Look, Ma, No Vytorin! John McCain Switched Meds
30 CommentsBy Ed Silverman // May 23rd, 2008 // 10:09 pm
The Republican presidential candidate finally released his medical report and, not surprisingly, he takes a variety of meds - hydrochlorothiazide to prevent kidney stones; aspirin to ward off blood clots; Zyrtec for nasal allergies; Ambien CR, to help him sleep when traveling, and generic Zocor.
But McCain was taking Vytorin until earlier this year, when the Vytorin controversy erupted. And it worked. His cholesterol level was high in 2003, with a total of 226, LDL of 139 and HDL of 35. After Vytorin, the LDL dropped to the low 80s, but he was taken off the med after the results of the controversial Enhance trial were disclosed.
Instead, he was given simvastatin, or generic Zocor, which didn’t reduce his cholesterol by as much but was deemed “acceptable,” according to a press briefing. In fact, his LDL is up to 123.
Thanks to Shearings Got Plowed for the visual
condor
H I L A R I O U S !
Or perhaps it really will be reflective of market-erosion nationwide. . . . We’ll know next quarter, when Schering and Merck pony-up new numbers.
Now, from the sublime (Ed’s, above), to the TRULY-ridiculous (mine, below), on late-night Friday-night-fare, here — lighter stuff, by tradition — I’ve been attracting a truly-odd assortment of visitor-attention, of late. Take a look ["Damage Control"?! What?]:
http://shearlingsplowed.blogspot.com/2008/05/we-seem-to-be-attracting-oddest.html
condor
More of the ridiculous, now — this particular post of yours, above, struck me as emminently-ripe (perhaps over-ripe!) for a parody-campaign-button: “McCain for Generics 2008!”. . . .
So I baked some pixels this morning — feel free to take either the larger one, or the sized-down version (in my left margin matter), and repost as your graphic, here, or elsewhere, Sir Pharm-a-lot:
http://shearlingsplowed.blogspot.com/2008/05/probably-not-endorsement-wed-hoped-for.html
Have a great Memorial Day weekend, one and all!
Paul
Perfect example of how damaging Nissen hysteria can be. Here you have someone at high risk being treated with simvastatin plus zetia, i.e Vytorin, and doing well.
After the media frenzy, he gets switched to only simvastatin and his cholesterol goes back and is not at risk.
He was not at risk with Vytorin. All one can say is that the Enhance trial did not show what people thought it might show, i.e. some secondary marker of carotid intima media thickness.
The bottom line, the hysteria put this patient back at risk.
HorusCat
Paul,
You are absolutely right, and it just boggles my mind that physicians don’t seem to get it. Vytorin isn’t “dangerous” or “ineffective.” One trial failed to show significance, and everyone throws up their hands like the sky is falling.
I would be more worried about his HDLs than his LDLs at this point. He’s under 140; he’s not diabetic; he doesn’t have a history of MI or angina. Just put him on 10 mg of Lipitor and some niacin and forget about it.
Mark
“His cholesterol level was high in 2003, with a total of 226, LDL of 139 and HDL of 35.”
It was not “high”. It was actually below average even before he was put on medication. The average total cholesterol level for males in his age group in the pre-statin age was approx. 240 mg/dl. Average LDL was approx. 160, average LDL was around 35.
Mark
Correction: Average HDL was 35, sorry.
Atlex
Mark,
Below average doesn’t mean low risk. According to wire reports, other experts questioned about this suggested that his LDL should be <100 and recommended switching to a mor potent statin.
Atlex
Mark
@Atlex: Just be so kind and name me a single primary prevention trial that shows a noteworthy reduction of total mortality using cholesterol-lowering medications in a population including 70 year old men.
condor
I think the crux of our disagreement will boil down to “Why that particular goal level (LDL number)?”
I think it fair to say that for his advanced age, Senator McCain enjoys very robust cholesterol/heart health. Did you see his scores on the treadmill/stress test? Pretty impressive — for a guy his age.
That is the (very) good news.
