**EP58: Consultation About Statin Intolerance**
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G'day, it's Warwick Bishop here, and today I've got the opportunity to record for a podcast and consultation with a patient who has agreed to be recorded, and his wife will be in attendance. I've got Brad, who's the patient, and his wife, Joanne, or Joan. Joan. So, we've got Brad and Joan. Thank you very much for agreeing to let me record this.
By way of background, Brad's a patient I've been looking after for a year or more. We've scanned his heart using cardiac CT imaging and demonstrated some plaque, and I've put him on lipid-lowering therapies. Now, Brad, tell me how the last couple of months have been for you.
**Brad:** The last couple of months, I've been having very, very bad, more nights than days, but the nights have been hot, painful. In my joints and my body, headaches, a lot of nasal congestion in the morning, coughing during the day particularly in the morning, and again aching joints, shoulder, right foot, left knee, fingers, hands, wrists, swelling.
**Warwick:** So with that as a background, what did you do in the last couple of months?
**Brad:** I was beside myself. I didn't know what was going wrong with me. And I thought, well, maybe it's an arthritis problem, expecting, because of my age, that it possibly could be. But because a lot of the symptoms were occurring at night and I was taking my statin, the pravastatin, just before going to bed, I thought, well, maybe the pravastatin was the cause for a lot of what was happening at night. So I stopped it to see what would happen, and I found a diminishing of it but not a complete reprieve of pain and symptoms.
**Warwick:** Over what sort of time, Brad, would you say the symptoms improved?
**Brad:** Four or five days?
**Warwick:** Four or five days, I think. Yeah, okay.
**Joan:** He was definitely saying he got up and felt much, much better.
**Warwick:** And you noticed that as well?
**Joan:** Yeah, well, he was definitely saying he felt so much better in his muscles and didn't have that muscle pain that he had.
**Warwick:** Yeah, okay. And so just for my own awareness, you were on pravastatin, a maximal dose, and ezetimibe?
**Brad:** Azatrol, whatever it's called.
**Warwick:** Azatrol. And Joan's just got an important call that she's attending. Okay, so are you still on either of those agents?
**Brad:** No, what happened was after that period of time, I still had a little bit of a symptom, but a lot of it had diminished. But I thought, I wonder if it could be the ezetimibe and not the pravastatin, or a combination of both. So I decided, okay, we'll stop the ezetimibe also.
**Brad:** I feel so much better, clearer in my mind, no more coughing, no nasal drip, no more aches and pains, or minimal, very minimal. I'm able to sleep better. I haven't got the sweating like I had at night, the swelling in my wrists and joints. I just felt so much better.
**Warwick:** So the difficulty, although not the difficulty, this... What we have to really negotiate around here is a couple of things. One is to try and be clear that it is the statins or the ezetimibe or the combination of both causing it. Now, there's been a couple of recent studies. I don't know if I touched on these when I spoke with you before, but because there's some new agents on the market which work through a different mechanism altogether to the statins, they've done some studies to see if these new agents might be good for people who are intolerant to statins.
**Warwick:** And before they started the study, what they did was they took a whole heap of patients, about 4,000, who they not only swore blind they couldn't take statins, but their doctors swore blind they couldn't take statins. That's why they enrolled them into the study. So to try and clarify exactly what their status was, to be intolerant to statins, they put them on a cholesterol-lowering agent, they put them on a statin in a double-blind, randomized, crossover way over a period of six months. Now, they did that to really try and get a feel for how intolerant these people were to the statins.
**Warwick:** So I'm going to ask you just a question, which is how many people do you reckon were taking the statins at the end of that six months without any side effects or side effects that were the equivalent of being on placebo? Remember, 100% of these people were sworn intolerant to statins, had side effects, couldn't take them. How many do you reckon at the end of that six months were taking the statins without side effects or with the same rate of side effect as a sugar tablet?
**Brad:** I'd say probably half.
**Warwick:** Take into account human nature.
**Brad:** I was going to say maybe 80%.
**Warwick:** 70%.
**Brad:** 70% of those people were taking the tablet that they swore they couldn't take. And you've just given me a very passionate description of how crook you felt on, how well you felt after. So you would be one of those.
**Warwick:** So the significance of that study is this. It means that there's a lot of people who potentially blame the wrong thing. So this is really important to understand because the statins for the right people work. So 70% of the time the statins may be being blamed wrongly. But it also means that about 30% of the time people are really getting side effects. So we've got to take both sides of that bit of information.
