| The NOT so "fantastic" side of CRESTOR despite sudden UK media push on behalf of AstraZNovember 10 2008 at 12:42 PM | admin |
| Article by Duane Graveline MD MPH, former USAF Flight Surgeon, former NASA Astronaut, retired Family Doctor:
http://www.spacedoc.net/crestor.htm>
Crestor® Side Effects ( Rosuvastatin )
The release of Crestor, the newest of the statin drugs was associated almost immediately with a need for a revised package insert because of a rash of adverse drug reports of muscle and renal toxicity. What else could you expect from Astra-Zeneca's rosuvastatin, promoted as the most powerful of the powerful statin drugs already on the market?
Suddenly, increased numbers of rhabdomyolysis reports began to surface in Crestor users associated with secondary kidney damage and a more ominous threat of specific primary renal toxicity as well and the necessity to issue emergency warnings advising doctors to exercise special caution in the use of this drug with hypothyroidism, renal insufficiency, Asian sub-population groups and cyclosporine and gemfibrozil takers. Not a terribly auspicious welcome for Crestor, this new statin drug known for strength in a market already dominated by other powerful statins.
In any society of thinking people, the question of necessity comes to mind immediately and Astra-Zeneca's explanations are, too me, far from satisfactory. A possible positive feature about Crestor was rooted in my personal experience with cognitive dysfunction from statin drug use.
Because Crestor was deemed more hydrophilic (water loving) rather than the lipophilic (fat loving) character of its statin competitors, I expected Crestor's use to be much less frequently associated with cognitive dysfunction but, like its sister hydrophilic drug, Pravachol, any benefit from hydrophilicity is incomplete and therefore unreliable and precious little gain from Crestor is easily offset by its greater tendency for severe side effects of a non-cognitive nature due to its very strength.
Receive the free spacedoc e-mail newsletter!
Crestor is just another strong statin, using the same mechanisms as the others and having all the inherent potential for side effects. My books tell of the inevitable harm to the mevalonate tree by statins but that was the only way drug company biochemists could inhibit cholesterol so they did it anyhow, regardless of the potential for collateral damage. Does this action reflect sound judgment? They knew that inhibiting cholesterol at this point would also inhibit CoQ10, dolichols, normal phosphorylation and selenoprotein. Every doctor once knew this for they were taught it in medical school but few have bothered to review what mevalonate inhibition really means. In my books I refer to this as "girding" of the mevalonate tree.
We have now learned much more about the side effects of Crestor. We have learned that cognitive, muscle and nerve problems, due to the inevitable impairment of glial cell cholesterol synthesis and mevalonate blockade are only part of the problem. The Crestor side effect potential, that it shares with all other statins, is far more basic than this. Now we have learned that mitochondria are an inevitable target of statins. Because of inhibition of CoQ10 availability with its powerful anti-oxidant effect, mitochondria are left fully exposed to the mutagenic effect of free radicals. The resulting mutations of mitochondria are what is causing the legions of permanent, disabling side effects.
Permanent neuropathy, permanent myopathy, chronic neuromuscular degeneration, and Parkinsonism and ALS-like cases now are thought by some to be the result of permanent statin-induced, mitochondrial damage. Furthermore, the inherent ability of the body to identify and correct the daily load of mutations is impaired because of the previously unrecognized effect of dolichol inhibition from the earlier mevalonate blockade. If this is beginning to sound like a domino effect, you are right. We still are seeing the dominos topple one by one as time goes by - the result of marketing a class of drugs before it was fully investigated.
Dolichols are vital to the synthesis of glycoproteins, which in addition to thousands of other duties must serve in this identification and correction of DNA damage role. Glycohydrolases, a member of the glycoprotein family of molecules is vital to this function. Five years ago we hardly knew what dolichols were and now we find them involved in so many unexpected places. So I must bring to your attention that Crestor shares all this with the other statins. Its potential for damage goes far beyond the original suspicions.
Here are just some of the reports I have received from readers of my books and from websites regarding their personal experiences of Crestor Side Effects.