Now, some clean-up, here: no evidence exists to equate gut-mechanism LDL lowering (the Vytorin/Zetia method) with better outcomes (fewer heart-attacks). All the data for outcomes is from statins, and earlier drugs. What’s the rush to spend so much more — for a questionable benefit, at best?
That is, “gut mechanisms” for LDL lowering (Vytorin) may — emphasis may — simply change/lower the number, without any real benefit to mortality risks.
Because Sen. McCain is so relatively-healthy, this may be a smaller concern for his case, but aren’t you all at all concerned that using Vytorin in all cases, aggressively, may lull patients into a false sense of security i.e., “my NUMBER is way low; that’s GREAT!” — so much so, that they stop eating a healthy diet, or stop exercising, and then suffer a cardiac event?
What if it just doesn’t work?
I think I would be concerned about that. What if Vytorin is like being “book smart” (a kid who tests really well on the ACT), but lacks “street-sense” — gets rolled, all the time, for lack of common sense (out well after midnight, alone, in a tough neighborhood — one he doesn’t know, at all — in a dark alley, on foot)?
That is why we must wait until 2012, at the earliest, to know whether Vytorin is worth all the extra money, and all that (circa 2006) fanfare.
Just my opinion, but it should be yours, too.
Justice in Michigan
I would be interested to hear any answer to Mark’s question above.
Takers?
Atlex
JiM,
I don’t fully disagree with Mark, but if the physician believes that lowering LDL is a worthy clinical goal for a 70+ year old male with a couple of risk factors, then they should use medication that meaningfully reduces LDL. Why take simvastatin in this instance and lower LDL from 139 to 123. What has this accomplished? Why take it at all? No doubt that the evidence for treatment in this case is debatable; some clinicians (maybe most) would buy into treating, some would not. However, if you are going to treat, then do it right and don’t waste resources and take the risk of side effects.
Atlex
Justice in Michigan
Hi Atlex - Went back to the report and found this as CV summary:
“3) Cardiovascular Fitness: He has no evidence of heart or other cardiovascular disease. He walked the Grand Canyon rim-to-rim in August 2006 without problems, and continues to hike whenever his schedule permits. His current stress echocardiogram is normal at a high level of exercise. There is no evidence of decreased blood supply to any part of his heart muscle. In the past he had slightly abnormal lipids, and now takes medication.”
So, besides being male, what are the risk factors?
I think the point of Mark’s question is what we have no studies at all that that suggest an advantage to more aggressive lowering of LDL for someone in JM’s condition, at his age, etc..
On the other hand, since he can apparently be temperamental and not always easy to work with, perhaps an antypical antipsychotic could be considered.
Paul
Everyone is missing the whole point of the discussion.
We’re not here to diagnose McCain’s health. the point of the discussion was on the histeria created around Vytorin.
His doctors had decided at some point that his risk was high enough to warrant simva+zetia (i.e. vytorin). He was well controlled, then here comes the histeria and he gets switched to only generic simva and his LDL goes back up, putting the patient at increased risk. Note I said “increased” risk not high absolute risk, because I don’t know.
Justice in Michigan
I hear you, Paul, and appreciate your bring us back to point.
Happened to find the snippet below in another context. So perhaps this is why JM but on Vytorin to begin with - his age at _that_ time, and possible BP issue.
Most of the docs I know have also switched _themselves_ off Vytorin in favor of statin-only tx, so I doubt we can blame “hysteria” as a major player.
*******************************
A cardiologist at Brigham and Women’s Hospital in Boston and an associate professor at Harvard Medical School, Christopher Cannon, not a member of McCain’s medical team, says McCain has a 22% risk of a heart attack or death in the next decade, based on data from the Framingham Heart Study. Doctors routinely use the study to calculate risk.
Eckstein, an internal medicine specialist who has treated McCain for 16 years, says there’s no medical reason why McCain shouldn’t be able to fulfill all the duties of president. Eckstein says McCain has “no evidence” of heart disease or other cardiovascular problems, has normal blood flow to his heart muscle and even walked the length of the Grand Canyon two years ago.
