Doc Gumshoe’s News: Some Good, Some Not So Good

By Michael Jorrin, "Doc Gumshoe", January 5, 2015

[ed note: Michael Jorrin, who we like to call “Doc Gumshoe”, is a longtime medical writer (not a doctor) who writes non-investment articles about medicine and health topics for us once or twice a month. As with all of our guest contributors and columnists, he chooses his own topics and his words are his alone]

In a recent New Yorker, a rapturous write-up of an Indian restaurant on the upper West Side of Manhattan (Awadh, on Broadway at 98th Street) concluded with these words: “At the end of such an extravagant meal, it’s hard not to feel as if one has imbibed a pound of melted butter and a quart of cream. But, as you may have heard, the medical establishment now says that butter is good for you, or, at least, not bad for you. We concur.”

Doc Gumshoe can’t possibly know what Shauna Lyon, the writer of the New Yorker piece, had in mind with that assertion, but here are some possibilities:

  • One, she’s aware of the now widely-accepted premise that only about 15% to 20% of the cholesterol in our bodies entered as cholesterol. We synthesize most of it from a variety of things we eat, and synthesize it we must, because cholesterol is essential for life.
  • Two, she has paid attention to the increasing emphasis on the effects of total diet on heart disease risk, with special attention to transfats, salt, and sugar as menaces, and less emphasis on the old bugaboos such as butter, eggs, and cream.
  • Three, she has noticed that, according to the recent guidelines promoted by a couple of influential medical societies, people are recommended to start taking statins mostly on the basis of risk factors, and once they’re on statins, their cholesterol levels are no longer monitored. So, if cholesterol isn’t being monitored, why worry about trifles like an extra pound of butter and a quart of cream?

No matter. Underlying this speculation is an uncertain state of affairs when it comes to the overall management of cardiovascular risk factors. The definitive formula has yet to be derived, even though guidelines and recommendations keep being issued. Doc Gumshoe readers may remember my comments on the new statin guidelines, which were promulgated by the American College of Cardiology and the American Heart Association (ACC/AHA) about a year ago. (If you missed it, you can check it out here.) Here’s a quick summary of those guidelines:

  • They attempt to quantify total cardiovascular risk by arriving at a percentage figure for a ten-year risk of cardiovascular events (heart attack or stroke), based on an algorithm. Individuals aged 40 – 75 whose ten-year risk is 7.5% or higher are recommended to take statins.
  • They recommend that persons whose LDL-cholesterol levels are 190 mg/dL or higher should take statins.
  • They also recommend that all persons with existing heart disease or Type 2 diabetes should take statins.
  • However, specific LDL-cholesterol goals are not part of the new guidelines. According to the guidelines, regular monitoring of blood cholesterol levels is not necessary, and the effects of treatment should not be based on how much cholesterol-lowering takes place.

It was estimated that implementing these guidelines would result in 70 million people in the US being on statins.

The ACC/AHA guidelines were immediately criticized, on a number of grounds, by some of the most eminent cardiologists in the land. I do not know how widely they have been put into practice.

So, keep those guidelines in mind while we quickly review a new study that sheds interesting light on the whole question of managing cardiovascular risk.

IMPROVE-IT: Not huge news, but definitely provocative…

This was a large, long study of a drug that a lot of practitioners didn’t have much confidence in. The drug was ezetimibe (Zetia), given in a combined formulation with simvastatin, and marketed by Merck as Vytorin. The study, whose results were made public at the American Heart Association 2014 Scientific Meetings this past November, enrolled 18,144 high-risk patients within 10 days after they had sustained an acute coronary event such as a heart attack (myocardial infarction or MI) or a stroke. Baseline LDL-cholesterol levels in all patients in the study were quite low, in most cases 100 mg/dL or even lower.

Patients were assigned either to a statin alone or to the ezetimibe-simvastatin combination, and followed for six years, until there had been 5,250 primary endpoint events in the trial, those being cardiovascular death, MI, stroke, or hospitalization for acute coronary events. The results of the study were by no means a huge home run for the Vytorin combo, but they were significant in more ways than one.

