- About
- Blogosphere Buzz
- Archived Posts 2007-2008
- Register for Email Alerts
- The Book: Before You Take That Pill: Why the Drug Industry May Be Bad For Your Health
- Follow me on twitter @dougbremner
- Subscribe to my podcasts
- Rave Reviews for “The Goose That Laid the Golden Egg: Accutane, the truth that had to be told”
- Follow me on goodreads
Mrs. Bremner [DOCTOR BREMNER to YOU guys!] is attending the Annual Meeting of the American Heart Association this week in New Orleans and texted me some news about the release today of results from the JUPITeR study (“Justification for the Use of statins in Prevention: an Intervention Trial evaluating Rosuvastatin (JUPITeR)”) published in the New England Journal of Medicine
.
(gasp), Oh really. I think this one would definitely not have been a turn on for Aphrodite.
Ha, ha.
Based on the results of this study, that a biomarker of heart disease, C-reactive Protein (CRP), predicts response to the drug Crestor (rosuvastatin) (and not just total cholesterol or LDL cholesterol), the authors of this study would apparently like us to come to the conclusion that, basically, all of us should be on a statin medication for the prevention of heart disease. In fact, I can already hear the shills and the media saying “revolutionary” and “likely to change practice”! In fact there is even a cheesy site on the New England’s website asking us how it will change our practices (gasp, shame).
We’ve been through this drill before, when our country’s “leading” cardiologists informed us that statins were so great that they should be put in the drinking water.
But now, let us turn our attention to the results of the JUPITeR trial.
17,802 healthy men and women with LDL cholesterol of less than 130 mg per deciliter and CRPs of greater than 2.0 mg per liter were given either rosuvastatin 20 mg per day or placebo. They were then followed for the occurrence of the “combined primary endpoint” of heart attack, stroked, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes.
First of all, whenever doctors start combining real disease outcomes (like dying of a heart attack) with what are primarily… er… inconveniences, like going to the hospital, you have to start wondering about the study.
OK. So what about the results, you say. For their primary outcome out of 100 people treated each year there were 0.77 versus 1.36 who had an event like heart attack, hospitalization, etc. That is a difference of 0.59%. But I am going to ignore their cheesy primary endpoint and look at what to me matters, which is heart attacks. 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 a difference of 0.2%, which would have amounted to a 1% difference over five years if the study had continued for that long, but the study committee cheerfully “stopped” the study after 1.9 years since they thought things were going so well that it would be “unethical” to continue the study (Hooray!).
I guess that 1% of responders outweighs the 3% or so that will develop liver toxicity or muscle damage.
Study results that will change clinical practice, indeed.
BTW, look at the end of the article for the long list of consulting agreements to the pharmaceutical industry engaged in by the authors of the study. And funding by AstraZeneca.
[originally posted November 10, 2008]
COMMENTS
Viola Vaccarino wrote on November 10, 2008
The study excluded subjects with diabetes or hypertension and there was a four week “placebo” run in phase and subjects who were not compliant during that phase were dropped. 80% of the patients were excluded and many more were excluded during the placebo run in phase. What this means for the regular patient is unknown.
Marilyn Mann wrote on November 10, 2008
Just read this. Wondering why you did not mention 20% reduction in total mortality. Also interesting that women benefited to the same extent as men.
See studies published ahead-of-print yesterday in Circulation and Circulation Cardiovascular Quality and Outcomes for more info on CRP.
C-Reactive Protein and Parental History Improve Global Cardiovascular Risk Prediction. The Reynolds Risk Score for Men Paul M Ridker, Nina P. Paynter, Nader Rifai, J. Michael Gaziano, and Nancy R. Cook Circulation published 9 November 2008, 10.1161/CIRCULATIONAHA.108.814251
C-Reactive Protein and Reclassification of Cardiovascular Risk in the Framingham Heart Study Peter W.F. Wilson, Michael Pencina, Paul Jacques, Jacob Selhub, Ralph D’Agostino, and Christopher J. O’Donnell Circ Cardiovasc Qual Outcomes published 9 November 2008, 10.1161/CIRCOUTCOMES.108.831198
Doug Bremner wrote on November 10, 2008
The reduction in total mortality was 1.0 per 100 patient years versus 1.25 in the placebo group, a difference of 25% in relative risk, but of 0.25% in absolute risk (i.e. not that great). I think one thing this study highlights is that maybe LDL reduction is not the “cause” of risk reduction, or at least exclusively.
The other issue is what the clinical implications of this study are. Are doctors going to check CRP and LDL in everyone and treat whoever fits either profile? That means everyone will be on this stuff. Crazy.
David Diamond wrote on November 10, 2008
Doug – great commentary on the Jupiter trial and kudos to you for your muckraking blog
the whole statin revolution seems driven by big pharma greed with little real benefit to the population, followed by sheep-like docs who can’t see the flaws in the research
can you imagine turning the CHD word upside down by showing better CHD outcomes with a diet low in sugar and high in chocolate vs a statin?
Odysseas wrote on November 10, 2008
Again, I think people get so enamored by the relative risk that they dont even consider the difference in absolute risk or the NNT… (The calculation may be useful for some readers) As the fanfare dies down, perhaps a thoughtful discussion will ensue..