The records released Friday show that McCain stopped smoking in 1980 after smoking two packs a day for 25 years. The senator wrote about his youthful drinking exploits in his memoir Faith of My Fathers— including one episode where he fell through the screen door of a girlfriend’s house after too many beers. Today, his alcohol intake is “very infrequent: two drinks per month,” according to a note Eckstein made after McCain had a physical earlier this year.
Eckstein said in a press conference that he has advised McCain to decrease his salt intake, but said the senator does not have high blood pressure.
Cannon says three of McCain’s risk factors are reasons for concern:
• Although McCain is at a healthy weight — 5 feet, 9 inches tall and 163 pounds — the senator’s blood pressure, 134 over 84, qualifies him as a “prehypertensive.” That’s higher than ideal, but below the cutoff for high blood pressure, Cannon says.
• Eckstein said he recently doubled McCain’s dose of a drug called hydrochlorothiazide to treat kidney stones. But Cannon notes that this drug is also a diuretic and is commonly used as a first-choice treatment for blood pressure. If McCain needs the diuretic for his blood pressure, that would increase his heart risk even more, Cannon says.
• Cannon says McCain’s cholesterol should be lower, given the candidate’s blood pressure. McCain’s total cholesterol is 192 on a scale in which anything below 200 is considered healthy. His LDL, or “bad cholesterol,” is 123, while his HDL, or “good cholesterol,” is 42. According to national guidelines, a man with McCain’s other risk factors should have LDL of less than 100 and, ideally, no more than 70, Cannon says.
Paul
Let’s also keep in mind that all his doctors and political entourage want to spin his health as “fit to be president” no matter what. Who would be the idiot in his inner circle who would say there is a concern?
Good of Chris Cannon for pointing out that a man like McCain should have an LDL below 100.
Atlex
JiM,
Didn’t you answer your own question (Cannon’s comments)? McCain has multiple risk factors–male, age, hypertension. As Paul points out, the guidelines suggest an LDL of <100. He obviously needs a higher dose of simva or a change to Lipitor or Crestor to achieve that. I just don;t understand the value of lowering LDL from 139 to 123. Base on my layman’s understanding , this accomplishes little.
Atlex
Lisa Van S
Atlex,
Are you a Physician? Ahh,.. a layman’s understanding. Everyone is concerned about John Mc Cain, his meds and side effects,..benefits vs risks!! What about our young Men and Woman in the Military who are dying in their sleep due to Psychotropic drugs being prescribed Willy Nilly. It is Memorial day tomorrow,.. you know. For some its just another day of Barbecueing.
Paul
Lisa,
Nothing to do with what we’re talking about.
Mark
Paul: The guidelines were designed by 9 authors, 8 of which received money from the makers of Zetia/Vytorin:
http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04_disclose.htm#disclose
There is no scientific evidence that lowering LDL reduces total mortality in patients with McCains risk profile, not for Vytorin and not for Simvastatin.
Atlex
Thank you Paul for your attempt, but don’t count on having an impact. Everything with Lisa comes back to antipsychotics; nothing will change that.
Doc
Put him on Lipitor or Crestor. For all you amazed at his MD dropping his Vytorin, why so amazed? Merck and SGP have no one to blame but themselves for their “image”. There are other combos that will do the same as Vytorin.
Paul
Doc,
Lipitor and Crestor are very good but are not combos. They are both better at lowering TC and LDL (and raising HDL) a bit more than simvastatin alone, but not quite as good as simva+zetia, i.e. Vytorin. You could push the doses of Lipitor or Crestor high up to get the same effects but two things can happen, the HDL increases are less at the higher doses and you risk more AEs like increased enzymes, muscle pain, etc.
You are not wrong, L and C are good alternatives, but Vytorin is not a bad one.
Disclosure: I have cycled through all the statins. best that has worked for me, and without any problems, is Vytorin.
Justice in Michigan
Atlex - Yes, I added the bit from Cannon because it did suggest issues not otherwise in the report, and not mentioned by JM’s own docs. What can I say - I’m a fair guy!
Thanks for disclosure, Paul. I developed a permanent neuropathy on 5 mg. of Lipitor (!) but had 60% drop in LDL (to about 70), and significant increases in HDL, lowering of TC’s etc. So…different strokes (so to speak). And different CYPs.
