A Heart to Heart Talk: The Statin Intolerance Controversy at ENDO 2018

Tannock 2013

As ENDO 2018 in Chicago quickly approaches, we thought a preview of a heart-specific session would be ideal for this month’s issue, especially since it coincides with American Heart Month and Valentine’s Day. The University of Kentucky’s Lisa Tannock, MD, gives us the details about her Meet the Professor session on statin intolerance and explains why the topic inspires so much passion on both sides.

February’s focus is on cardiovascular endocrinology, but it’s also the month before ENDO 2018 in Chicago. Lisa Tannock, MD, an endocrinologist and lipidologist at the University of Kentucky in Lexington, will be presenting a Meet the Professor session on statin intolerance, which is sure to lead to some lively discussion, given that the topic is so controversial.

Endocrine News caught up with Tannock to talk about what makes statin intolerance so controversial and get a preview what she plans to present.

Endocrine News: Your Meet the Professor session is on statin intolerance. What should readers know about that?

Lisa Tannock: I guess the biggest thing to know about statin intolerance is that it’s very controversial, and it triggers a lot of emotion on both sides. When I speak on this, for example, there’s always a few people in the audience who have complete opposite beliefs than I do. Part of the controversy right now is that a new class of drugs called the PCSK9 Inhibitors are now available. They’re not indicated for statin intolerance, but prior to their existence, there weren’t really good alternatives to patients or providers who thought their patients were statin intolerant. Now these are available, they don’t have that indication so it sort of increased the controversy, if you will.

EN: Why is statin intolerance controversial in the first place? If these patients can’t tolerate statins, then they need to be treated some other way, correct?

LT: That’s the question. Part of the controversy is, what is statin intolerance? The vast majority of the time when we are talking about statin intolerance, we are talking about muscle aches and pains, and there’s a number of really good clinical studies that have not found any statistically significant difference in muscle aches and pains between statin users and the people assigned to placebo. And so that’s the side that I come down on. In my opinion the clinical trial evidence doesn’t show a difference between statin and placebo, and when I get cynical I say, “It’s 2018, who doesn’t have muscle aches and pains?”

But that’s very controversial, and so for people who do have muscle aches and pains, I’m not saying they’re not real; I’m just saying that the preponderance of evidence suggests that they’re not attributable to statins. I think that’s what’s very controversial. There’s a lot of research, clinical studies, there’s been some muscle biopsy type studies, trying to find the pathology of it, and there’s an extreme condition called rhabdomyolysis that is real. That’s not what we’re talking about here. We’re talking about muscle aches and pains, usually with no biochemical abnormalities. I’m never saying the pain is not real; it’s whether it’s truly due to statins or not.

For example, there are studies where they take people who report muscle aches and pains to two or more statins, typically. Then they randomize them, blinded to either statin or placebo and about two thirds of the patients have muscle aches and pains, regardless, and only about one third, if that, have aches and pains only on the statin and not on the placebo. And so maybe there’s a very small subset that do have statin-specific muscle aches and pains, but the vast majority of patients who have muscle aches and pains on statins have it also on placebo in these studies.

There’s a handful of people, often doctors, who themselves had muscle aches and pains on statins, and used their personal experience. They will challenge me, and I’m not sure I look forward to that challenge, but I expect it and I don’t walk away from it. I’m happy to discuss it.

EN: Do you have patients who refuse to take statins?

LT: That’s one of the big issues. A lot of times, patients say, “Oh, I can’t take statins, because I have muscle aches and pains,” and yet if we could do a blinded placebo controlled study on an individual patient, they might have the same aches and pains to anything we gave them, regardless. That’s a challenge and there’s a group of providers out there that adamantly believe in this, and they will tell a patient that they’re statin intolerant, that they should never, ever take a statin. And in my opinion, the only person who should be told that is someone who has had rhabdomyolysis. It’s a challenge for how to manage the cardiovascular risk of these patients, given that statins are so clearly beneficial in so many ways, and up into recently it was a choice only between a statin or really and truly second best, the other lipid-lowering agents we had, which are all a little inferior to statins in terms of the cardiovascular outcomes data that we have.

But with the PCSK9 Inhibitors, these guys are more potent than statins in terms of LDL lowering, and although the studies have only been done in really high-risk patients at this time, they also lower cardiovascular outcomes, so the PCSK9 Inhibitors are a great class of drugs. Incredibly expensive, but there’s also a potential market for them for the companies that make them, to recoup some of the [research and development] dollars if they can get the indication for statin intolerance, then that hugely expands their current indications and would hugely expand their market.

EN: Sounds like patients are doing some research themselves.