Patients on the combined ezetimibe-simvastatin combination had 13% fewer MIs, 14% fewer strokes, and 21% fewer ischemic strokes than patients who were on a statin alone. (Note: these were relative risk reductions, not reductions in the absolute risk.) Differences in other endpoints were minor, and there was no difference in cardiovascular deaths.

Are you getting our free Daily Update
"reveal" emails? If not,
just click here...


In the context of our discussion about guidelines, however, one of the most interesting results was that at the conclusion of the study, the mean LDL-cholesterol level in the statin alone group was 69.9 mg/dL, while in the ezetimibe-simvastatin group the mean LDL-C level was 53.2 mg/dL.

This suggests (but does not prove!) that a reduction in LDL-C of about 15 mg/dL from an already quite low level resulted in real and significant clinical benefit in terms of lowering the rate of acute coronary events.

A hole in the ACC/AHA guidelines

The ACC/AHA guidelines explicitly state that continued monitoring of cholesterol levels is not needed once a patient is put on a statin regimen. Yet here we have a study in patients, all of whom are on statins, where a difference in LDL-cholesterol results in important clinical benefit. How can that difference in LDL-C be attained without cholesterol monitoring? How can the clinicians track what’s going on with patients if they don’t measure the cholesterol levels?

And, just as important, what keeps patients adherent to treatment if there aren’t markers to let them know how they’re doing?

The thrust of the ACC/AHA guidelines is to reduce the focus on the lipid levels and pay increased attention to the other risk factors. Clearly, those other risk factors are important. But the IMPROVE-IT study actually told us something we really didn’t know before, specifically that lowering LDL-C to levels considerably below those previously thought to be optimal, even in high-risk patients, delivers real benefits.

How is ezetimibe different from statins?

In a nutshell, ezetimibe takes aim at that pound of melted butter and quart of cream that you ingest at that Indian restaurant. What it does, with moderate effectiveness, is prevent the cholesterol in that butter and cream (and also in the filet mignon and foie gras that you wolf down at the French restaurant) from passing through the walls of your small intestine and making its way into your bloodstream. Statins, in contrast, inhibit cholesterol synthesis, so teaming up the inhibitor of cholesterol transport with the inhibitor of cholesterol synthesis would seem to make good intuitive sense.

The flaw in this proposition is that, in most people, under most circumstances, most of the time, dietary cholesterol contributes to at most 15% to 20% of our total circulatory cholesterol. Therefore, ezetimibe isn’t ever going to result in big cholesterol reductions.

I suspect that when ezetimibe was in the very earliest stages of investigation as a potential cholesterol-lowering drug, the general assumption in the medical community was that our circulating cholesterol entered our bodies in the obvious form – cholesterol-rich foods – and if a way could be found to block that means of entry, it would be a huge boon. But by the time it hit the market, the statins had gotten there first and demonstrated genuine benefits in terms of cardiovascular survival. Ezetimibe didn’t make much splash. Novartis (the developer) has mostly been marketing ezetimibe, under its trade name Zetia, to patients who develop those troublesome statin-related muscle aches termed rhabdomyopathy, or in extreme cases, destruction of muscle tissue, termed rhabdomyolysis.

What will IMPROVE-IT achieve?

My guesses:

First, it will put the focus back on regular tracking of cholesterol levels, at least in patients with cardiac risk factors, and likely in most patients who have regular check-ups.

Second, it will re-validate the premise that there is a close and causal link between cholesterol levels and cardiovascular events.

Third, it will put a stake in the ground for the argument that lower LDL-C levels, lower even than the target levels in many guidelines, will confer clear benefit in terms of cardiovascular risk reduction. The target LDL-C level for high-risk patients, such as those with diabetes, is 70 mg/dL, but this has been very difficult to achieve with the available drugs to date.

Fourth, it will once again put dietary cholesterol in the cross-hairs of the health-care establishment, since it seems evident that the risk reductions demonstrated in IMPROVE-IT came about through preventing the absorption of dietary cholesterol.

Will it catapult Vytorin into the ranks of top-selling cardiac drugs? We’ll see.

But I wouldn’t be surprised if the greatest economic benefit of the study accrues to the PCSK9 inhibitors that are coming along, since they also produce very large reductions in LDL-cholesterol. At this moment, Amgen, Regeneron, and Pfizer are in that race, in that order.

