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It's disconcerting when medical authorities get into a pissing match over potentially life-and-death issues — as they have, very publicly, in the last few days over new guidelines for prescribing cholesterol-lowering statin drugs.
The new guidelines could result in millions more people taking statins. Some see statins as such wonder drugs that they recommend just putting them into the public water supply, or doling them out to just about everyone over 50, but statins can also have very real side effects. The ping-ponging medical opinions in the new recommendations and resulting backlash are likely to leave many confused — me included. So I turned to an authoritative source: Dr. Vikas Saini, president of the Lown Institute, a cardiovascular specialist and a reasoned opponent of over-treatment. Our conversation, lightly edited:
So what are we, the public, to make of this great big loud debate over statins and the new risk calculator?
Firstly, for those with coronary disease or other vascular disease, statins are an essential medication in a program of prevention. Nothing has changed here.
Also, the controversial new risk calculator applies to people who don't have heart disease and are not at immediate high risk — millions of people — so there is no rush to change our practice today until we are clear on this issue of the right calculator.
To start, I'd like to quote Dr. David Newman of the Mt. Sinai School of Medicine, who has done some calculations: “We need to tell patients the actual numbers. For patients without diabetes or a prior heart attack or stroke who are treated with statins for five years, 98% will see no benefit; 1.6% will be spared a heart attack and 0.4% a stroke — and, importantly, there will be no difference in overall mortality. At the same time, 2% of individuals treated with statins will develop diabetes and 10% will have muscle damage."
Those numbers, he says, are aggregate numbers from large studies, and, most importantly, assume that "duration of therapy is 5 years, age is about 60, and comorbidities and baseline risks are relatively high." For lower-risk patients the numbers will be even more unfavorable for statin use.
Aside from risk calculations, what is new in the new guidelines is the general idea that we should treat overall risk, and not target a hard number of the LDL (bad) cholesterol. This is generally a good idea.
Even here, however, there are some problems with the guidelines, in my opinion — particularly for women.
The guidelines basically have four risk groups. There's very little debate around two of them: people with cardiovascular disease and people with diabetes. Another group is if your LDL (bad) cholesterol is greater than 190 — and if you look at the way it’s laid out, if your LDL is higher than 190, you should be on a statin.
The issue here is that if that's the only number that's wrong with you, and you're a woman and your HDL (good) cholesterol is 80 or 90 — very high and probably protective — these guidelines seem to say you should go on a statin, and yet the evidence that your group would benefit from a statin is practically non-existent.
I've had patients like this — women who have a cholesterol of 280 or 300 and they're 90 years old. And you look under the hood and their LDL is high but their HDL is also really high. There's a whole lot we don't know, and the 'cholesterol causes heart disease' meme has kind of crowded out everything else that’s going on.
On the other hand, in support of the new guidelines: There are people who have LDL (bad) cholesterol of 180 and go on a statin and it gets reduced to 120, so they’ve had a huge reduction in their risk, but the LDL is still 120. In the old guidelines, you could end up torturing the patient by going to higher and higher doses and going from drug to drug, trying to squeeze that down to 100 or less.
What the new guidelines are saying is you don’t really need to do that because you’ve gotten a huge reduction in risk, and so this is where I line up with the mainstream, which is that the underlying mechanism of how statins work appears to be more than just the lowering of cholesterol. That may be a big part of it. But they also seem to have an anti-inflammatory effect that seems to calm down the blood vessels.
So it does appear that you get a benefit from the statin even if your bad cholesterol number doesn’t reach some hard target of 100 or 70. That's part of what's driven this revision — the recognition that 'Let's be reasonable here. We're getting a big benefit. You don’t have to torture the patient to get the right number.' So that’s a big plus.
It's the last group — the group for "primary prevention" — that most of the debate is around.
These are the lower-risk patients?
Right, those are the people without known heart disease but who are at risk for heart disease. The problem there is a central problem of modern medicine. To explain, I'll make up some easy-to-understand numbers:
If you take 100 patients who had a heart attack without a statin, maybe 50 of them might have another heart attack; and with a statin, let’s say you reduce that by half, so with a statin only 25 would have another heart attack.
If you take 100 healthier people without heart disease, let's say that, in the future, eight of them may go on to have a heart attack. So if you gave 100 of those people a statin, those eight might be cut to four. Also a 50 percent reduction.
So in the high-risk group, you've given 100 people a statin and prevented 25 heart attacks; in the low-risk group you've given 100 people a statin and prevented four heart attacks.
And let’s say the percentage of people who get side effects from a statin is a steady 10 percent. If you give statins to 100 patients who've had heart attacks, you've saved 25 from heart attacks and given 10 of them side effects. Now take the low-risk group: You give 100 people statins. You save four heart attacks and you give 10 people side effects. And that’s the worry.
Now, in reality, the risk of heart attacks and the risk of side effects are both lower than my numbers — they are going to be more like Dr Newman’s numbers — so when you multiply by millions of people, you will see a lot of harms. And remember that many of the heart attacks prevented by statins are not going to be fatal heart attacks. So there is a real chance that the overall health would not improve, while you've spent millions of dollars for drugs. That's what's going on here.
