High-risk patients with multiple statin intolerances

[spacecowgirl]

What do you recommend for those patients?

QOD Crestor or Lipitor?
Adding CoQ10?
Non-statins - and which ones?
Change to lipophilic or hydro?

I have a patient like this I will be seeing and I don't know her dose history yet. She has intolerance to prava, atorva, rosouva and fluva. She's tried the statins I'd usually switch to already. No h/o fibrates, Zetia or WelChol though.

She needs about 45% LDL reduction (has DM, HTN, advanced age, FH). I'm leaning towards a QOD trial of Crestor at a low dose and titrating up +/- CoQ10 (some people swear by it) because of the statin pleotropic effects. Gemfib won't get her anywhere LDL-wise, but there is the Helsinki data. The only thing she is on is fish oil.

Thoughts? I'm seeing lots of these myalgia patients and they are challenging.

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[WVUPharm2007]

Nissen at TCC was once quoted as saying you should try every statin before you give up on the class. He's prolly one of the top cardiologists in the US...

 

[npage148]

I'll bite. Is it a self-reported intolerance or is she popping abnormal lab values. If she's whining of mild muscle aches, she needs some good old counseling. Did someone tell her friend tell her that she had muscles aches and had to stop? Go with the CO Q-10 and tell her these will make all her muscle pains go away. Then go with low dose pravastatin and tell her it can't get in her muscles and won't make them hurt.

 

[p-rog]

Ignorant pharm student's recommendation: 1) Ditch the fish oil (can increase LDL levels by up to 45%) 2) check lipids 3) If elevated, add non-statin (fibrate, BAS, or niacin- assuming DM is controlled). 4) avoid zetia unless all else fails.

That's what I would do if this was a pharmacotherapy test. Because you know, pharmacy school is exactly like real life.

 

[spacecowgirl]

Nissen at TCC was once quoted as saying you should try every statin before you give up on the class. He's prolly one of the top cardiologists in the US...

I guess there's still lova...

I'll bite. Is it a self-reported intolerance or is she popping abnormal lab values. If she's whining of mild muscle aches, she needs some good old counseling. Did someone tell her friend tell her that she had muscles aches and had to stop? Go with the CO Q-10 and tell her these will make all her muscle pains go away. Then go with low dose pravastatin and tell her it can't get in her muscles and won't make them hurt.

She's an anxious person already but that's beyond my scope She's never had any elevated enzymes, just pain in at little as 2 hours after taking a med up to a few months after starting. We had a really long discussion about her CV risk but she refuses to try another statin right now. I left her with several options to think about though.

I used to think it was all a bunch of whining but the more people I see that have myalgias, the more people I think really are just sensitive. which sucks when they have high CV event risk.

Ignorant pharm student's recommendation: 1) Ditch the fish oil (can increase LDL levels by up to 45%) 2) check lipids 3) If elevated, add non-statin (fibrate, BAS, or niacin- assuming DM is controlled). 4) avoid zetia unless all else fails.

That's what I would do if this was a pharmacotherapy test. Because you know, pharmacy school is exactly like real life.

I agree about the fish oil but why would you choose a non-statin and which one?

And school is nothing like real life, is it? *sigh*

 

[p-rog]

I agree about the fish oil but why would you choose a non-statin and which one?

And school is nothing like real life, is it? *sigh*

I don't know. I just figured after myalgia w/ that many statins, this person just can't handle them.

 

[PumpkinSmasher]

I don't know. I just figured after myalgia w/ that many statins, this person just can't handle them.

I would look to Niacin as the next option to lower LDL and boost HDL. Niacin may raise her glucose levels at high doses but you may have an easier time controlling the elevated glucose than you are having with controlling the elevated LDL. Cross your fingers she doesn't complain of myaglia on this as well.
Titrate slowly
I am off to bed but here is one trial:
http://archinte.ama-assn.org/cgi/content/full/162/14/1568

 

[Farmercyst]

Is she following any kind of lipid lowering diet/exercise regimen?

 

[npage148]

She's an anxious person already but that's beyond my scope She's never had any elevated enzymes, just pain in at little as 2 hours after taking a med up to a few months after starting. We had a really long discussion about her CV risk but she refuses to try another statin right now. I left her with several options to think about though.