But that’s why I also react a little stickily when I hear someone say, “just give him Lipitor,” etc.. It is rarely simple, even though I realize my own experience was unusual, and despite the fact that neuropathies are increasingly noted and recognized as not-incidental AEs for all statins.
Anyway, I don’t think there will be any debate that there is a place for many approaches, in whatever combos, etc., and also that we need much better data on the endpoints that count rather than all the surrogates, whether LDL, carotid appearance, etc.).
The part that I took issue with was the assumption that “hysteria” and Nissen were responsible for so many people switching off Vytorin. As noted, I know many docs who have done so, and they are not hysterionic types. And more folks than Nissen have advised Vytorin as a third-line option for _most_ pts, at this point.
Further disclosure - my own wife also uses Vytorin, and it seems to be a reasonable choice for her at this point.
Atlex
JiM,
Did you start on 1/2 a dose of Lipitor? I’m sure you are aware that the smallest pill available is 10mg.
Atlex
Justice in Michigan
I started at 10mg, as rx’d. Then split it when trouble began (within about six days) to 5 mg.. The split the 5mg yet again (to 2.5 mg) when trouble continued, hoping it would improve. It didn’t. So, after 2 1/2 weeks, Lipitor was history. I prioritized immediate nerve function over the odds of ending up on the wrong end of the 100 or so NNT.
I wasn’t taking anything else (meds or supplements) that I think could have competed on the metabolic pathway (I follow these things pretty carefully) so I think I must just be a very poor metabolizer of the drug. My guess is that the plasma levels were much higher than such dosing would suggest, which would also explain why I got such dramatic results in a short time.
Mark
@JiM: “also that we need much better data on the endpoints that count rather than all the surrogates”
There is a huge amount of data on Statins. Unfortunately, the primary prevention trials failed when you look at total mortality. More data won’t change this fact.
Atlex
JiM,
Your case demonstrates exactly why we need multiple drugs in each class despite the rantings of “experts” such as Marcia Angell. People react differently to different meds and need to have multiple options available.
Atlex
Justice in Michigan
Or it may demonstrate why we need pill splitters!
But, seriously, I agree. As discussed elsewhere on the ‘Lot, Prevacid, for example, does not have some of the interaction issues that the other PPIs have (and probably vice versa)
Whether I personally will be able to tolerate a different statin remains to be seen. Going on the CYP theory, prava may be next best try.
For Mark - I think there is still more to know re: primary prevention with statins. First, there are a range of permutations of age/gender/risk factors over time that I’m not sure we know about. Second, it is certainly possible that some of those who end up dying of cancer, or falling off a ladder, would have had a fatal MI earlier. While I agree that the primary prevention benefits have been oversold (and I have serious doubts re: NCEP guidelines), still more to learn, I think.
Prevention Doc
His medication regimen is a good economic one. If he has trouble with the simvastatin, his doc should consider pravastatin, the safest generic statin. For a little more LDL-C reduction coupled with an HDL-C increase, just add a little generic niacin at night. Cost savings are also to be had by taking generic Ambien at a fraction of the CR cost, given that the CR has really had mixed reviews and may not work as advertised. Even if he may not fit exactly into the “high risk” category, given his age, borderline blood pressure (on HCTZ) and stress level, he is likely to be best off with an LDL-C between 100 and 130 and an HDL-C of 40.
Piper
Prevention - Any patient that has “trouble” with simvastatin is probably going to fall into the same category of patient that has trouble adding “a little generic niacin” at night, despite how easy you make it sound. And I’m curious to know what constitutes a little. 1000mg? 1500mg? 2g is the recommended dose and not well tolerated.
What I found shocking about McCain’s doctor taking him off Vytorin (20/10) was not so much the poor logic used, but the even worse thought process that took place in putting him on simv 20. The lower the strength of the statin, the greater the comparative efficacy of the Zetia component in lowering LDL. In that regard, he should have expected the ~48% increase in LDL he got from March to May. Why didn’t he double the simvastatin dose to 40mg? His peers are reading about it right now and thinking, what was he thinking?