1.) I have taken statin drugs for years. Not many they have not tried me on, the latest being Crestor 10 mg, Tricor 165 mg and Zetia 10 mg all at the same time. Almost immediately upon taking these drugs, I started experiencing pain in my Achilles tendon and at times can hardly walk now. I have seen an Orthopedic Surgeon who tells me my Achilles tendon is deteriorating. I cannot help but feel this has come from 15 years of taking Statin drugs. I am not an athlete. I had been walking on a treadmill 2 miles about 3 times a week. But no other stress to my feet that should have caused this.
2.) In April 2004 my husband began taking Crestor. In October, he suffered an episode of angina, called 911 and spent 2 days in the hospital. A week later, he was hospitalized again with similar symptoms and in the hospital 3 days. A heart cath revealed a little blockage in one artery (I think 20-30%), but no explanation for the symptoms. We believe it was the Crestor. The cardiologist switched him to Pravachol, which gave him achy joints. He stopped taking the Pravachol, and now is not taking anything for his cholesterol. I am worried, because he has a history of very high cholesterol (over 300), he smokes, and he drinks too much and gets very little exercise. We have found it difficult to stick to a low-fat diet, although we are eating better overall. His doctor has suggested niacin and has given us samples of Zetia and Niaspan, but he hasn't tried these yet.
3.) I feel terrible and do not look a very pretty sight either. But doctors are not associating my pains with my current use of Crestor. I have undergone various tests, which failed to show a cause for my pains, except that I have an enlarged uterus and ovarian cysts that according to doctors wouldn't normally cause the pains that I describe. I am particularly worried now about your mention of memory loss, as this is another problem that I noticed to be developing and some of my family and friends have also noticed. However, I tend to associate with the fact that I am unable to have a full good night sleep due to my pains. It would be really interesting to hear if other people are (or have in the past) experiencing similar pains.
4.) My cholesterol has been elevated for years and I was always afraid to go on the statin drugs with various side affects. I was on Zetia for awhile and during my last physical my triglycerides were high and my cholesterol was 255. My doctor decided I needed to go a statin. He said that he had good results with Crestor. I am a nurse and I questioned him about its recent publicity about it safety. He said he did not hear anything bad about it. I took it for a little over a week and I first started to feel heaviness in both legs. The next day I had pain in both arms. I work as a vascular access nurse and my both of my hands felt tight and stiff like I suddenly had arthritis. I had trouble holding my IV needle. At night I had significant pain in both legs and arms. I had to take pain medicine. I also felt very fatigued-like I could not go on. I saw my doctor at the hospital where I work and said I feel terrible. I had already stopped the Crestor. He ordered a cpk blood test and I haven't heard the results yet. It has been 2 days since I have stopped the Crestor and my pain has subsided and my energy level is normal and I feel much better.
5.) I recently began taking Crestor on advice from my doctor because my cholesterol is on the high side of normal and there is a small build-up in the neck arteries. Since starting this drug I have experienced pain in the right side which is very severe at times. I went to the ER and they ran tests - checking out shingles, appendicitis and kidney stones - and everything is "normal". I am still having the pain but see no positive reason to have it checked out again. I am also experiencing a "don't care" attitude. I am crying over nothing and have no ambition to do anything. This is not like me at all. I have not done a lot of investigation but what I have seen has led me to stop taking the drug until I can see the doctor.
6.) Dr. prescribed Crestor about 8 weeks ago due to cholesterol of 270+-. I have always been stiff jointed and inflexible, but it does seem that I am hurting more now than ever, particularly my feet. I am male, 42, 170 pounds, reasonably fit, don't smoke, and except for the cholesterol am in good shape. I have also noticed decreased energy levels. Not sure I can definitively tie the aches and tiredness to more than turning 42, raising small kids, and running a business, but your web site does make me wonder if I would do well get off of it. I have not experienced any memory problems I am aware of, but being a pilot that is also a concern. Thanks for the information on your site.
7.) I've tried several of the statin drugs and at the present time take Crestor. I told my doctor they cause me problem. When I was on Lipitor I was miserable, Muscle aches, and couldn't sleep well, bowel problem and memory problems and a real short fuse (temper).