I'd give up on any statin, she'll never take it. And the Flushing with Niacin will veto that. I'd probably go with a fibrate then add zetia and hope it does ok.

 

[Rumplestiltazepam]

e

 

[Old Timer]

I guess there's still lova...


She's an anxious person already but that's beyond my scope She's never had any elevated enzymes, just pain in at little as 2 hours after taking a med up to a few months after starting. We had a really long discussion about her CV risk but she refuses to try another statin right now. I left her with several options to think about though.

I used to think it was all a bunch of whining but the more people I see that have myalgias, the more people I think really are just sensitive. which sucks when they have high CV event risk.

Ask her if she pre-planned her funeral yet. This is the American nightmare. Side effect free full benefit therapy.
You must fully explain to her the risks of her course of action. Explain the value of statin therapy is proven in diabetics to reduce the incidence of a CV event by 1/3. It behooves her to try every single statin known to man to see if she can tolerate one of them. Ask her directly if she would trade a few days of muscle pain for 1/3 decrease in the likelihood of a heart attack. When people are obstinate, I usually become blunt.

 

[PumpkinSmasher]

You could always ask her if she is willing to try Colesevelam, since she is diabetic too. Yummy! Add on 2g of plant sterols, cholestoff. If a significant reduction does not occur in a couple months you could discuss trying a statin again and going QOD crestor/lipitor like you suggested or qd with low dose 10g lova/simva.

You can try to be more forceful about TLC as well.

 

[Glycerin]

And the Flushing with Niacin will veto that.

She could always take an aspirin (which she should be doing anyway) with the niacin to lessen the flushing.

 

[PumpkinSmasher]

She could always take an aspirin (which she should be doing anyway) with the niacin to lessen the flushing.

Taking the Niacin with a meal and starting with a low dose and titrating up slowly should help too. I am always surprised when people just cast niacin aside so quickly, it has a great efficacy profile and dosed correctly can have minimal side effects.

Glycerin, are you going to be at the OSHP conference November 7th for the NW residency showcase?

 

[Glycerin]

Glycerin, are you going to be at the OSHP conference November 7th for the NW residency showcase?

I'm not. That's my weekend to work. Boooo.

You?

 

[PumpkinSmasher]

I'm not. That's my weekend to work. Boooo.

You?

For sure. They are having a CV tutorial that I will definitely benefit from and I am unable to attend Midyear this year so a NW showcase is next best thing. In the next couple months, I will have to start choosing my 4th year rotations, so hopefully this conference will help me in my decision process.

I saved the letter of intent outline you posted a while back, much appreciated by the way!

 

[Farmercyst]

You could also try Red yeast rice to see if she gets the same statin-like side effects. Not sure what the dose equivalency would be, but it sounds like she's got no problem with carbs.

 

[PumpkinSmasher]

You could also try Red yeast rice to see if she gets the same statin-like side effects. Not sure what the dose equivalency would be, but it sounds like she's got no problem with carbs.

Most formulations: 600mg capsules = 2.4mg lovastatin. There is not much info out there, a few small studies dosing 1200mg BID. It is speculated the red yeast rice may have other monacolins besides the monacolin k that help block cholesterol synthesis.

 

[meister]

She should exercise, eat well, maintain a good weight, and have a glass of wine every night to bump up that HDL.

Of those four things, only one of them is probably likely to happen.

 

[Bradford]

I ran across this Q&A discussion in the People's Pharmacy.

Q: As a doctor who treats heart patients, I am thwarted by your unbalanced reporting about cholesterol-lowering drugs. In your column, you repeatedly emphasize the negative perceptions people have of statins rather than highlighting the benefits. These medications have a benefit-to-risk ratio of 400-to-1.
Muscle complaints were rare when these drugs were introduced, but now patients blame every ache and pain on their cholesterol drugs. And they tell all their family and friends about their problems. The vast majority of aches and pains that are blamed on statins are not due to the drugs themselves, but rather to mass-public hysteria, fed by word-of-mouth and fueled by the media.