PCSK9 inhibitors reduce LDL-C through an entirely different mechanism. What they do, in a nutshell, is reduce the activity of certain proteins (PCSK9s) which, in turn, block the LCL-C receptors whose function it is to remove LDL-C from the bloodstream. So, blocking those PCSK9 proteins restores the function of the LDL-C receptors and permits them to do their job.

So, is this good news?

Doc Gumshoe gives this a big yes. The data points in a good direction, namely, further reductions in cardiac events. This comes on top of the huge gains in managing cardiovascular disease that have already been notched. For example, the American Heart Association estimates that if cardiovascular mortality in the US had remained at its peak level, which happened in the mid 1960s, almost 12 million more of us would have died of heart disease since 1995, when the rate really started to go down.

… and now for some not-so-good news …

Let’s save the good news for later. This news item is more than an item, and it has truly global implications. The lead-in was an article in the NY Times datelined Amravati, India, which reported that 58,000 newborn babies in India died of infections which were resistant to any known antibiotic. The article went on to mention that this was only a fraction of the 800,000 newborns who die annually in India, representing about one-third of the annual newborn deaths in the entire world.

That’s bad enough. But then it went on to say more about the circumstances. It seems that nearly all newborns in India are routinely given antibiotics, whether they’re born with infections or not. The reason for this is that the assumption among health providers in India is that just about everything that these infants come into contact with is loaded with pathogens, starting with their mother’s genital tract. The root of the problem is probably that about half (the official estimate is 600 million) of Indians defecate outdoors, and that pathogens are pervasive in water, sewage, and soil. As a result, Indians have the highest rate of bacterial infections in the world, and also the highest rate of antibiotic consumption. Antibiotics are sold cheaply over the counter.

The source of most antibiotic-resistant infections in newborns is hospitals. The Indian government has a program that encourages mothers to give birth in hospitals, and currently about 82% of babies in India are born in hospitals. However, hospital facilities are inadequate: a UNICEF survey of district hospitals in one region found that 70% had contaminated water and 78% had no soap available at hand-washing sinks.

The response has been to inject newborns with antibiotics routinely, whether they show signs of infection or not.

This, of course, multiplies the prevalence of resistant pathogens, and constitutes a serious threat to the entire population of India, and other regions as well. One particular “superbug,” the New Delhi metallo beta-lactamase 1 or NDM1, has already been identified in France, Japan, and the US.

But there’s another way this affects us …

Yes, antibiotic resistance is an old story. Doc Gumshoe did a piece about that back in October of 2013, but that piece didn’t dwell on a particular aspect of the story that is highly troubling: it becomes increasingly apparent that the pharmaceutical industry is not eager to invest in developing the kinds of antibiotics that might be effective against some of the current generations of resistant pathogens.

Let’s briefly consider the antibiotic development process. First, a class of pathogens is identified that is causing disease and is resistant to treatment. Then researchers find a way to foil the mechanism through which the pathogen escapes the effects of previous drugs, and come up with a new drug that gets around that mechanism in some way. Then comes all the testing for safety and efficacy, and the drug is compared with existing treatment options, and may finally find its way to the market. Currently, this costs upward of a billion dollars.

Then, what happens? The new drug is held in reserve for when it’s absolutely necessary. It’s not used routinely, because the consensus in the medical community is that routine use of this wonderful new drug would quickly lead to the emergence of a new generation of resistant pathogens, and render the new drug much less useful.

In some cases, the new miracle drug would only be used when the pathogen was positively identified as being a resistant strain. In some cases, it might be given “empirically,” which is to say, based on strong suspicion that the suspect pathogen is indeed resistant. This might happen in a particular community, where it is already known that a particular resistant strain has already infected other people, and the physician doesn’t want to wait for positive identification of the bug while the patient gets worse.

But the new miracle drug would not be used routinely whenever a patient presents with an infection which might possibly be due to a resistant bug.

So this new miracle antibiotic, which the pharma outfit spent more than a billion bucks to bring to the market, doesn’t exactly fly off the shelves.

A way around this conundrum has been proposed: offer generous prizes to pharma companies that develop antibiotics that work against resistant bugs, so that there’s an incentive to invest in drug development regardless of whether the drugs reaps a profit in the market.

