Front-page headlines worldwide announced the “stunning” results of a trial of rosuvastatin (Crestor) in “apparently healthy men and women” with an LDL-cholesterol less than 130 mg/dL (3.4 mmol/L). Serious heart problems were reportedly reduced by about 50%.
“This takes prevention to a whole new level,” said Dr. W. Douglas Weaver, President of the American College of Cardiology (Washington Post 11/10/08).
The trial, called JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) was financially supported by AstraZeneca, the manufacturer of Crestor. It is not stated whether the trial was named before or after data were accumulated. The primary author, Paul Ridker, also is listed as a coinventor on patents for the use of inflammatory biomarkers, including the use of high sensitivity C-reactive protein (HS-CRP) in the evaluation of risk for cardiovascular disease.
The 17,802 subjects in the trial had an elevated HS-CRP of 2.0 mg/L or higher (Ridker PM, et al., N Engl J Med 2008;359:2195-2207).
Until Nov 26, the New England Journal of Medicine is inviting comments on whether this article will change your practice.
As the accompanying editorial noted, the absolute risk reduction was low. The number (percent) of “hard” outcomes (myocardial infarction, stroke, or death from cardiovascular causes) was reduced from 157 (1.8%) in the placebo to 83 (0.9%) in the rosuvastatin group. The number needed to treat was 120. The cost of the drug is $3.45 per day (or nearly $300,000 to prevent one adverse event).
Note that the trial evaluated statins, not HS-CRP testing. It did not compare subjects with and without high HS-CRP, nor compare the usefulness of HS-CRP with other risk factors (ibid.).
On the adverse side of the balance, subjects in the rosuvastatin group had significantly higher glycosylated hemoglobin levels and incidence of diabetes mellitus (3.0% vs. 2.4%) (ibid.) The trial was discontinued three years early, after only 1.9 years, thus cutting off the discovery of potential long-term adverse effects.
While not yet statistically significant, the rosuvastatin group had more muscle weakness and pain and more elevations in laboratory values indicating possible kidney or liver damage. One case of nonfatal rhabdomyolysis was reported in a rosuvastatin recipient after the trial was suspended. During a 4-week run-in period, anyone exhibiting compliance problems or adverse reactions could be screened out; 1,521 subjects were excluded during this period, in addition to the nearly 57,000 eliminated at the outset. Compliance rates during the trial were unusually low, with nearly 15% of the participants stopping their pills during each year, noted Sandy Szwarc, B.S.N., R.N.
What the JUPITER study really shows, remarks Duane Graveline, M.D., M.P.H., is that statins work by reducing inflammation, not by reducing cholesterol. This effect requires much lower doses, which have fewer side effects.
While rates of hospitalization for coronary heart disease have shown decreases since the mid-1980s, the rate for congestive heart failure has increased continually since 1980. From 2002-2006, the relative risk of hospitalization for heart failure was 1.37 times the rate in 1980-1984, according to research presented at the American Heart Association’s 2008 scientific session (Medical News Today 11/12/08).
Additional information:
- “The Failure of Vytorin and Statins to Improve Cardiovascular Health: Bad Cholesterol or Bad Theory?” by Brian Peskin, et al. J Am Phys Surg, Fall 2008.
- “Misleading Recent Papers on Statin Drugs in Peer-Reviewed Journals,” by Joel Kauffman, Ph.D., J Am Phys Surg, Spring 2007.
- “LDL Cholesterol: ‘Bad’ Cholesterol or Bad Science?” Anthony Colpo, J Am Phys Surg, Fall 2005.
It is always amazing to me that educated people fall for such nonsense. The study was flawed and incomplete. If such a faulty study was published on a subject such as prolotherapy, we would hear these same esteemed colleagues screaming from the rafters. It ’s simply a drug company attempting to cloud the issue and find something good about very bad drugs.
It is nothing short of ridiculous that a number-needed-to-treat of 120 is considered acceptable. The authors claim that this goes down to 25 in 5 yrs.–but then they didn’t continue the trial for 5 yrs., so the claim is purely theoretical. I would consider an NNT of 25 to be too high even without the increased rate of diabetes (a relative 20% if my figures are correct). It is another example of Big Pharma attempting to convince physicians to NOT think. I just attended an internal medicine meeting at a Big 10 University where the first lecture was all about how wonderful statins are and how terrible it is to have any cholesterol at all, and the speaker quoted NNTs of 15-25 WITHOUT NAMING SOURCES which I am sure is just more extrapolated nonsense.
I’ll take my $300,000 in cash.
I agree with most of the comments above. The most striking statistic is the 50% risk reduction, when in fact the reduction was merely 1.8% to .9%. Such statistical gyrations to prove the efficacy of a drug are legion and are used to market every drug including those without practical therapeutic value. The most famous thus far were Nissan’s claims regarding Rosoglitasone and the Woman’s Health Initiative concerning the dangers of postmenopausal estrogen therapy.
I heard Dennis Prager on the radio recently singing the praises of statins, based on JUPITER. He’s a true believer, as he was in Seth Roberts’ Shangri-La Diet. He doesn’t do medical shows often, which is good. He doesn’t have a good track record in this area, as smart as he is.
Assuming the study results are valid – and I’m not sure they are – SOMEONE is going to have to decide how much should be spent to prevent ONE stroke, heart attack, or death over the course of two years. For an individual, the cost of the drug alone is $2500 (US) for two years. And after the two years is up, your PCP is going to recommend you keep taking the drug for the rest of your life.