She persuaded me to try Crestor. I only thought I was miserable with Lipitor, Crestor is worse. I'm having problem sleeping again, muscle aches but most of all my temper and the aggressiveness you talk about.
I've got some blockage in my arteries, worse one is around 50%, and I'm 61 with no heart problems in my family. My overall cholesterol is 293 without drugs and my good cholesterol is 71. I think I would rather take my chances with a heart attack than take statin drugs.
8.) Sudden weight gain, no energy, and such sore muscles I must really concentrate to get out of bed in the morning to go to work. On weekends, I sleep around the clock if I do not set my alarm clock which I have never had to do before. In general, I'm losing an interest in life...just going through the motions. Have only been on this drug for 4 weeks since my GP decided my cholesterol was too high...over 300. Since both parents died of heart attacks, I suppose he is being careful but my eating habits have always been careful except now, at my age, fresh fruits & vegetables are very hard on my digestive tract.
9.) I am a little concerned about Lipitor (which I took a while back), and Crestor that I am on now. The doctor I am going to took me off Lipitor and put me on Crestor because of muscle weakness in my legs which started shortly after I started Lipitor. She said there were no long term effects with Lipitor, but I still have the problem. She tried to blame it on age, but I'm only 54 and never had the problem before.
10.) I am a 66 year old woman with a history of heart disease. In spite of a past history of liver problems and also on Ketoconazole, my new Cardiologist put me on Crestor in Sept. 03. He also gave me Zetia. I then experienced severe muscle system failure related to the intestine, followed by weakness in the legs, arms, and other places. I took Crestor for one year in which I suffered violent pain in the abdomen, nausea, and general weakness overall. I could not stand up. I fell several times and injured myself. I could not drive, nor stand long enough to cook. When I finally received a diagnosis, I learned that I had raging hepatitis. I instantly discontinued the two medications, and began to recover from the hepatitis. I have since discovered that this drug also causes Rhabdomylosis. I have researched this condition and I believe that I did have it. When I brought it up to my primary Dr. She said that I did not have it. I agree with her, but I still believe I did have it for a year. By the time I found out about the Rhabdo, I had been off the medication for three months. My urine looked like old tea. I took a questionnaire and answered positive to every symptom.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
Crestor and Rhabdomyolysis
|
| | Author | Reply | What UK media are NOT telling you
| Crestor needed revised label warning due to muscle and renal toxicity | November 10 2008, 12:45 PM |
"The release of Crestor, the newest of the statin drugs was associated almost immediately with a need for a revised package insert because of a rash of adverse drug reports of muscle and renal toxicity. What else could you expect from Astra-Zeneca's rosuvastatin, promoted as the most powerful of the powerful statin drugs already on the market?
Suddenly, increased numbers of rhabdomyolysis reports began to surface in Crestor users associated with secondary kidney damage and a more ominous threat of specific primary renal toxicity as well and the necessity to issue emergency warnings advising doctors to exercise special caution in the use of this drug with hypothyroidism, renal insufficiency, Asian sub-population groups and cyclosporine and gemfibrozil takers. Not a terribly auspicious welcome for Crestor, this new statin drug known for strength in a market already dominated by other powerful statins..."
|
| 'MORE dangerous than any other statin' ?
| "WARNING ABOUT CRESTOR" and the call to pull it from US shelves | November 10 2008, 12:52 PM |
http://www.onlinelawyersource.com/crestor/warning.html>
Warning About Crestor
New Crestor warnings have recently been issued by European and Canadian regulators, attempting to strengthen labeling requirements on the cholesterol-lowering product that has been linked to rare and potentially life-threatening side effects at high dosages. A warning label, released by Crestor manufacturer Astra-Zeneca Pharmaceuticals, tells doctors in all 22 EU countries to start their patients on the low 10-milligram dose of Crestor instead of higher dosages for a four-week trial period. Crestor labels in the United States already carry this warning, the FDA claims. Health Canada has also recently issued a warning to its citizens, explaining the high risk for life-threatening side effects, while the scientific journal The Lancet decided to publish a letter from Dr. Sidney Wolfe of Public Citizen, demanding that Crestor be pulled from shelves immediately.
