Statin Intolerance

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: Christie, some [patients] really can’t take a statin, and there was a recent statement on statin intolerance. Can you tease out for us what the current thinking is on statin intolerance? I know it’s sometimes difficult to define and identify.

Christie M. Ballantyne, MD, FACC: The [National Lipid Association] had a recent update on this. First of all, you have [patients] who can’t tolerate any dose of a statin, then you have [patients]—we’d call it maybe partial intolerance—[who] can tolerate some dose of a statin. [Therefore], you always try at least 2 statins. You always try a lower dose, and you can [try an] alternative the day before you’re going to call someone statin intolerant. If you can get them on some dose [of a statin], you’ll do that. And it’s important to screen for secondary causes [of statin intolerance]; [for example], hypothyroidism. Look at their other medications. We know there’s an important nocebo effect for this.

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: Nocebo, that’s not placebo.

Christie M. Ballantyne, MD, FACC: Placebo, nocebo.

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: That’s nocebo.

Christie M. Ballantyne, MD, FACC: You mention [that] if people know there’s harm [with] a drug, then you’re going to associate your symptoms with that [drug]; [for example], muscle soreness. Keith, if you’re someone my age [and] you go out and exercise hard…

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: You’re going to hurt.

Christie M. Ballantyne, MD, FACC: You’re going to hurt. That’s just a fact that you’re going to get some sore muscles. Well, is it the statin? Is it because I’m getting old? Or is it just [that] I worked out? The issue that comes up [is] it’s not easy to tease that out. [For] many [individuals], maybe it’s not [statin intolerance]. But as a physician, if I see a patient and they tell me [they feel bad when they take a statin]—some of our colleagues will say, “That’s just in your head.” Well, aren’t all my feelings in my head? What are you telling me, [that] I’m crazy or something? You [have] to look at this as [though] our perceptions are our reality, so I’ve got to work with them. We have tools to do this; we optimize lifestyle, we do alternative dosing, [and] we have nonstatin therapy. Rule out secondary causes but [still] treat that individual. We don’t just give up if someone says [they] can’t take a b-blocker. We used to use crazy doses, or it was Aldomet [methyldopa] or clonidine, [but] we didn’t give up on blood pressure. It’s the same thing [here]—go [to] plan B, go [to] plan C.

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: Dr Michos, [are there] any pearls you want to suggest on statin intolerance? I recognize it’s a difficult field, but what do you do?

Erin D. Michos, MD, MHS: I have the same approach as Christie. There may be a strong nocebo effect, but these symptoms are real to the patient. Certainly, we try to get them back on a statin through counseling, [then] try to reinitiate and do every-other-day doses. I’ve had good success with getting [patients] to at least take rosuvastatin 5 mg 3 times a week, but the bottom line is that medications don’t work in patients who don’t take them. If they’re not going to take them because the symptoms are very real to them, the good news—and we’re going to talk about this next—is we have multiple other nonstatin options. Statins are no longer the only game in town, although they’re still important and the first tool we start with when we go to pharmacotherapy. If you have a really high-risk patient, it’s important to get [them] to [the] goal quickly. You don’t have to waste a lot of time trying all 6 statins. You try at least 2, then you [have] to move on. It’s important just to get our patients to [the] goal and to start thinking about initiating these nonstatin therapies once you’ve demonstrated that they’re above their threshold on their maximally tolerated statin. For some patients, the maximally tolerated statin is 0 statin, so then you would follow the algorithm with moving onto the nonstatin therapies.

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: I’m going to come right back to you on the nonstatin therapy. Christie, [did] you want to say something?

Christie M. Ballantyne, MD, FACC: No; I’m just nodding in agreement.

Mary McGowan, MD, FNLA: I want to mention something. I totally agree with everything that’s said. I think…by the time a patient gets to us with statin intolerance, they’ve already interacted with their primary care provider [several] times, and sometimes there’s a degree of frustration. The 1 important thing I’d add is [that] when I see a patient, I’ll say, “We’re going to work on this. We’re going to get you to where you need to be. There are lots of tools in our toolbox.” Sort of disarming [patients] to let them know you believe them. Because for [many of] these [patients], it’s a very real thing…. It’s important that we don’t dismiss [patients] who say they cannot tolerate a statin because for whatever reason they can’t.

Christie M. Ballantyne, MD, FACC: Joint decision-making—both of you have done a lot with that.

Payal Kohli, MD, FACC: A lot of patients with the nocebo effect feel better when they take CoQ10 [coenzyme Q10], for example, even though the randomized trials have not shown benefit for CoQ10.

Christie M. Ballantyne, MD, FACC: If you feel better, you feel better.

Payal Kohli, MD, FACC: You feel better. Or vitamin D, that’s another one where there were some early observational studies that suggested vitamin D deficiency may exacerbate statin intolerance, but that didn’t pan out in the VITAL substudy looking at a randomized trial. I like to think of 3 degrees of freedom when it comes to the statin: the type of statin, the dose, and the frequency. You’re kind of fiddling around with all 3 of those. I [also] love Christie’s analogy of blood pressure, because while you’re fiddling around, you [don’t want to] leave it untreated. So, you want to use nonstatin agents to treat while you’re fiddling around, then you figure out where you end up.

Transcript Edited for Clarity