**Warwick:** So our issue for you is very much trying to tease out whether it's the statin. And we know that in your own past, you were on pravastatin for 10 years without a problem.
**Brad:** Exactly.
**Warwick:** So this is a really good start. So the simple thing from where I'm sitting is, oh, just, Brad, go back on that. Let's start with that.
**Brad:** Absolutely.
**Warwick:** So if we work through this in a really systematic way, we get clearer information. And the information is to try and ascertain is it really the statin because we are all getting a bit older. I went and had a bit of a surf on the weekend; if I was on a statin, I would have woken up this morning wanting to blame something other than just getting a bit older. Not saying that you were, but let's get clearer information around it.
**Warwick:** The other thing that's really important, and people miss this a little bit, I don't want to punish you with these medications. My objective for you is for you to live as well as possible for as long as possible. And it just so happens that we've demonstrated by imaging your arteries that you've got a plaque at the distal point of your left main coronary artery. And that plaque is really, really important because if that plaque closes down, suddenly you will die. There is no question about that.
**Warwick:** And so our intensity to therapy, our desire to do something to modify that risk is a high intensity, which means we, you and I, have to work really hard to find a solution, the best solution for that.
**Brad:** I should also say that I'm on the Cartier.
**Warwick:** Yeah, don't stop that.
**Brad:** Yes, no, no, I've kept that going. And the only other thing I did stop, which was only a low dosage, I had Lovan, which is obviously non-related, and I've been on that for 20 plus years.
**Warwick:** What's Lovan?
**Brad:** Anxiety, depression.
**Warwick:** Okay. All right. So we've covered risk and benefit. That's really important. We want to come back and try and really establish if it's clear whether the statin or the ezetimibe or the combination is the problem. It is, I have to say, really uncommon for people to have problems with ezetimibe because it mainly stays in the gut. It really has its influence predominantly in the gut, so it's not really majorly absorbed. Doesn't mean you may not have had a side effect; it's relatively uncommon. But let's go back and re-explore that.
**Warwick:** The first thing is to get back on the pravastatin.
**Joan:** Sorry to interrupt. Brad said he normally took that in the evenings. Can he take it in the mornings?
**Warwick:** Yeah, I don't think it matters. But the pravastatin should be at night.
**Joan:** Oh, right.
**Warwick:** The pravastatin should be at night because the pravastatin is one of the earlier iterations of the cholesterol-lowering agents, which particularly... It has a shorter half-life, so that half-life means you need to take it when the liver's going to be most active, and that's in the evening when you're asleep but your liver's metabolizing busily.
**Brad:** That was another thing too, actually, just as I started talking about the liver. My urine at night was very, a few times towards the end, was very brown. Very dark.
**Warwick:** Yeah, and I thought, crikey, there's something more to what's going on. I don't have a good answer for that except it may be related to dehydration, but it may reoccur if you restart the ezetimibe and then we've got an answer. So let's work through that. I think that's really important.
**Warwick:** I think let's start with the pravastatin back on board. Let's do that. I'll get you back in maybe a month or so just with the pravastatin, and then we'll talk about reintroducing the ezetimibe or the ezetrol and see how you go with that. If we have issues with that, we've got other options, which might be to try an alternate statin. So pravastatin might be tried to another statin. And we've got newer agents, which you probably haven't tried, called rosuvastatin, which tends to be better tolerated.
**Warwick:** If the ezetimibe doesn't work, you ask quite reasonably, could we use alternate agents and things like nicotinic acid are possible? The other thing is that we now have available in Australia, though it's a... It's available on a private script, which means you have to pay for it, but we now have the option of these new agents which work through a different way, which is a PCSK9 inhibitor, which is a long way of saying it works through receptors that alter the LDL receptor.
**Warwick:** Now, they're pretty costly, but depending on what sort of response we get from your cholesterol lowering, you may not need the full dosage of those. You might be able to take a half or a quarter dosage, and we might be able to find a solution that works for you.
**Warwick:** I think the really good thing is that as part of this process, even though you were having side effects, you engaged your GP and then came and saw me soon to make sure that you weren't untreated and that you weren't not at least attending to those risks and not involved in the conversation to try and find a solution for them.
**Brad:** I said that to Brad. You have to go and talk about it, and you can't just stop.
**Warwick:** Absolutely. Some do. So I'm glad you didn't. Unless you've got any other comments, we might wrap it up there in terms of recording and stuff.
**Brad:** No, I think that's pretty well covered. There's always someone you miss, but you think of that after a conversation finishes.
**Warwick:** We'll do it on the next podcast. Thanks, guys. Really appreciate it.
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