammation in arteries, via high-sensitivity C-reactive protein as a criteria for inclusion. They want to prove that Crestor would lower inflammation in the arteries and thereby lower major cardiovascular events.

For each year of treatment out of 100 people, 0.17 in the Crestor group versus 0.37 in the placebo group had a heart attack, or an absolute difference of 0.2%. So it would take 500 people a year to take the drug to prevent one heart attack each year. Yet, up to 3% of people may get muscle or liver damage from the drug. That is 1 out of every 33 people.

So every year, 1 in 500 benefit, and 1 in 33 get side effects.

I would also like to follow the money trail and find out who is paying for the interpretations of the study. Below is the long list of consulting agreements to the pharmaceutical industry engaged in by the authors of the study and the funding by AstraZeneca below. This can also be found at the end of study. I have highlighted and underlined pertinent areas for emphasis.

Dr. Ridker reports receiving grant support from AstraZeneca, Novartis, Merck, Abbott, Roche, and Sanofi-Aventis; consulting fees or lecture fees or both from AstraZeneca, Novartis, Merck, Merck–Schering-Plough, Sanofi-Aventis, Isis, Dade Behring, and Vascular Biogenics; and is listed as a coinventor on patents held by Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease, including the use of high-sensitivity C-reactive protein in the evaluation of patients’ risk of cardiovascular disease. These patents have been licensed to Dade Behring and AstraZeneca.

Dr. Fonseca reports receiving research grants, lecture fees, and consulting fees from AstraZeneca, Pfizer, Schering-Plough, Sanofi-Aventis, and Merck;

Dr. Genest, lecture fees from AstraZeneca, Schering-Plough, Merck–Schering-Plough, Pfizer, Novartis, and Sanofi-Aventis and consulting fees from AstraZeneca, Merck, Merck Frosst, Schering- Plough, Pfizer, Novartis, Resverlogix, and Sanofi-Aventis.

Dr.Gotto reports receiving consulting fees from Dupont, Novartis, Aegerion, Arisaph, Kowa, Merck, Merck–Schering-Plough, Pfizer, Genentech, Martek, and Reliant; serving as an expert witness; and receiving publication royalties.

Dr. Kastelein reports receiving grant support from AstraZeneca, Pfizer, Roche, Novartis,
Merck, Merck–Schering-Plough, Isis, Genzyme, and Sanofi-Aventis; lecture fees from AstraZeneca, GlaxoSmithKline, Pfizer, Novartis, Merck–Schering-Plough, Roche, Isis, and Boehringer Ingelheim; and consulting fees from AstraZeneca, Abbott, Pfizer, Isis, Genzyme, Roche, Novartis, Merck, Merck–Schering-Plough, and Sanofi-Aventis.

Dr. Koenig reports receiving grant support from AstraZeneca, Roche, Anthera, Dade Behring and GlaxoSmithKline; lecture fees from AstraZeneca, Pfizer, Novartis, GlaxoSmithKline, DiaDexus, Roche, and Boehringer Ingelheim; and consulting fees from GlaxoSmithKline, Medlogix, Anthera, and Roche.

Dr. Libby reports receiving lecture fees from Pfizer and lecture or consulting fees from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Pfizer, Sanofi-Aventis, VIA
Pharmaceuticals, Interleukin Genetics, Kowa Research Institute, Novartis, and Merck–Schering-Plough.

Dr. Lorenzatti reports receiving grant support, lecture fees, and consulting fees from Astra-Zeneca, Takeda, and Novartis;

Dr. Nordestgaard, lecture fees from AstraZeneca, Sanofi-Aventis, Pfizer, Boehringer Ingelheim, and Merck and consulting fees from AstraZeneca and BG Medicine;

Dr. Shepherd, lecture fees from AstraZeneca, Pfizer, and Merck and consulting fees from AstraZeneca, Merck, Roche, GlaxoSmithKline, Pfizer, Nicox, and Oxford Biosciences; and

Dr. Glynn, grant support from AstraZeneca and Bristol-Myers Squibb.

So do you think there may be a potential conflict of interest relevant to the Jupiter study?

There is more to heart disease than cholesterol and inflammation. While they may be useful markers for potential disease, they do not necessarily become the main cause of disease. If they were, then you would expect much better outcomes.

An analogy I use is that cholesterol is like smoke, and heart disease is like the fire. Cholesterol, like smoke is a warning sign we can spot easily. Using Crestor and other statin drugs can lower cholesterol, or "blow away the smoke". But it does very little to put out the fire or reduce heart disease. When I see alot of smoke, I try to find natural lifestyle changes in diet and exercise to put out the fire. When that occurs the smoke goes away!!