My comment on that proposal is that the prize would have to be colossal. It would need to cover the complete cost of developing the antibiotic and taking it all the way through the clinical trials that demonstrated that it really did what it was supposed to do. And it would need to be enough to make it worth the risk the pharma companies would be taking in developing the drug and having it not be a winner.

So, on balance, Doc Gumshoe is squinting skeptically at the prize concept.

However, wait – here’s something else. You’re asking, what about those poor folks in India (and elsewhere), where these resistant pathogens are so common? Wouldn’t they want to get this new miracle drug?

You bet they want it, and indeed, they do get the new miracle drug. But mostly, the pharmaceutical company that developed it doesn’t get much revenue. Either they strike a deal to supply the drug at a special low price, or an Indian generic drug maker copies the basic molecule and sells it cheaply. When the originator pharma sues for infringement of patent, chances are they lose. The courts hold that humanitarian interests trump patent rights, and the pharma is out of luck.

And so, pretty soon, that drug doesn’t work either, because it has been overused, and pathogens resistant to the new miracle drug have emerged, making the whole effort a vain exercise.

The only solution to this problem that I can envision is that there be an effective global effort to restrict the use of such new antibiotics as may be developed to individual cases where they are genuinely needed. Widespread, routine, indiscriminate use of antibiotics as a substitute for effective public health and sanitation (as in India) needs to end. And, indeed, the Indian government announced a plan to “clean the country and build toilets.” This will not happen quickly. And in the meantime, antibiotic overuse continues to grow as a global threat.

More about PSA screening for prostate cancer

This is a confusing and controversial topic, but here goes, anyway. As we’ve discussed before in these blogs, the U. S. Preventive Services Task Force (USPSTF) specifically does NOT recommend PSA (prostate-specific antigen) screening for all men, because of the perceived likelihood that it will lead to overdiagnosis and overtreatment. What they mean by this is that, yes, screening will detect prostate cancers, but many of those men don’t really need to be treated, because something else will kill them first; also, treatment for prostate cancer is not without adverse effects — in particular urinary incontinence and impotence.

My view, which I have expressed at length in a previous blog, is that PSA screening is just a first step in a process. (You can check it out here.) No specific PSA cut-point would be taken by a competent urologist as a clear indication that treatment is necessary. But the PSA test is inexpensive, and would appropriately be part of the blood test that accompanies an annual checkup. Regular PSA testing would establish a baseline and permit health-care providers to track changes, which could indicate whether cancerous lesions were growing aggressively.

The news here is that an update to one of the studies used by the USPFTS has recently been published in Lancet. The study, the European Randomized Study of Screening for Prostate Cancer (ERSPC) followed 162,388 men over 13 years. A previous report on the study, published in the New England Journal of Medicine, served as part of the basis for the USPFTS’s decision not to recommend PSA screening for the general population. The USPFTS did not deny that in some cases, the PSA test led to diagnosis and treatment of prostate cancer, resulting in saving some men’s lives. Their objection, boiled down to essentials, is that it didn’t save enough lives to justify the costs, both in terms of the adverse effects mentioned above, and the economic costs.

The more recent news is that, as the observation period has continued, greater absolute benefit from PSA screening has emerged. Specifically, after 7 years, 41 cases of prostate cancer had to be identified to save one life. After 13 years, 27 cases had to be identified to save one life.

In my previous Doc Gumshoe piece, I pointed out to a huge defect in this study, and I’ll repeat it now: it was supposed to compare two cohorts – one that had PSA tests and one that did not have PSA tests. But almost half of the men in the group that wasn’t supposed to have PSA tests went ahead and had the tests anyway, which presumably also lowered the mortality in the control group and reduced the difference between the two groups.

I think the USPSTF picked the European study because it was the study that most closely supported their view. Most other studies at that point had strongly endorsed PSA testing. For example, a study from the Duke University Prostate Center underscored the very strong association between a man’s initial PSA score and his risk of death from prostate cancer. If a man’s first PSA score is between 4.0 and 9.9, his risk of death from prostate cancer is three times higher than the risk in a man whose first PSA score was less than 2.5. And if the first PSA score was 10.0 or higher, the risk of death is eleven times higher. This study points to the desirability of starting to track the PSA score earlier in life, so that men with rapidly rising PSA scores can be identified. One fundamental anti-PSA-testing argument is that it is difficult to distinguish aggressive from indolent prostate cancer, but the association between the first PSA score and prostate cancer death strongly suggests that rapid increases in the PSA point to aggressive cancers.