Doug Bremner wrote on November 10, 2008
Yes, the relative risk v absolute risk distinction is critical. The story I use is for primary prevention in men with risk factors. Out of 100 men, 4 men on placebo will have a heart attack in five years v 3 on a statin. If you told someone that a drug would reduce his risk of having a heart attack by 25% (and told him none of the risks, he would take it! If you went into a room of 100 men and said I want you all to take a drug and it will prevent only one of you from having a heart attack, but three of you will have some liver damage or muscle pain, and maybe it causes cancer but we are not sure, they wouldn’t take it. Both describe the same situation (going from 3 to 4 is a 25% change (relative risk) but 4%-3%=1%). Crucial distinction. Most doctors don’t understand, but the pharma detail people do. And they always use the one that suits them best. Also, NNT is the number needed to treat. Means that (in this case) 31 patients need to be treated for four years to save one from a cardiovascular event or procedure (their primary outcome). Which isn’t all that great. The authors pointed out that this is similar to prior studies of those with high LDL, but all that says is that LDL is not the be all and end all (the cardiology research community has been moving toward the inflammatory pathways area for several years now; elevated CRP is probably associated with the metabolic syndrome, etc).
Thanks for making these important points. They deserve a press story.
Mathew? Caleb? Anyone?
David dcsciencewrote on November 11, 2008 on his blog
Here is a link to a discussion of should we all take statins and relative versus absolute risk
[David is currently discussing creationism; recommended blog for fans of science and skepticism]
Therapy Patient wrote on November 12
I groaned when I heard that report on NPR today and was disappointed none of the interviewed doctors mentioned muscle and liver problems. My Dad was one with muscle pain and weakness and a deteriorating liver but his cardiologist insisted he stay on the drug. Dad stayed on the drug and Dad died. Well he was 90 and had a host of problems, so who is to say what killed him? The autopsy listed a long list of problems. I take a statin, that’s for sure!
With statins as a class of medications: A.E.s are often under-reported with high doses of potent statins in particular. Additionally, there is no reduction in mortality or increase in the lifespan with those on statin therapy.
Dan Abshear wrote on November 12
Several risk factors should determine if one is placed on statin therapy, and not just one. Statins do decrease CV events and risks significantly.
The meds. increase endothelial function, stabilize coronary plaque build up, and decrease thrombus formation. Maximum reduction in LDL is evaluated after about a month of therapy from any particular statin. There is evidence to suggest that statins have other benefits besides lowering LDL, such as reducing inflammation (CRP), those with dementia or Parkinson’s disease, and some forms of Cancer and cataracts. It appears those statins produced by fermentation, such as Zocor and Pravachol, have less myopathy than the other synthetic statins, possibly due to being more hydrophyllic. Yet overall, the existing cholesterol lowering recommendations should be re-evaluated, as they may be over-exaggerated. With children, diet needs to be controlled with them so they do not develop arteries of one who is middle age and a possible candidate for statin therapy,
Dan Abshear
If you enjoyed this article, please consider sharing it!
Part II:
Facts Believed to be Associated With All Statin Medications:
Statins are a class of medications specifically prescribed to lower LDL- one of five lipid parameters of a person’s lipid profile. There are 6 available statins to choose- with three that are combination drugs that have a statin as a component of these medications. There are other classes of medications for lipid management, such as bile acid sequestrants and nicotinic acid, which is known as niacin. Yet the side effect profile is more unfavorable of these classes of medications compared with the statin class.
One’s cholesterol level is primarily due to how they produce cholesterol in their liver, which is overall genetically determined. This level is also determined by one’s lifestyle and diet as well. If a person has too much cholesterol in their blood, it can lead to hardening and narrowing of their arteries, which can lead to cardiovascular events.
To measure one’s cholesterol, a blood test called a lipid profile is obtained from a person after they have fasted for at least 12 hours. The test should also be performed only if the person is free of any acute illness, as this may affect true lipid measures. If the results prove to be abnormal, lipid lowering therapy may be initiated, according to the discretion of the person’s health care provider. This therapy usually involves a statin medication.
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 at times that may not be necessary to control their dyslipidemia based on their lipid profile. However, since 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. Also, they have proven to reduce cardiovascular mortality with one who is treated with a statin that has dyslipidemia. In addition to lowering LDL by up to 60 percent- depending on the statin- this class of drugs also raises HDL and lowers triglycerides, which are two other lipid parameters. Both of these effects from taking a statin drug are beneficial for the patient on a statin drug for lipid management.
Statin therapy is also recommended for those patients who have a greater than twenty percent risk of developing cardiovascular disease, or those patients that have clinical evidence of this disease
Additionally, there appears to be no comparable reduction in cardiovascular morbidity or mortality, as well as a difference in the increase of one’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 a statin for a patient if they are absent of, or have only mild dyslipidemia to a significant degree. Furthermore, research should be done by the health care provider if they 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 choice of statin therapy for their patients is considered reasonable and necessary if the LDL in their patients need to be reduced, and the statin selection should be determined by the results that have been shown with a particular statin.
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 with prevention if not delaying the progression of cardiovascular disease, should be thoroughly evaluated by the health care provider. As statin therapy for such patients may not be considered appropriate prophylaxis at this point for any patient who does not have the indications for which statins are approved for and treat with patients. All other benefits that appear to have favorable effects in such areas are speculative at this point due to minimal research in other areas aside from lipid management, and require further research for these 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) as additional benefits of the medication. 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 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. Patients should be made aware of potential additional side effects as well, such as muscular issues.
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 primarily LDL reduction, there is some evidence to suggest that statins have other benefits besides lowering LDL. These other disease states include aside from what has been stated already, those patients with dementia or Parkinson’s disease, 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 statin medications, 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 possibly 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. Treating children with a statin drug for dyslipidemia is controversial presently.
Dietary management should be the first consideration in regards to correcting lipid dysfunctions that may exist in patients,
Dan Abshear