2.20.2008

The Cholesterol Controversy, or Are We Getting Fleeced by Statins?

5 billion a year, according to this wellness site that I found with a Google search, is how much the big drug companies are fleecing the public for. A lot of this flap came from the 'failed' Vytorin study, which is unpublished but findable in the Medical Letter here, and in a statement from the American College of Cardiology here.

The study was a randomized trial of people with Familial Hypercholesterolemia and showed no difference--actually, Vytorin was less effective than simvastatin--in slowing the growth of plaque. Forbes said their stock tanked. The wellness site above points to it as evidence that lowering cholesterol is a farce (and, of course, we should buy his book).

The Health Beat blog, which I like but which appears to have a bias against pharma, takes on the topic here. For a bit, I felt betrayed. Here I had been talking to people about lowering their LDL and treating cholesterol for weeks, and the dogma is that statins as a class are being used more and more, not less.

We've been looking at pictures like those at right for years of medical school, learning how to treat it with drugs. Don't they work? Well, actually, yes. Let's talk about endpoints. There is a big study in the Lancet in 2008 (PubMed ID 18191683 at pubmed.gov) that was a meta-analysis of 18,686 diabetics which supported a reduction of 1/3 in major vascular events.

A 2006 study in the Archives of Internal Medicine (PubMed ID 17130382) showed a reduction in major vascular events with NO reduction in all-cause mortality. There was, of note, a 14% reduction in the incidence of stroke.

Critics, including Health Beat, argue that lowering LDL numbers do not affect all-cause mortality and therefore are not useful as there is no quantifiable evidence that quality of life goes up, and there are side effects to statins. True. Also, the Lancet article in particular is a meta-analysis of industry-funded studies, which it admits.

Still, large meta-analyses are about as trustworthy as evidence-based medicine gets, and many drug studies are industry funded.

Are statins a fraud? Just money? A plot by Big Pharma to fleece us of billions?

Of course Big Pharma wants to make money, and tons of it. It is the fundamental mission of private companies to make lots of money and they should. No one should have any illusions about that. This perhaps goes towards why we should have a public health care system. But I digress. The question is if people were fleeced, should ask for their money back, were betrayed, and so on. The wellness sites and others point out that lowering cholesterol naturally with diet and exercise is a better way to do it and statins are a rip-off.

Guess what? We tell our patients that. We say, you should lose weight, eat right, and exercise. A lot. Now. And how many do? In six weeks of primary care, I saw TWO people who had done that. They were healthy, happy, had great numbers and a very high quality of life. We encouraged them, held them up as examples. TWO of them.

So should we avoid treating with statins? If I have a person who, for whatever reason (perhaps because they're a tad lazy) can't lose weight, watch their saturated fat intake, or exercise, should I tell them to just go away? Umm...no. Should I avoid giving an elderly, male, smoking, diabetic a drug that might reduce his chances of having a stroke because he SHOULD quit, eat greens, and run a marathon? No. I'll tell him that every visit. But guess what? He just might not listen.

We should accurately represent what statins do: they make a noticeable difference in the risk of a cardiovascular event, but it is mild. It's not a miracle cure. You should stop if you get muscle aches and so on.

But call them a con and a fleece? Western medicine has said all along that patients should eat right, exercise a lot, not smoke, lower their stress level, and so on. It's easy to jump on the statin 'push' and say doctors and the medical establishment are just in it for the cash, because it absolves all those sedentary junk-food eating patients of any responsibility for their terrible disease burden. As an added side bonus, it often helps sell diet books and alternative medicine, which as far as I know, doesn't come with a money-back guarantee, either. Far from it.

OF COURSE Big Pharma wants to make money. Most doctors (I admit, not all) want to help patients. And we figure that even those people who choose not to modify their lifestyle deserve some recourse to try and prevent badness. Crazy us.

To close the circle, let's go back to the Vytorin study. The drug failed to beat simvastatin with regards to thickness of plaque in people with FH, a rare genetic disorder. So, the endpoint doesn't matter (mortality, heart attacks, and strokes matter) and the population is not applicable to every patient. Is it disappointing? Sure. Does it mean statins don't do anything? No. Patients and doctors shouldn't rely on them to get them out of the work of modifying behavior.

There is no quick fix.

6 comments:

Anonymous said...

The NNT for primary prevention is much too high given the risks. I was diagnosed with Parkinson's disease which I feel was triggered by or unmasked by the use of Lipitor 10 mgm/day for 4 yrs. If you review the metabolic substrates of the mevalonate pathway that are blocked by HMG CoA reductase inhibitors, the plausibility of statins having causality in the development of neurodegenerative diseases is evident. Perhaps taking out your Biochem text and reviewing both this pathway as well as the known functions of cholesterol will change your outlook....

A, a fourth-year medical student said...

I'll take a look, I admit I have forgotten the points you mention. I should say that in general I think anyone who has symptoms should stop a medication, but it sounds like in your case it wasn't so easy? Are you still struggling with Parkinson's?

Anonymous said...

The Parkinson's symptoms appear permanent. one of the products of the mavelonate pathway is coenzyme Q10--serum, muscle and platelet levels of coq10 are depleted by statins. This same substance, coq10, is being utilized in Phase III trials for PD, ALS and Alzheimer's in megadose units--1200mgm for PD, 2400mgm for Alz and 3000 mgm for ALS. Deficiencies of coenzyme q10 have been proven in neurodegenerative diseses, thought to be part of the disease process itself. Does it not seem counterintuitive to give a drug that depletes a substance ALREADY depleted by the disease itself? Statins deplete selenoprotein production (and thus glutathione reductase--major part of the brain's antioxidant system. Statins deplete many other substances--including brain cholesterol, dolichols, GTPases translational proteins...and more

A, a fourth-year medical student said...

I have up until now associated CoQ10 with heart disease; do you have authors for the articles above? They sound interesting.

It does seem counterintuitive; the decrease in PD mentioned in the article I posted in 'statin update' was subject to all the weaknesses of a retrospective study.

Although it's never as good to replace exogenously the product of an edogenous pathway, I wonder if CoQ10 supplementation would be worth it for those using statins...for example, those who have had heart attacks already for whom there is a proven benefit.

Very thoughtful posts, you've brought to light a lot of things I didn't know. I'm sorry you've been affected in this way.

Anonymous said...

My doctors put me on statins when I was scrambling through rough dirt trails 5 km daily, 45 gym workout daily, 25 lengths in the pool, then, a deepwater weight belt workout (from the book Water Power Workout), stretching, hot tub.

I can just walk 2 km in over 2 hours now, four years after last statin use. I may never recover the deconditioning and weakness. they keep telling me to take statins. I refuse.

Crazy me.

Anonymous said...

Here's the work that led to the Lancet article. I hope your career will culminate in your some day being this qualified, accredited and respected, and that done without taking industry money. I believe you will have heard of the Cochrane Collaboration?

http://ti.ubc.ca/