A: Many people take statin-type drugs such as Crestor, Lipitor, Zocor and generic formulations (lovastatin, pravastatin, simvastatin, etc.) without problems. These medications are very effective for lowering cholesterol.
Side effects may not be as rare as you suggest, however. A review in the Annals of Internal Medicine (June 16, 2009) states that muscle pain affects up to 10 percent of those who try statins.
You believe that most people with statin-associated muscle pain are mistaken about the source of their discomfort. Research in the Canadian Medical Association Journal (July 7, 2009) reveals that many patients with muscle pain from statins have structural muscle injury identifiable in biopsies. The usual blood test for muscle breakdown is inadequate to detect this damage.

source -- http://www.peoplespharmacy.com/2009/10/04/doctor-objects-to-statin-bashing/

There were 16 comments to the Q&A discussion. Here is one:

Comment
Muscle complaints are far from rare when taking statin drugs as mentioned by a doctor. My husband was on zocor for three years when he had muscle myopathy. He could barely walk or feed himself. During the second year is when he complained of muscle aches and pain and dismissed the idea of statins being the cause. Since then, five neighbors in our community of thirty families have tried statins and all of them have stopped taking statins altogether due to myopathy.

When a doctor refuses to believe his patient when he complains and says to stay on statins for another six weeks, it is time to change doctors... this is exactly what happened to a friend of mine.

A veteran had been on lipitor for over a year and became bedridden for three months... he believed in his doctor until he read about others with the same complaints... sometime we have to become our own doctors, especially when doctors are not paying attention to their patients.

 

[Praziquantel86]

And your point? It's unfiltered garbage from a site that spews unfiltered garbage and passes it off as truth. I hope that someone has studied and published the increased morbidity as a direct result of reading that site. The People's Pharmacy is quite honestly a public health hazard.

 

[WVUPharm2007]

The internet is the best and worst thing ever created. Really, we don't grasp how amazing of an invention it is. We are living during a time in which the world is going to change like never before. Most people have never really stopped to think about what it all means and how SIGNIFICANT it all is.

And among those changes are, if you will, the democratization of accepted facts. Whatever the masses say is true becomes true. Mass hysteria trumps objective analysis. Plato once wrote that the thing he feared more than anything was democracy...he considered it only a smidgen better than tyranny. I see what he means. The internet is "empowering" people. Empowering them to think they know what the hell they are actually talking about when in fact they are clueless. It makes everyone an instant WebMD expert. Like the Armchair Quarterback of the digital age. The internet is allowing idiots to have a voice when they probably shouldn't. The above site is an example of such. And it IS a public health risk. Statins should be put in the damned water supply with fluorine they are so effective at preventing CV disease.

 

[spacecowgirl]

I'm going to see if she'll do the QOD Crestor or daily lova. Nothing else has outcomes data for primary prevention in women. Her LDL probably won't get to goal on the doses she can tolerate, but it seems like she'd be better on something than nothing.

If that doesn't work, I don't know what to try next. She already has IBS and chronic diarrhea so I think BAS are out, except possibly Welchol (no outcomes data). Zetia has no data, fenofibrate no data, gemfib and niacin maybe but I forsee intolerances to those.

Thanks for all the input.

 

[Thoughtfulsinner]

Who cares about treating high cholestero with medicationsl? Just exercise and eat right. It's pathetic how many scripts I see for statins.

 

[Priapism321]

I'm going to see if she'll do the QOD Crestor or daily lova. Nothing else has outcomes data for primary prevention in women. Her LDL probably won't get to goal on the doses she can tolerate, but it seems like she'd be better on something than nothing.

Thanks for all the input.

For what it is worth, I am not aware of any substantial data whatsoever when it comes to primary prevention in women with statin therapy. And, if you look at numbers needed to treat in the primary prevention trials (talking about absolute risk reduction, not the inflated relative numbers that are tossed around), it is actually a staggering amount of money and unnecessary toxicity to prevent a single cardiac event.

 

[spacecowgirl]

Who cares about treating high cholestero with medicationsl? Just exercise and eat right. It's pathetic how many scripts I see for statins.

Tell that to the skinny runner who just had an MI

For what it is worth, I am not aware of any substantial data whatsoever when it comes to primary prevention in women with statin therapy. And, if you look at numbers needed to treat in the primary prevention trials (talking about absolute risk reduction, not the inflated relative numbers that are tossed around), it is actually a staggering amount of money and unnecessary toxicity to prevent a single cardiac event.

CARDS, AFCAPS, and ASCOT-LLA had female subjects, not sure the % off-hand of females though.