Steven Horvitz, D.O.

Board Certified Family Medicine

Founder of The Institute for Medical Wellness

Top-Selling Prescription Drug Mismarketed to Women?

From the PharmaLive.com News Archive - Sep. 17, 2008

ITHACA, N.Y. – September 17, 2008 – Lipitor has been the top-selling drug in the world and has accounted for over $12 billion in annual sales. It has been prescribed to both men and women to lower cholesterol and reduce the risk of heart attack and stroke in patients with common risk factors for heart disease. However, a new study appearing in the Journal of Empirical Legal Studies was unable to find high quality clinical evidence documenting reduced heart attack risk for women in a primary prevention context. Furthermore, advertising omits label information relevant to women.

Theodore Eisenberg of Cornell Law School and Martin T. Wells of Cornell University assembled studies for a meta analysis of drugs’ effects on cardiovascular risk, taking into account all relevant studies reporting risks for both men and women.

Not one of the studies that included women with a mixture of risk factors for heart attacks provided statistically significant support for prescribing Lipitor or other statins to protect against cardiovascular problems. Pfizer’s claims of clinical proof that Lipitor reduces risk of heart attack in patients with multiple risk factors for heart disease does not appear to be scientifically supported for large segments of the female population.

In addition, Lipitor’s advertising repeatedly fails to report that clinical trials were statistically significant for men but not for women. Unqualified advertising claims of protection against heart attacks may therefore be misleading. Pfizer’s advertising also does not disclose critical portions of the Lipitor FDA-approved label, which acknowledges the absence of evidence with respect to women.

“Our findings indicate that each year, reasonably healthy women spend billions of dollars on drugs in the hope of preventing heart attacks but that scientific evidence supporting their hope does not exist,” the authors conclude.

This study is published in the September 2008 issue of the Journal of Empirical Legal Studies.

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This article shows the increased scrutiny of the pharmaceutical industries medical studies, medical claims and marketing practices.

As many of you already know, I am not a big fan of Lipitor or other statins, such as Crestor, Pravachol, Zocor, Mevacor and Lescol. Their use in prevention of heart disease leaves a lot to be desired. While not being a fan of statin drugs, I still am a fan of the pharmaceutical industry, just as I am a fan of the vitamin and neutraceutical industries, as long as their claims are valid and marketed truthfully.

I hope I am wrong, but this article from the Journal of Empirical Legal Studies may be a trial balloon for legal trouble for the pharmaceutical industry. We may soon see health insurers, Medicare and State Medicaid filing lawsuits worth billions of dollars to recover money spent on alleged false claims for Lipitor.

There are other methods of reducing heart disease risk, that do not rely on drugs. Eating and exercising properly. quitting tobacco, and reducing alcohol intake are just a few. The goal is not to lower your cholesterol number to the lowest it can go, but to increase your age to the highest it can go, but in a safe, effective and healthy manner that increases your quality of life. That is the goal of my practice, and I hope it is yours as well.

Steven Horvitz, D.O.

Board Certified Family Medicine

Founder of The Institute for Medical Wellness

The side effects of statins: Heart healthy and head harmful?

February 14, 2008 - This article from the heart.org is brought to you as a service from Dr Steven Horvitz and The Institute for Medical Wellness.

The side effects of statins: Heart healthy and head harmful?

February 12, 2008 Michael O'Riordan

New York, NY - The cognitive side effects, especially memory loss, associated with statins resurfaced again this week with an article in the February 12, 2008 issue of the Wall Street Journal, in which some doctors voiced concerns that the cholesterol-lowering medications, specifically atorvastatin (Lipitor, Pfizer), might be helping patients' hearts but actually putting their memory in jeopardy [1]. To date, evidence for this effect is only anecdotal.

In the article, Dr Orli Etingin, vice chair of medicine at New York Presbyterian Hospital, is quoted as saying that atorvastatin, the best-selling drug on the market, "makes women stupid." Etingin told the Journal that 24 of her female patients taking atorvastatin lost the ability to concentrate or recall words. While tests showed nothing irregular, the women regained full cognitive capacity when the statin was stopped, and some women did better on other statins.

The examples cited by Etingin, founder and director of the Iris Cantor Women's Health Center (New York), are anecdotal, but she said more studies are needed to assess the cognitive effects of statins, especially in women.