… and a bit more about prostate cancer…

A ten-year study, done at the Dana-Farber Cancer Institute in Boston, found that a relatively cheap drug significantly improves survival in men whose prostate cancer has already metastasized to bone and distant organs at the time of diagnosis. The drug, docetaxel (Taxomere), extended the lives of these men by about 14 months, which is considered an excellent result in clinical trials in patients with metastatic cancers. Of the 240,000 new prostate cancer cases diagnosed each year in the US, about 30,000 cases are metastatic, meaning that the cancers were detected too late. And that’s yet another reason to do PSA testing – catch the cancers before they become metastatic.

Another way the Mediterranean diet is good for us

This is another analysis based on the Nurses’ Health Study, carried out by Brigham and Women’s Hospital and the Harvard Medical School. It reports that adherence to the Mediterranean diet (fruits, vegetables, nuts, legumes, unrefined grains, olive oil, fish, and, yes!, wine) helps preserve telomeres. These are repetitive DNA sequences at the ends of chromosomes whose function seems to be to protect the chromosomes as cells divide; in themselves they don’t code for anything, they’re just little protective bumpers. Telomeres naturally get shorter as people age, contributing to chromosome damage. So, protecting telomeres is thought to be an excellent means of slowing the aging process.

The study, very carefully carried out and published in the British Medical Journal this December, followed 4,676 women in the Nurses’ Health Study and assessed their adherence to the Mediterranean diet on a 9 point scale. Each increase of 1 point on this scale corresponded to about 1.5 fewer years of telomere aging. A 3 point score on the Mediterranean diet adherence scale corresponded to about 4.5 fewer years of telomere aging, which is similar to the difference between smokers and non smokers, and between inactive and active women (that is, smokers and inactive women had about 4.5 years more telomere aging). The largest single cohort in the study, 1201 women, had a score of greater than 6, equivalent to about 9 fewer years of telomere aging.

Whether this works out to be 9 additional additional years of life has yet to be determined, but it’s clearly a good sign!

And, by the way, the only significant correlation was between the Mediterranean diet overall and telomere length. Individual components of the diet did not yield significant correlations.

* * * * * * *

Well, the Mediterranean diet certainly does not leave us with the feeling that we’ve taken in a pound of butter and quart of cream, but I’m willing to go with it, at least some of the time, as long as I get an occasional outing (once a year?) to that Indian spot at Broadway and 98th street.

I had meant to spend a little time on cancer and also Alzheimer’s disease (AD), just to update you on the news. I’ll just say that the cancer news is, on the whole, quite good. There are several quite promising treatment approaches that have yielded definitely positive results so far. One of them that I find highly promising is using oncolytic viruses to attack and kill cancer cells. Some are out there already, and more are just about to come out from behind the curtain.

The Alzheimer’s news is not nearly so good. The overwhelming majority of AD trials – 99.5% is the figure I’ve seen – fail to meet their endpoints. However, the research continues unabated, and one of the most promising avenues (I think) is looking for markers that let us identify AD early, before cognitive deficits take hold. We should be seeing some interim results from that study in the blighted family in Colombia before long, and that will surely tell us something. As always, I am guardedly optimistic.

I’ll do blogs on the current state of both cancer and AD treatment early in this New Year.

Speaking of which, Happy New Year to all! Michael Jorrin (aka Doc Gumshoe)


23
Share your thoughts...

avatar
16 Comment threads
7 Thread replies
0 Followers
 
Most reacted comment
Hottest comment thread
16 Comment authors
Rusty BrownMichael Jorrin, HowardELISSA JUNGF Riepen Recent comment authors

This site uses Akismet to reduce spam. Learn how your comment data is processed.

ScorpioRising
Member
👍1019
ScorpioRising

Excellent article Michael! Long CTIX!

DrKSSMDPhD
Member
👍47654

Agree Scorpio! Sounds like brilacidin has a brilliant future in India!