NsNT do make you wonder why you treat people at all. But then it seems everyone > 75 in my city has metabolic syndrome and has had an MI already.

 

[Priapism321]

Tell that to the skinny runner who just had an MI


CARDS, AFCAPS, and ASCOT-LLA had female subjects, not sure the % off-hand of females though.

NsNT do make you wonder why you treat people at all. But then it seems everyone > 75 in my city has metabolic syndrome and has had an MI already.

CARDS 30%, ASCOT-LLA 19%, AFCAPS 15%

This is not considered substantial to me when we are talking about very low numbers of total events overall. I believe I have read a perspective piece by someone who actually obtained patient level data saying that in all the primary prevention trials, women had something like 20 - 30 events total. To me, not worth starting millions of otherwise healthy people on potentially dangerous agents.

 

[spacecowgirl]

To me, not worth starting millions of otherwise healthy people on potentially dangerous agents.

Like aspirin?

 

[Priapism321]

Like aspirin?

I forgot to add costly, potentially dangerous agents. And, although I have not crunched the numbers or reviewed the trials recently, I would be willing to bet that aspirin's NNT for primary prevention beats any of the famed statin medications.

 

[spacecowgirl]

I forgot to add costly, potentially dangerous agents. And, although I have not crunched the numbers or reviewed the trials recently, I would be willing to bet that aspirin's NNT for primary prevention beats any of the famed statin medications.

I think it's like >300, nope it's not. It's lower. I wonder which drug causes more costly side effects though? I don't know, I'm just thinking aloud.

 

[spacecowgirl]

Up-to-Date says ARR for primary prevention is < 5%, so NNT = >20, which is only slightly higher than the NNH (AR 1-4%) "the benefits outweigh the risks only when the risk of a cardiovascular event begins to exceed 5 to10 percent in ten years".

Secondary prevention is slightly better.

My grandma had a stroke shortly after being taken off of her simva by her NP ("she's so old, it's not helping"). It would have been one thing if she had just died, but now she can't do any ADLs by herself including eat. It sucks. Of course, there is absolutely no way of knowing why she had a stroke or if it had anything at all to do with being off of her statin. And we need to use evidence-based decision making, not anecdotal experience...but it does suck.

 

[Thoughtfulsinner]

Tell that to the skinny runner who just had an MI

The majority of those cases have some type of underlying heart disease (hypertrophic cardiomyopathy) unrelated to plaque buildup.

 

[meister]

Are we going to start an ASA 81mg QD discussion now? What do you PharmDs think of it anyway? Just curious.

 

[Old Timer]

So a diabetic patient who has an LDL of 180 or so should not get statins until after she has her first MI?????

 

[spacecowgirl]

The majority of those cases have some type of underlying heart disease (hypertrophic cardiomyopathy) unrelated to plaque buildup.

Ummm, no. Not people with a strong FH of heart disease or familial hypercholesterolemia You can have crappy lipids and be skinny. Or normal lipids and a high CRP.

Are we going to start an ASA 81mg QD discussion now? What do you PharmDs think of it anyway? Just curious.

I use 81 mg even though there is no difference in safety or efficacy vs. 325 mg. I recommend it in all diabetics > 40 or people with other risk factors. I follow the ADA guidelines because that's what our clinic uses.

So a diabetic patient who has an LDL of 180 or so should not get statins until after she has her first MI?????

Exactly.

 

[Pharmavixen]

From "Systematic review and meta-analysis of clinically relevant adverse events from HMG CoA reductase inhibitor trials worldwide from 1982 to present (June 2006)," Pharmacoepidemiology and Drug Safety 2007; 16: 132&#8211;143:

Results Over 86 000 study participants from 119 studies were included....Overall, discontinuation of statin therapy due to adverse events was no worse than placebo.

This study concludes that discontinuation of statins is due to behavioural factors rather than adverse events, and found no association of myalgia with statin use (with the exception of the studies of cerivastatin).

Then there's "Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,956 participants in 14 randomised trials of statins" Lancet 2005 366; 1267-78. This study found that statin therapy reduces 5 =yr incidence of major coronary events by about 1/5th per mmol/L reduction in LDL (it's a British study; that's about 40 in American units). The 5-year incidence of rhabdomyolysis was not statistically significant of statin versus placebo.