And the answer starts getting even muddier because the evidence for statins working in that low-risk group is nowhere near as clear as the numbers I gave you. One example: A group in Australia calculated that if you applied the new criteria, you would be spending around $500,000 a year to save one year of life; and while we don't like to talk about this, our society has tended to define cost-effectiveness — and this is reflected in the medical literature — as being about $50,000 for one year of life saved. Now, of course we cannot put a dollar value on such things, but on that type of scale, statins for low-risk patients is 10 times less cost-effective.
But how about from the point of view of an individual patient? I can imagine people saying, 'Okay, I’m pretty low risk, so my chances of getting side effects are higher than my chances of being saved from a heart attack, but I’m really scared of a heart attack and I’m not scared of side effects, so why not err in that direction?'
When you talk about the individual patient, it’s reasonable to have that conversation. In fact, when you read the guidelines, they themselves back off a bit at the end to say, 'At the end of the day, a doctor and a low-risk patient should talk it over.' So I think that's fair.
I can tell you that there are patients whose lives have been ruined by side effects of statins.
Permanently ruined. It’s not well known, and it’s not very frequent, but it happens enough that the idea that these are just harmless and put them in the water is just plain wrong. We don’t know what the long-term impact of the increased rate of diabetes from statins will be. And the more common effects like muscle pain might seem like ‘nuisance effects’ to some doctors – (“After all we’re saving lives here!”), but they’re not ‘nuisances’ to those who have them, especially if they take months to go away. One of the worst things about our system is that we seem to figure out all the side effects by experimenting on the whole population for a few years
So statins are not a panacea. And yes, in a low-risk group you should talk to your doctor. But here’s the other part of the puzzle — and this is more of an editorial than about the statin issue: We live in a society and a system where the answer to these problems is the pill. Well, let me ask: when was there a head-to-head comparison of an intensive program of diet and exercise against statins? Never. There was such a trial for diabetes, and guess what? Lifestyle won.
A recent trial of the Mediterranean diet for primary prevention reduced events significantly, approaching the reduction from statins — and many of those patients were taking statins already! So I think a head-to-head comparison of diet against statins would be very interesting.
So when we’re talking about the low-risk group, the group of millions of people who are going to be put on statins, it’s irresponsible to talk about drugs without emphasizing all the other things we need to do to be heart healthy. Many of the people who say you just need to go on a statin will say, 'I tried talking to my patient and they tried a diet and it's just too hard and it just doesn’t work.' That's often true but it's also true about smoking, yet at the end of the day we've had a huge impact on smoking, we've changed the norm of what's acceptable and we've changed the laws, and we've changed behavior.
So yes, at the individual level, if a patient is fully informed of the pros and cons and sees and understands the numbers, I would say I'm okay with them going on statins. And in general, the higher the risk, the more likely you are to benefit from using a statin, and that aspect of the guidelines is correct. However, the most important point is that the threshold at which you flip into using statins, that tripwire point of risk — is it 5% or 10% or 7.5%? — that's going to vary from person to person, and is really a personal preference on risk and tolerance. It's about each individual's understanding and reaction, and there's no One Size Fits All. If Dr Newman is right – and I think he is — my reading of the data tells me that the proper risk threshold, is higher than 7.5%. It certainly would be for me. Otherwise, you’ll take more drugs, but not see better overall health.
Amid the debate, there have been some insinuations about financial conflicts of interest possibly having distorted the guidelines. Do you suspect that?
The guideline writers seem to have taken at face value some studies that take some leaps of faith. And the fact that smart people take these leaps of faith without recognizing them as such -- that's where the concerns about conflicts of interest arise. Because when there is a chain of money and friendship and group thinking and group etiquette that drives the process — perhaps without thinking — that creates blind spots. Financial conflicts of interest aren't so much about venality (though sometimes they are that). They're about the blind spots of well-meaning people. And the lack of open source access to some of the critical drug company data that drove these recommendations removes an important potential disinfectant.
But here’s the situation from my point of view. For those without heart disease (“primary prevention”) who don’t have a high risk from the other risk factors besides cholesterol, the data for using statins is not as strong as people think.
For instance, there was a paper published in Lancet which is one of the supports for the new guidelines. The paper concluded that statins are net beneficial for primary prevention because they did a computer model which found benefit for patients without vascular disease and at moderate risk.
However, when you look under the hood at their results (buried in the appendices) they don't add up. Why? because they found no such benefit in the same moderate risk groups with vascular disease — a group which by definition is, and has always been, considered at higher risk — they have vascular disease already — and yet statins didn't benefit them! That seems weird. Out of 4 subgroups like this they found a benefit in only 1 — the one they used to draw their conclusions from, and made the headlines with and started the bandwagon for using statins for primary prevention.
As far as I can tell, it seems that this paper and its models seem to be the major source of the otherwise mysterious pick of the 7.5% threshold. There is no direct derivation of this number in the new guidelines document — just a reference to "clinical trials show that...." And in the end, it looks to me like the right risk threshold for statins is higher than 7.5% for most people, even if you eventually got the calculator correct.
Readers, lingering questions about the statin debate?
This program aired on November 20, 2013. The audio for this program is not available.
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