Add a Topic
247
ilovesgm
Member
👍4
ilovesgm

I am a prostate cancer survivor about 5 years in now. I am a firm beliver in the PSA test because I had a high gleason # (measure of aggressive level). I chose to go to a clinic in Alanta Georgia as an alternate to surgery. I had implanted seeds and then a few weeks later 35 external beam radiation treatments. So far I have had zero side effects. As a retired engineer along with the no surgery what appealed to me was before the treatments they gave me a 10 year survival rate of 89% from their current data… Read more »

Add a Topic
4454
Add a Topic
3397
Add a Topic
6225
mary
Member
👍789
mary

Thanks for the great, informative article, Doc Gumshoe. I’ve been wanting to try the Mediterranean diet (actually on my New years resolution list which has been the same for the last 45 years–to get in shape) but never have. The only fish I like is fried cat fish and fish sticks–do you think those would be acceptable for the fish portion of the diet?

Add a Topic
5198
Add a Topic
5198
Lulu
Member
👍1289

Thanks for the chuckle Mary!

DrKSSMDPhD
Member
👍47654

McDonald’s Filet-o’-Fish definitely counts Mary!

Add a Topic
309
astrid
Member
👍3
astrid

It is my understanding that the very low cholesterol levels recommended in America lead to a higher overall mortality despite the lower mortality by heart and stroke

Add a Topic
3820
Carbon Bigfoot
Guest
Carbon Bigfoot

I went through a myriad of medications including statins before I insisted my Doctor prescribe Lipitor, originally 40mg/daily, now 10mg. I thank Warner Lambert for the drug which lowered my combined cholesterol from the high of 280 to under 100 at the low. Due to other medical issues with their prescribed drug my last blood work-up TCol. was 180. I am also taking a generic which in my view is not as effective as Lipitor.

Add a Topic
3818
Add a Topic
5287
Add a Topic
3820
JohnM
Irregular
👍1932

If you are taking Lipitor, you must supplement with CoQ10 to avoid muscle wasting and weakness.

Add a Topic
5287
Rusty Brown
Guest
Rusty Brown

That’s a very good point. I took statins for years and the Dr. never mentioned this important point even once. I found out only after doing my own research years later.

Add a Topic
3818
Just_Checking
Guest
Just_Checking

The livestock industry in the USA is aiding the rise of resistant pathogens by feeding antibiotics to animals and fowl to increase weight gain and profits. These low dose antibiotics permit the pathogens to mutate and become resistant. Finally, the USA citizens end up eating the meat with residual antibiotics remaining.

Add a Topic
4517
Add a Topic
4517
Add a Topic
4517
Sam Simonovich
Guest
Sam Simonovich

Thank you for your very informative article. As a PSA surgery survivor I can appreciate what your article means and I feel that you are talking to me personally through your article. Thank You!

Add a Topic
6225
Rusty Brown
Guest
Rusty Brown

As I understand it, the antibiotics kill off 99.9%+ of the bacteria, leaving behind only a few individuals that happen to be resistant to the antibiotic – perhaps because their DNA experienced mutation somewhere along the way – and these few survivors go on to repopulate the host organism with generations of similarly-resistant bacteria.

Add a Topic
4517
Michael Jorrin,
Guest
Michael Jorrin (aka Doc Gumshoe)

Strongly agree that antibiotics to make infant chickens gain weight rapidly & get to the supermarket triplequick is bad for all of us, not only those of us who eat those chickens. And, by the way, my brave wife & I tried to have dinner at Awadh ( the Indian place on B’Way at 98th St) last week, and were told there would be a two-hour wait! This was on a weeknight. Lots of people wanting their pound of butter and quart of cream. So, back to the Mediterranean diet. Best to all!