LT: I don’t understand the link, but there’s the mind over medicine concept, right? If a patient believes they’re in pain, they’re in pain. If a patient believes they’re not in pain, they’re not in pain. There’s no way for us to quantify or measure that or test it.

EN: Is there research on the other side? If the patients stopped taking statins, do their aches and pains magically go away but their cardiovascular outcomes get worse?

LT: Yes. If you have a patient with aches and pains on statins and you take their statins away, their aches and pains get better because they’re believing it’s better. We know that cardiovascular disease is higher in non-statin users than it is in statin users.

EN: Tell me about your presentation that you’re working on for ENDO 2018.

LT: Meet the Professor is usually a case-based discussion, and I’ve done Meet the Professors on a number of different topics, all lipid related, and usually I try to go through two or three cases, just to share the experience and the alternative plan and what you’re able to do with a patient. If a patient refuses to take a statin, what are the alternatives? PCSK9 Inhibitors are one, but then we’ve got the good old standbys. We’ve got bile acid resins, niacin, fibrates, and ezetimibe. I talk about the different options that we can do. But part of what I typically try to talk about is some of the success that I personally have had with patients, leading a patient to recognize that they have muscle aches and pains that are independent of the statin use. I had this one patient, years and years ago, who kept a really detailed symptom diary, and what she eventually realized is she still had aches and pains even when she wasn’t on the statin, and of course she knew if she was on the statin or not.

When she wasn’t on the statin, her symptoms were pretty much the same. It’s just that when she was on the statin, she had a target to aim her frustration at. I used that as an example. That was a particularly successful patient who eventually came around to understand that she had muscle aches and pains, no matter what. We never did find a diagnosis and she eventually came around to believe that her cardiovascular risk would be lowered by use of a statin, and chose to go on it, and really per her symptom diary, she continued to have muscle aches and pains but it wasn’t worse. And so I try to do that with a lot of my patients and that’s an example I usually talk about.

EN: You talked about leading a patient to realize statins are beneficial.

LT: If I have someone who was referred to me with statin intolerance, which is typically the way they get in to see me, my preferred approach is to review which statins they have tried and to try at least one or two more, and to work with the symptom diary when they are on statin, off statin, to try to see if there’s a difference. Like I said, one patient in particular said, “I have the same symptoms regardless.” Leading someone to self-recognition is a great step. But a lot of times, when I do that, patients say they have symptoms only on that statin, and not when they’re not on the statin, and of course I can’t do a blinded placebo trial, so they’re reporting on their recollections and impressions.

Then I talk about the next approaches, and look at the cardiovascular risk and using the risk calculators — a lot of times these patients have already had a heart attack — that’s usually who’s sent to me and we talk about all of the other things we can do to try and reduce that risk: blood pressure, aspirin, and quitting smoking, and all those things. Then we talk about the different ways to treat their lipids. I work in Kentucky, and my patient practice is very heavy Medicaid and Medicare, and so I don’t have a lot of access to PCSK9 Inhibitor drugs, because it’s not what they’re indicated for. I mean I think in my practice I have maybe three or four patients on those right now, so that’s not an option for me. A provider who works in a major metropolitan area with a lot of their patients having private insurance may have a lot more access to those drugs. They’re great drugs. As far as we know, they’re great drugs, and I’m not bashing them, I just don’t think they need to be used in many cases.

EN: Since this topic is so controversial, I’m sure you’re expecting some people to stand up and refute you or ask questions, so what would you say you want to get out ahead of that?

LT: Basically, it’s a challenge every time I give a talk on this topic. There’s a handful of people, often doctors, who themselves had muscle aches and pains on statins, and used their personal experience. They will challenge me, and I’m not sure I look forward to that challenge, but I expect it and I don’t walk away from it. I’m happy to discuss it. I just try to talk about my knowledge of the literature. And you know an anecdotal experience, especially if it’s yourself, is a very different experience than what the literature reports on, tens of thousands of patients at this point in all the statin studies.

I gave a talk on this topic at my own institution a year or two ago and one of my colleagues —  another internal medicine sub specialist — said that he himself had had debilitating muscle aches and pains on a statin, and what was interesting was that he disclosed that he truly believed it was statin-related, but he also believed the benefits of statins outweighed the risks, and so he had tried every single statin out there and finally found one that he found at least tolerable. And I said, “That’s a good point, this is someone who knows — he’s a physician, he knows the literature and he knows the benefit and he chose to live with his muscle aches and pains because he thought the benefits outweigh the harm that he was experiencing.” So sometimes, we get there.

  • Bagley is the senior editor of Endocrine News. He wrote about the controversies surrounding imaging of pediatric patients to diagnose congenital hypothyroidism in the January issue.