Crestor is a prescription drug used to lower patients'' cholesterol when natural measures have been unsuccessful. While it has been effective on its own, Crestor should be used in addition to a healthy diet and regular physical activity. Crestor lowers cholesterol by reducing the amount of fatty LDL''s, or so-called "bad cholesterol," in the blood. It also raises the amount of HDL''s, or "good cholesterol," creating an overall reduction in the body''s cholesterol level. Crestor falls into the statin category, a popular and prevalent class of cholesterol-fighting pharmaceuticals. Statins work to reduce the risk of heart disease and stroke in patients with abnormally high cholesterol levels. But along with their health benefits, all statins have a dangerous potential side effect. They put the patient at risk for injury to the body''s muscle tissue, and can cause a muscle-destroying disease called rhabdomyolysis. When rhabdomyolysis dissolves muscle tissue it releases substances that are harmful to the kidney and potentially life-threatening.
The extent of the physical side effects from Crestor was unknown at the time the FDA approved the drug for distribution in the United States. Although Public Citizen, a consumer watchdog group, protested the approval of Crestor and had it delayed by nearly a year, the FDA found no adverse effects on the muscles during the clinical trials of the product at appropriate doses. But within the first year after Crestor was available for prescription, a 39-year old American woman died from kidney damage as a result of rhabdomyolysis. In addition, a handful of patients throughout the U.S., U.K. and Canada had suffered serious side effects while taking Crestor at normal doses, including kidney damage and kidney failure.
This prompted Public Citizen to petition the FDA for a ban on Crestor, alleging that its side effects are more dangerous than any other statin because of the muscle damage produced in the absence of rhabdomyolysis. Crestor manufacturer Astra-Zeneca maintains that their product is no different than any other statin on the market today, with over two million Crestor prescriptions written to date. Despite this claim, the FDA continues to warn physicians to recommend appropriate dosages for their patients and inform them of the potential risk of muscle injury that can be caused by Crestor. Patients taking Crestor or any other statin, the FDA says, should call their doctor immediately if they exhibit symptoms such as vomiting, nausea, dark urine, fever, or muscle pain.
Defective Drugs Breaking News
"FDA rejects petition to ban Crestor"
The consumer advocacy group Public Citizen submitted a petition to the FDA a year ago asking the agency to immediately withdraw the anti-cholesterol drug Crestor, but the agency has denied its request.
Crestor belongs to a group of drugs ...
» Read More
"Asians taking Crestor may be at higher risk for rhabdomyolysis"
The FDA has announced that Crestor is being relabeled to add a warning that starter doses should be reduced in Asian-American patients, as well as some other higher risk patients.
A clinical trial found that levels in Asian patients were d...
» Read More
"Public Citizen calls FDA Crestor announcement an act of cowardice"
The FDA announced a revised drug labeling for the cholesterol-lowering drug Crestor would be added, warning of the serious muscle damage called rhabdomyolysis.
A clinical trial found levels of Crestor in Asian patients were double those of C...
» Read More
Other Areas of Drug Recall
|
| admin
| In June 2004, the BBC covered the call for a ban on Crestor | November 10 2008, 12:57 PM |
>
Last Updated: Friday, 25 June, 2004, 13:13 GMT 14:13 UK  
|
Call to ban anti-cholesterol drug
|
 Doctors want statin side effects to be closely monitored | One of the newest cholesterol-lowering drugs should be removed from the market because of safety concerns, an expert has said.
Dr Sidney Wolfe from US consumer group Public Citizen says the statin Crestor (rosuvastatin) carries a higher risk of side effects than other statins.
Writing in the Lancet, he says the risk of muscle wastage and kidney failure means the other statins should be used.
Manufacturer AstraZeneca says Crestor is as safe as other statins.
Statin medicines have been available in the UK for the last 14 years.