These concerns, despite their observational nature, are not new and have surfaced in medical journals and meetings, as well as the mainstream media, for a number of years. As the Journal notes, "Lowering cholesterol could slow the connections that facilitate thought and memory. Statins may also lead to the formation of abnormal proteins seen in the brains of Alzheimer's patients."

The evidence, however, linking statin use to declines in cognitive function or to the development of diseases such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, as well as to the possible protection from Alzheimer's and Parkinson's, are scattershot at best. In the Journal, reporter Melinda Beck notes that Pfizer, the maker of atorvastatin, states the drug has been tested in 400 clinical trials, with no evidence establishing a causal link between atorvastatin and memory loss. Cardiologist Dr Antonio Gotto (Weill-Cornell Medical School, NY) believes the benefits of the drugs outweigh the risks, telling Beck that he "would hate to see people frightened off taking statins because they think it's going to cause memory loss."

Dr Michael Miller (University of Maryland Medical School, Baltimore) commented to heartwire that he has heard anecdotal reports of cognitive declines with statin use but pointed to a recently published paper in Neurology, with lead investigator Dr Zoe Arvanitakis (Rush University Medical Center, Chicago, IL), showing that in nearly 1000 patients the use of statins was not related to incident Alzheimer disease, changes in cognition, or continuous measures of Alzheimer's pathology or infarction [2]. Numerous other articles, many covered by heartwire, show conflicting data supporting and not supporting a link between statin use and cognitive decline.

Speaking with heartwire, Arvanitakis said that her study involved both men and women and the results do not contradict the observational findings but simply do not support the anecdotal evidence seen in clinical practice.

"There is a lot of interest right now with respect to statins and cognitive decline and Alzheimer's, so we need to be aware of the anecdotal evidence," she said. "There are some people who do believe that statins have a negative effect on cognitive function, and others who believe it has a beneficial or protective effect, but right now we just don't know. . . . The bottom line is that the evidence is mixed."

Asked about the cognitive side effects, Dr Roger Blumenthal (Johns Hopkins University Medical Center, Baltimore) told heartwire he has had some patients "who think that they are not as sharp mentally on statins, but the numerator is very small and the denominator is very large." If there is a good reason to treat a patient with a statin, he'll try another drug or every-other-day dosing, but he noted that he does not need to do this frequently, as 90% or more patients "have no problems with statins."

Still, anecdotally, "the chronology can be very telling," Dr Gayatri Devi (New York University School of Medicine) told the Journal. She has treated six patients with memory loss traceable to statin use, with the changes occurring within six weeks of starting the cholesterol-lowering drug. "It's a handful of patients, but for them, it made a huge difference."

While cognitive declines occur in men, too, women are affected particularly harder because they are losing estrogen in menopause, something that can also cause changes in cognitive function, writes Beck. She quotes Women's Heart Program director Dr Nieca Goldberg (New York University School of Medicine) who prescribes statins only to women with elevated LDL cholesterol and who have already had an MI. For others, including those with high LDL cholesterol but no risk factors, Goldberg recommends dietary changes and exercise.

With the evidence all over the map and with observational reports not going away, studies are being conducted to examine the effects of statins on "thinking, mood, behavior, and quality of life," writes the Journal. The researchers, led by Dr Beatrice Golomb (University of California, San Diego), are collecting anecdotal experiences of patients on statins. Muscle aches are the most commonly reported side effect, thus far, with memory problems the second most common side effect, in approximately 5000 reports to date.

Sources

Beck M. Can a drug that helps hearts be harmful to the brain? Wall Street Journal, February 12, 2008. Available at: http://online.wsj.com/public/us.
Arvanitakis Z, Schneider JA, Wilson RS, et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology 2008; DOI:10.1212/01.wnl.0000288181.00826.63. Available at: http://www.neurology.org.


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Yet more information now being released about possible side effects of statin drugs which lower cholesterol. The experts mentioned above claim that there is only anecdotal evidence about statins and memory loss. I have seen memory loss in a small number of patients on these drugs. I have also seen other side effects, the most common being muscle aches and pains.

Statins are not the panacea to heart disease that the pharmaceutical industry has claimed. In the years to come I believe we will be using less of these medications as we find their effectiveness at preventing heart disease has been overstated.

Previous newsletters have discussed this topic.

February 6, 2008 : Cholesterol May Help Build Muscle

January 15, 2008 : Cholesterol Drug Zetia Doesn't Cut Heart Attack Risk: Study

I would also recommend www.spacedoc.net for more information on statin side effects.

Steven Horvitz, D.O.
Board Certified Family Medicine
Founder of The Institute for Medical Wellness