Statin Intolerance: How to manage it in clinical practice

Podcast Transcript

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Betsy Stovsky: I'm here today with Dr. Leslie Cho, who is Section Head of our Preventive Cardiology Section, and also the Director of our Women's Cardiovascular Center. And we're going to talk about a very important topic, which is statin intolerance.

Dr. Leslie Cho: Yep.

Ms. Stovsky: So how do you define statin intolerance?

Dr. Cho: So statin intolerance is defined as inability to take two or more statin at its lowest dose. And statin intolerance has been something that people have debated over for years. And people have thought, "Oh, it doesn't really exist because in trials, we didn't see it." But in the real world, it affects five to 10% of patients.

Dr. Cho: People take cholesterol-lowering medicine, and within about a month of taking it, they start getting severe muscle aches. And the muscle aches are in the big muscle groups, so in your arms, or in your shoulder, or in your thighs, or your buttocks on both sides, not just one side more than the other. And the other side effect is your liver function test being elevated.

Dr. Cho: But the number one cause of statin intolerance is muscle ache. It goes away one month after stopping it. It's commonly linked to, it's more common in the elderly, it's more common in females, and it's more common with more potent, high-intensity statins.

Dr. Cho: So, for example, it's more common in Zocor or simvastatin 80 milligrams, or an atorvastatin or Lipitor 80 milligrams. So higher the dose, the more potent the statins, more likely that you would have statin intolerance.

Ms. Stovsky: So when you have a patient that has statin intolerance or those symptoms, do you try to treat the symptoms? Do you try and change the meds that they're on? Or, change the meds? How do you approach that?

Dr. Cho: Yeah, so the number one thing we like to do, is we want to see what is causing the statin intolerance. So common things that are causing the statin intolerance are such as taking alcohol, because alcohol prevents those statins from being eliminated. So you really have to limit the amount of alcohol you take.

Dr. Cho: Also, commonly prescribed cardiac medicines like diltiazem or amiodarone can interfere with statin elimination. So you have to be careful about that. There are antibiotics that interfere with it. There are other cholesterol-lowering medicine like Tricor or fenofibrate that decreases elimination. So you have to look for causes first.

Dr. Cho: The other sort of important thing is, patients take herbal supplements, which can contain another type of statin that's quote unquote, "Herbal." That can eliminate, that can prevent statin elimination. And so you have to make sure that those are not the causes. Because if they are, it's easy. You stop it or you change other medicines around.

Dr. Cho: If they are truly intolerant, one way is for you to switch to a different type of a statin. So statins are considered either like lipophilic or hydrophilic. Hydrophilic statins are things like rosuvastatin, Crestor, or pravastatin, or Pravachol. They're less likely to go to your muscle. Everything else is lipophilic. Lipophilic are Lipitor, Zocor, fluvastatin, all those other ones, they're more likely to go to your muscles.

Dr. Cho: So we tend to put patients on the hydrophilic, rosuvastatin or pravastatin. We start once a week, and then we slowly titrate to twice a week, Monday and Thursday. And if they can tolerate that for a couple of weeks, then we go to every three week, every other day, or we increase the dose.

Dr. Cho: The important thing when you start intermittent dosing is, we think the better drug to start intermittent dosing is rosuvastatin because of the longer half-life. But you can start pravastatin. You do it once a week for two weeks, and then you go to twice a week for two weeks, and then you can increase the dose, or increase the frequency as the patients tolerate.

Dr. Cho: True statin intolerance are people who cannot take even not one statin a day is extremely rare, a week is extremely rare. It's extremely rare.

Ms. Stovsky: So you've been actually studying this for a while.

Dr. Cho: Yeah.

Ms. Stovsky: You have a program. Can you talk about the program and then the outcomes that you've seen with this approach?

Dr. Cho: Yeah, so we have the largest experience in the world of treating statin intolerant patient. We do a thorough history and physical. And if it, and it turns out that they are truly statin intolerant, we start them on once a week rosuvastatin. And then we start them at the lowest possible dose.

Dr. Cho: We start at 2.5, and then, if they're able to tolerate that, then we go to 2.5 Monday and Thursday. Then we go to five milligrams Monday and Thursday. And then as they are able to tolerate, we increase the dose.

Dr. Cho: Of the patients who are truly statin intolerant, or who are intolerant to two or more statins, 70% of them can take statins. 60% of them can take it every day, once we start this slow process. Another 10% could take it three times a week. And it's only the rare patients, the 30% who really can't take any.

Dr. Cho: If they can't take any, then there is other good solution out there. There is Zetia, which is ezetimibe. It lowers your cholesterol 15%, but then really the thing that has changed the statin intolerant treatment is the PCSK9, like Repatha, evolocumab, or PRALUENT, which is evolocumab. It's an injection. You do it every two weeks or once a month, depending on how you respond to the injections.

Ms. Stovsky: So when you're looking at the patients with statin intolerance, what are you looking at a certain goal, as far as like their actual cholesterol levels? And are they meeting those, using this program?

Dr. Cho: Yeah. I mean, we have a excellent ... So before PCSK9 came out, we would follow our statin intolerant patients. We divided them into primary versus secondary. For our primary prevention patients, our goal was less than a 100. For our patients who are secondary prevention, our LDL goal was less than 70. And we were able to meet that in majority of our patients, and when I say majority, I mean like 90% of our patients. And so we've had very, very good success.

Dr. Cho: Now it's not just medicine, obviously. It's diet, and exercise, and everything else that goes along with it. Many times, these patients who are statin intolerant have to be on statin plus Zetia, in order to get there. But with all of these things, they're able to achieve their goal.

Dr. Cho: Now there are people who have genetic cholesterol problems, or people who have very aggressive cardiovascular disease with multiple events, who are statin intolerant. And for those patients in the era of PCSK9, it makes good sense to put them on PCSK9 first.

Ms. Stovsky: So are you seeing with these new drugs, I mean, it's very exciting.

Dr. Cho: Yeah.

Ms. Stovsky: This is new. Finally, something new over the past couple of years. But are you seeing that this will make a big change?

Dr. Cho: Oh, yeah. Yeah. I mean, I think the best trial on statin intolerant patient comes to us from Dr. Nissen, here at the Cleveland Clinic, where he did this study, where he took statin intolerant patients. They had to truly be statin intolerant. And the trial is very clever, it's a double-blinded crossover study, which means, they gave you a placebo and they also gave you statins.

Dr. Cho: And if you had muscle aches on statin, you can get into the trial. And so in that study, 40% of the patients were able to get into the active study arm, and they were able to show an excellent reduction with very well-tolerated side effect profile. Patients who have lifestyle limiting muscle aches on cholesterol-lowering medicine were able to take these drugs without side effects.

Ms. Stovsky: So if you were going to leave us with kind of a summary, what would you like to tell other healthcare providers about statin intolerance?

Dr. Cho: So statin intolerance is a rare entity, but it is ... So statin intolerance is more common than was previously thought, but still rare. So it's really important to take a careful history and physical. It's really important to eliminate some of the causes that can exacerbate muscle aches on statin. If there are no causes, then to do the intermittent dosing. And if you still are not at goal, then consider PCSK9.

Ms. Stovsky: Thank you very much for joining us today. And thank you Dr. Cho.

Dr. Cho: Thank you.

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