There are five different types available, including rosuvastatin, licensed for use in the UK by the government's Medicines and Healthcare products Regulatory Agency.
|
 [There] are compelling reasons to remove rosuvastatin from the market before additional patients are injured or killed 
Dr Sidney Wolfe from Public Citizen |
All statins work to lower cholesterol which, in turn, reduces the risk of cardiovascular disease - the biggest cause of death in the UK.
Rosuvastatin was launched last year in the UK and about 110,000 patients had received the drug by March 2004.
In May this year, rosuvastatin's manufacturer AstraZeneca sent a letter to doctors reminding them to reserve the highest doses for patients at highest risk of heart disease because of safety concerns.
Safety concerns
The concern was about the drug's link with a condition called rhabdomyolysis - a muscle wasting condition that can lead to kidney damage and failure.
Other statins also carry a risk of rhabdomyolysis and kidney failure, which is dose related.
The government's Committee on Safety of Medicines monitors these side effects.
It says about one case report of rhabdomyolysis has been received for every 100,000 patients, for each year of treatment with any statin.
A detailed analysis by the CSM and MHRA of the safety information for rosuvastatin at the end of its first year suggested that although the top (40mg) dose benefits a small percentage of patients, it may be associated with a higher rate of side effects, including rhabdomyolysis.
The CSM received six reports of suspected rhabdomyolysis associated with rosuvastatin. Five of these were receiving the maximum 40mg dose.
But Dr Sidney Wolfe is worried that even the lowest dose, 10mg, carries too high a risk.
|
We need a clear assessment and advice from the licensing authorities on the safety and efficacy of this drug
Dr Jim Kennedy, prescribing spokesperson for the Royal College of General Practitioners |
He says the US has seen 20 cases of rhabdomyolysis and kidney failure in people taking 10mg of the drug.
"The renal toxicity, high rate of cases of rhabdomyolysis compared with other statins, and lack of unique benefit are compelling reasons to remove rosuvastatin from the market before additional patients are injured or killed," he says in his letter.
Dr Jim Kennedy, prescribing spokesperson for the Royal College of General Practitioners, said: "The reported incidents of the side effects of rhabdomyolysis and kidney damage with this drug are of concern and we need a clear assessment and advice from the licensing authorities [such as the CSM] on the safety and efficacy of this drug."
The CSM said: "As with other new medicines, the safety of rosuvastatin will continue to be closely monitored by the Medicines and Healthcare products Regulatory Agency and CSM.
"Should any new information or concerns regarding the safety of rosuvastatin emerge, the CSM and MHRA would take all necessary regulatory action.
AstraZeneca said Dr Wolfe's claims were "misleading" and based on inappropriate interpretation of data.
Dr Neil Brickel, the company's UK physician for Crestor, said Dr Wolfe had failed to look compare the number of cases with side effects with the rate of the drug used.
"The rate of side effects with Crestor is completely in line with other statins. Ten milligrams has been associated with some cases of rhabdomyolysis, but so has 10mg of the other statins as well.
"We are talking about a very rare side effect. The benefit-risk profile of Crestor is far in favour of benefit," he said.
Over-the-counter concerns
The warning intensifies doctor's concerns about patients soon being allowed to buy statins at pharmacies "over-the-counter" without the need of a prescription.
The British Medical Association is concerned about the safety and efficacy of statins being available over-the-counter.
From next month, another type of statin, simvastatin will be available over-the-counter as well as on prescription.
Dr John Chisholm, chairman of the BMA's General Practitioners Committee, said: "We are concerned that there won't have been a sufficiently thorough risk assessment before the drug is purchased.
"There are concerns about the risks of treatment as there are potential side-effects with all statins. Patients taking statins should be monitored on a regular basis to assess the effectiveness of the treatment."