$2500 is an expensive insurance policy. Many individuals would choose to forego the expense and take their chances, perhaps working instead on lifestyle modification. E.g., stop smoking, lose the excess weight, switch to a traditional Mediterranean diet, exercise regularly.
On the other hand, many people would be happy to pop the pill as long as someone ELSE is paying, like their employer, the taxpayers, or their health insurer.
-Steve
So the circle is complete. The modern snake oil salesmen. Or drug company whore. There mama’s would be proud.
I agree that this is just more hype by the pharmceutical industry. No one has ever demonstrated that cholesterol is harmful. In fact cholesterol is a vital and important part of building cell membranes. So Jupiter has demonstrated what we’ve know for years i.e. inflammation produces the conditions favorable to heart attacks. That’s why studies using antibiotics have shown reductions in myocardial events. The best solution to the inflammation problems is high dose(3g for everyone and 5g for those with heart disease) omega-3 fish oil. The original Eskimo diet was loaded with fat and they had practically no heart disease. The real importance of fat in the diet is only just beginning to be told. Statins affect your memory, muscles and liver. If you want to spend your money wisely, invest it in good fat and enjoy.
It appears that journalists have a short memory.
Only four year ago, Dr. David Graham, associate director in the FDA’s Office of Drug Safety gave senate testimony that Crestor was one of five drugs with safety concerns. The drug causes muscle breakdown and renal failure.
To read more…
http://jeffreydach.com/2008/11/14/crestor-jupitor-crp-and-heart-attack–by-jefffrey-dach-md.aspx
Jeffrey Dach MD
I agree that Crestor and it’s ilk do have serious safety concerns.
Seeing such symptoms muscle breakdown and renal problems in real time in my new patients on these is startling.
Such massive marketing and prescribing of any drug raises a monstrous red flag.
Just try to get a new outlet to interview you on such, very difficult
More terrifying is the HPV vaccine.
What do you think?
Facts Believed to be Associated With All Statin Medications:
Adverse events associated with the statin class of pharmaceuticals are thought to occur more often than they are reported- with high doses of statins prescribed to patients in particular. However, ince this class of drugs has existed for use for over 20 years, statins are considered safe and effective for enhancing the clearance of LDL noted to be elevated in the lipid profiles of patients.
Additionally, there is no reduction in cardiovascular morbidity or mortality, as well as an increase in a person’s lifespan, if one is on any particular statin medication for their lipid management over another, others have concluded. So caution should perhaps be considered if one chooses to prescribe such a drug for a patient if they are absent of dyslipidemia to a significant degree, or are under the belief that one statin medication provides a greater cardiovascular benefit over another. In other words, the health care provider should be assured that any statin therapy for their patients is considered reasonable and necessary if the LDL in their patients need to be reduced perhaps at this time with the evidence that exists regarding statins.
Abstract etiologies for those who choose to prescribe statin drugs on occasion for reasons not indicated by these statin drugs- such as reducing CRP levels, or for Alzheimer’s treatment, or anything else not involved with LDL reduction may not appropriate prophylaxis at this point for any patient. All other benefits that appear to have favorable effects in such areas are speculative at this point, and require further research for disease states aside from dyslipidemia, according to many.
Statins as a particular class of drugs that seem to in fact decrease the risk of cardiovascular events significantly, it has been proven. Statins also decrease thrombus formation as well as modulate inflammatory responses (CRP). For those patients with dyslipidemia who are placed on a statin, the effects of that statin on reducing a patient’s LDL level can be measured with the efficacy of the statin after about five weeks of therapy on a particular statin drug. Liver Function blood tests are recommended for those patients on continued statin therapy, and most are chronically taking statins for the rest of their lives to manage their lipid profile in regards to maintaining the suitable LDL level for a particular patient presently.
Yet some have said that about half of all strokes and heart attacks that do occur are not because of increased cholesterol levels of these patients. Others believe that it is oxidized cholesterol that causes vulnerable plaques to form on coronary arterial walls, which is the catalyst for a heart attack, and that there is no medicinal treatment for the formation or stabilization of these plaques to prevent heart attacks or strokes. Others who promote and support statin medicinal therapy claim that these drugs, do, in fact, stabilize these plaques, and therefore are beneficial.
As stated previously, in regards to other uses of statins besides just LDL reduction, there is evidence to suggest that statins have other benefits besides lowering LDL, such as reducing inflammation (CRP) with patients on statin therapy, those patients with dementia or Parkinson’s disease may benefit from statin medication, as well as those patients who may have certain types of cancer or even cataracts. Yet again, these other roles for statin therapy have only been minimally explored, comparatively speaking. Because of the limited evidence regarding additional benefits of statins, the drug should again be prescribed for those with dyslipidemia only at this time involving elevated LDL levels as detected in the patient’s bloodstream.
Yet overall, the existing cholesterol lowering recommendations or guidelines should be re-evaluated, as they may be over-exaggerated upon tacit suggestions from the makers of statins to those who create these current lipid lowering guidelines. This is notable if one chooses to compare these cholesterol guidelines with others in the past. The cholesterol guidelines that exist now are considered by many health care providers and experts to be rather unreasonable, unnecessary, and possibly detrimental to a patient’s health, according to others. Yet statins are beneficial medications for those many people that exist with elevated LDL levels that can cause cardiovascular events to occur because of this abnormality. What that ideal LDL level is may have yet to be empirically determined.
Finally, a focus on children and their lifestyles should be amplified so their arteries do not become those of one who is middle-aged, and this may prevent them from being candidates for statin therapy now and in the future, regarding the high cholesterol issue.
Dietary management should be the first consideration in regards to correcting lipid dysfunctions,
Dan Abshear