So you've got people attributing every tiny little ache and pain to their statin. A lot of you folks are young - I'm going to be 46 in a couple of wks and I'm in good shape, relatively speaking, but when you get to be over 35-40, when you do any activity exceeding your ordinary routine, you can have days of muscle aches. And actually, when rhabdo occurs, the pt may not even feel pain, instead experiencing extreme weakness.

I had this argument with my father in law, who was refusing to take his Lipitor with a TC of > 400 because he went on Medline Plus and read about rhabdo, and it scared him to death. I discussed risk versus benefit with him, and he was partly convinced (he's an educated guy, a retired chemical engineer), but it took some episodes of UA and getting rushed into the cath lab to have stents put in that won him over.

So you're seeing lots of people experiencing muscle aches because people commonly experience muscle aches.

 

[Thoughtfulsinner]

Ummm, no. Not people with a strong FH of heart disease or familial hypercholesterolemia QUOTE]Are you dense? Show me evidence where hypercholesterolemia was a cause of sudden death in an athlete.

http://www.suddendeathathletes.org/about_sdia.asp

 

[Thoughtfulsinner]

j

 

[spacecowgirl]

Ummm, no. Not people with a strong FH of heart disease or familial hypercholesterolemia

Are you dense? Show me evidence where hypercholesterolemia was a cause of sudden death in an athlete.

http://www.suddendeathathletes.org/about_sdia.asp

No, apparently you are the dense one. My point was that you can be fit and still die of an MI. But if you want to argue about it, I never said one thing about dying while running; I said a person can be a runner (eating right and exercising - your solutions for high cholesterol) but can have underlying risk factors that still cause them to have CVD. Not everyone with high cholesterol is some fat person who sits on their ass eating Krispy Kremes all day. That's all I was saying.

You are the one who made that leap to sudden death in athletes, not me. Thanks for the link though.

 

[spacecowgirl]

So you're seeing lots of people experiencing muscle aches because people commonly experience muscle aches.

I have seen that a lot. People that have DJD or OA attributing their back and knee pain to a statin. Then I will ask them if it feels flu-like and the answer is almost always no. Most of the people I'm seeing are older and do have muscle weakness related to age, not the medication but yet they are scared. I will talk to them about the risk of myalgias vs. the risk of rhabdo and how rhabdo can come from lots of other sources as well. Sometimes that makes them feel better, but some people are just too stuck on what they hear from their friends who have had problems.

 

[Thoughtfulsinner]

No, apparently you are the dense one. My point was that you can be fit and still die of an MI. But if you want to argue about it, I never said one thing about dying while running; I said a person can be a runner (eating right and exercising - your solutions for high cholesterol) but can have underlying risk factors that still cause them to have CVD. Not everyone with high cholesterol is some fat person who sits on their ass eating Krispy Kremes all day. That's all I was saying.

You are the one who made that leap to sudden death in athletes, not me. Thanks for the link though.

Just like someone who is on a statin can die from an MI. So I guess you really have no point then.

 

[Pharmavixen]

I have seen that a lot. People that have DJD or OA attributing their back and knee pain to a statin. Then I will ask them if it feels flu-like and the answer is almost always no. Most of the people I'm seeing are older and do have muscle weakness related to age, not the medication but yet they are scared. I will talk to them about the risk of myalgias vs. the risk of rhabdo and how rhabdo can come from lots of other sources as well. Sometimes that makes them feel better, but some people are just too stuck on what they hear from their friends who have had problems.

I use pretty much the same strategies when talking to pts. Another thing I say to people who complain of soreness is to ask them to think back and try and recall if they've been doing something out of the ordinary - doesn't always work, but sometimes it's yes, the pt's a 75 year old guy who put snow tires on his car himself, something like that.

My mum has been on statins for a while, and is fully cognizant of risks vs benefits, but commented that when she first went on them, every time she developed muscle aches from doing too much gardening or whatever, she'd think, is this it? Am I dying?

Unless I see evidence to the contrary, I'm convinced pts like described in O/P have problems that are supra-tentorial.

Hydrophilic statins are the least taken up by the muscles - cerivastatin was the most lipophilic statin ever synthesized.

 

[Farmercyst]

Just like someone who is on a statin can die from an MI. So I guess you really have no point then.

A person can die from water consumption, what's your point hwks?