Edit - lost the url above. Its http://news.bbc.co.uk/1/hi/health/3838915.stm
|
This message has been edited by SSRIAdmin on Nov 10, 2008 1:10 PM
This message has been edited by SSRIAdmin on Nov 10, 2008 1:03 PM
|
|
| AstraZ shares prices jump with joy
| TODAY the UK media pharma frenzy is how Crestor is good for healthy people ! | November 10 2008, 1:08 PM |
Google News
>>
Heart expert hails statins drug study
Belfast Telegraph, United Kingdom - 28 minutes ago
The UK's National Institute of Clinical and Health Excellence (NICE) recommends doctors carry out a risk calculation based on an individual's blood pressure ... |
 |
AstraZeneca gets boost from dramatic Crestor data
Pharma Times (subscription), UK - 1 hour ago
... and its impact on Crestor and indeed the whole company. Investors are certainly impressed and AstraZeneca shares were up 4% at £27.91 at 11am UK time. ... |
Statins drug trial success stuns docs
Glasgow Evening Times, UK - 1 hour ago
Yet those receiving medium doses of the drug, sold under the brand name Crestor, experienced far fewer adverse heart events than those given a non-active ... |
UK Stocks -- Factors to watch on Nov 10
Hemscott, UK - 5 hours ago
A study that showed AstraZeneca's cholesterol fighter Crestor slashed deaths, heart attacks, strokes and artery-clearing procedures in apparently healthy ... |
New! Get the latest news on uk crestor with Google Alerts.
This message has been edited by SSRIAdmin on Nov 10, 2008 1:11 PM
|
|
| 'The devil in the details' flushed out...
| The hailed CRESTOR "Jupiter trial" discussed by Professor Nortin Hadler | November 10 2008, 1:43 PM |
Dr. Nortin Hadler is professor of medicine and microbiology/immunology at the University of North Carolina at Chapel Hill, and an attending rheumatologist at University of North Carolina Hospitals. He is the author of Worried Sick: A Prescription for Health in an Overtreated America and The Last Well Person.
http://abcnews.go.com/Health/HeartDiseaseNews/story?id=6207285>
Crestor, by Jove... or Not
Doctor Urges Caution in Interpreting New Findings on Cholesterol Drug
OPINION by NORTIN M. HADLER, M.D.Nov. 10, 2008
On March 31, 2008, pharmaceutical giant AstraZeneca trumpeted the early closing of its so-called JUIPITER trial of a cholesterol-lowering drug (statin), Crestor. The results after only two years yielded "unequivocal evidence" of the drug's effectiveness, the trial concluded, and the company argued that it could not be withheld from anyone who was well and had normal cholesterol levels but had an elevation in another normal blood constituent, the C-reactive protein (CRP).
I am the skeptical physician who is unwilling to let anyone test my cholesterol until I see unequivocal data that taking a statin yields meaningful benefit for me. Now AstraZeneca wants me to get my CRP measured so that I can swallow Crestor if it's elevated.
On Nov. 9, 2008, the results of JUPITER were published in the online edition of the New England Journal of Medicine.
I knew there was a devil in the details. Let me flush it out for you.
AstraZeneca invested a great deal in this Herculean drug trial. They contracted with physicians in over 1,300 centers in 26 countries to recruit subjects. Some 90,000 were screened and nearly 18,000 enrolled.
At each center, half the recruits were randomly assigned to swallow a placebo pill, the other half Crestor. The intent was to monitor this army of volunteers for five years to see if the groups differed in their incidence of any of the following: heart attack, stroke, hospitalization for unstable angina or for surgery on their coronary arteries and death from cardiovascular causes.
JUPITER, as is true for all modern trials, had an oversight committee charged with breaking the code periodically to see if the volunteers on Crestor were fairing better or worse than the volunteers on the placebo. The JUPITER oversight committee comprised luminaries in the world of cardiology who, like nearly all the principal JUPITER trial investigators, had declared financial involvements with the industry that serves the cardiovascular enterprise, many with AstraZeneca.
After 1.9 years, the oversight committee sounded the alarm when they noted a highly statistically significant 56 percent reduction in the incidence of these feared outcomes. The trial was terminated; AstraZeneca trumpeted the benefit of Crestor and stockholders took notice.
A reduction of 56 percent is hard to ignore -- at first blush. It conjures up an image of marshalling 100 soldiers armed with Crestor and 100 not so armed to assault the cardiovascular monster for two years, at the end of which 56 of the Crestor soldiers are the only ones left standing.