Add a Topic
4517
Add a Topic
5198
Lulu
Member
👍1289

Long butter, Vit K2 and Dr KSS

Add a Topic
3932
C. E. Colson
Guest
C. E. Colson

Dear Doc — As a long-time fan, I am puzzled by how you seem to have suspended your normally-healthy scientific skepticism in your reporting on the IMPROVE-IT study. First, you failed to mention that this was not an “unbiased” scientific study, but was funded and conducted by researchers compensated by the drug’s manufacturer. Not unusual, but still, you probably should have reported that. Second, you failed to point out that the IMPROVE-IT results were revealed to the public in a very “un-standard” way: instead of being reported through publication in an expert-reviewed professional journal, they were revealed in the form… Read more »

Add a Topic
5554
C. E. Colson
Guest
C. E. Colson

ERRATUM: In the discussion of overall results/reduction in overall event rates, it should read: “– a reduction of ONLY 2 percentage points, or 2 events per 100 participants over a seven-year span” .

Thank you,

Michael Jorrin,
Guest
Michael Jorrin (aka Doc Gumshoe)

To C. E. Colson, many thanks for your careful & thoughtful comment. But I don’t think I was “uncritically promulgating” IMPROVE-IT. The study results were announced, as is quite standard, at the AHA annual meeting prior to publication in a peer-reviewed journal, and, yes indeed, as with most clinical trials, it was sponsored by the pharmaceutical company. What I think was significant, and important about the study was that it demonstrated small but significant benefit in a cohort of high-risk patients whose lipids were already reasonably well-controlled at baseline. And even though the simvastatin only group attained target LDL-cholesterol levels,… Read more »

Add a Topic
3820
Add a Topic
3820
C. E. Colson
Guest
C. E. Colson

Dear Doc G. — Thank you for your thoughtful reply. And, indeed, you did conclude your original discussion with the caveat, “This suggests (but does not prove!) …”. The lower LDL numbers of the group with Zetia do not prove that the lower LDL was responsible for the microscopically better results for that group. We have seen other clinical studies (such as JUPITER) in which lower LDL did not show reduced arterial plaque formation (a special group, I know; nonetheless, the results went the wrong way). In the opinion of many whom I’ve read, the increased cost and potential side… Read more »

F Riepen
Guest
F Riepen

I read study results and comments critically to try to discern proof, if any, that lowering LDL/Total C results in lessened cardiovascular risk. While I appreciate this good analysis, it seems your conclusion as stated is intellectually an assumption, at best. You suggest (while you appropriately also suggest it “does not prove”) – and again limiting this to high risk people – that “a reduction in LDL-C of about 15 mg/dL from an already quite low level resulted in real and significant clinical benefit in terms of lowering the rate of acute coronary events.” Perhaps all this suggests is that… Read more »

Add a Topic
3820
Add a Topic
3818
ELISSA JUNG
Guest
ELISSA JUNG

IF ANY BODY READS THE REACTIONS TO STATINS THEY WILL RUN IN THE OPPOSITE DIRECTIONS FAST. THIS BS ABOUT FATS, SALT AND SUGARS IS ALL ABOUT SELLING PILLS.
I’LL BUY THE STOCK BUT NOT THE PRODUCTS. THE BODY NEEDS, IN MODERATION THESE
ITEMS. IF YOU FILTER YOUR WATER, BUY ANTIBIOTIC FREE MEAT AND POULTRY, WASH YOUR FRESH VEGGIES AND FRUIT IN A SOLUTION OF VINEGAR AND WATER, EAT A BALANCE DIET, NOT THE ONE TOUTED TODAY YOU WILL DO FAR BETTER. I CAN PROVE IT! I’M 82, NO ISSUES, NO PILLS JUST VITAMINS AND STILL KICKING BUTT! THANK YOU.

Add a Topic
3818
Add a Topic
5971
Add a Topic
540
Howard
Guest
Howard

Elisa, We can hear you without shouting at us (ALL CAPS IS SHOUTING). Thanks.

Michael Jorrin,
Guest
Michael Jorrin (aka Doc Gumshoe)

A small reply to the comment above: the small improvement in the patients on the combined ezetimibe-simvastatin regimen was not due simply to the combination of two drugs, but to the combination of two entirely different mechanisms. Ezetimibe can in no way reduce the synthesis of cholesterol (which is how more than 80% of our body’s cholesterol is created), and the statin can in no way reduce the absorption of dietary cholesterol. Combining the two mechanisms is what made the difference, admittedly small. But it proves that addressing dietary cholesterol makes a difference.

Add a Topic
3820
Add a Topic
3820
Add a Topic
3820