If that were true, I'd have my CRP tested today. But that's not even close to truth.
At the end of two years, about 2 percent of study participants suffered a cardiovascular event. On Crestor, 1.6 percent suffered one of the cardiovascular events, whereas it was 2.8 percent of those not afforded Crestor -- a difference of 1.2 percent.
However, not all these people were in the trial all of the first two years; they entered at different times reflecting the vagaries of recruitment. A more accurate reflection that takes this into account is to calculate for every 100 how many would have suffered one of the cardiovascular outcomes in a year in the trial. This event rate for any of the events (the "composite outcome") is 0.77 on Crestor and 1.36 without Crestor.
That's the 56 percent reduction that is being trumpeted. That means I'd have to treat a hundred or more people with Crestor for a year to spare one of them a cardiovascular event that they would not have otherwise had. I'd have to treat several hundred for a year to spare one a heart attack, and perhaps hundreds more to spare one a stroke. I am unwilling to even suggest a life-saving benefit.
So the reduction of 56 percent may be hard to ignore, but it calls for reflection rather than prescribing zeal. It is a reduction in a very small outcome to an even smaller outcome. Consider these two questions:
 Are you convinced this small effect is real, that it will reproduce if one were to repeat the JUPITER trial?
I am not. I am reflexively skeptical of effects of this magnitude. My main reason relates to the nature of the randomized controlled trials we rely on for evidence. There are many factors vying to seal a well person's cardiovascular fate.
For example, there are the so-called cardiovascular risk factors such obesity and tobacco abuse. By assigning volunteers randomly to Crestor or placebo, one hopes that the number of smokers and obese folks are equal in the two groups.
When the JUPITER investigators checked, indeed such measurable risk factors were distributed 50-50. One has to have faith that the factors that cannot be safely measured (such as the degree to which the blood vessels are diseased) also distribute 50-50. And one has to have faith that the factors that JUPITER was designed to ignore distribute 50-50.
Socioeconomic status, job security, education level are even more important risk factors that are independent of those measured and likely to vary widely across the research sites in these 26 countries. Slight imbalances between the Crestor and placebo groups could result in effects of the magnitude touted by JUPITER.
I never leap to act on the basis of such small effects. It's why this year if you feed your family margarine, you're not a caring person and last year it was butter that was bad for you.
If you're convinced these small effects are real, are they meaningful to you?
Are you willing to swallow Crestor every day for two years in the hopes you're the one in hundreds who just might be spared a non-fatal heart attack? Does it bother you that more of the volunteers on Crestor were diagnosed with diabetes?
This possible association aside, there is nothing to suggest that the volunteers for JUPITER were harmed in the two years. But that does not mean the drug is risk-free. Does it bother you that the occasional person on Crestor develops a muscle disease, or that some have liver or kidney irritation?
I am not tormented by such uncertainties as I doubt the small effects are real and therefore have no interest in taking Crestor. You and your prescribing physician should take pause, at the very least.
Small Effect, Big Benefit? Debate Continues
However, the JUPITER investigators and AstraZeneca do not share my concerns. Rather they take refuge in several of the tenets of contemporary small-effect epidemiology. They believe that these small effects are real.
Furthermore, they believe that the small effects recognized in the first two years are likely to prove cumulative and therefore grow as the years pass. It's this belief that triggered the halting of the trial.
And finally they believe that the small likelihood of a good effect for an individual translates into a major public health benefit; benefiting one in a hundred means benefiting 1,000 in every million.
Therein lays a heated academic debate and an important philosophical conundrum. As for me, I won't let you check my CRP either.
Dr. Nortin Hadler is professor of medicine and microbiology/immunology at the University of North Carolina at Chapel Hill, and an attending rheumatologist at University of North Carolina Hospitals. He is the author of Worried Sick: A Prescription for Health in an Overtreated America and The Last Well Person. "
|
| | Current Topic - The NOT so "fantastic" side of CRESTOR despite sudden UK media push on behalf of AstraZ |
| |
|
|
