Merck, Schering-Plough: Confessions of a Vytorin Patient

I am a computer scientist who is also Vytorin (a combination of Schering-Plough's (SGP) Zetia and Merck’s (MRK) Zocor) patient. After taking many different statins over 20+ years without success in lowering my cholesterol, I switched to Vytorin two years ago - it produced the best results ever, including amazingly low LDL.

When my health insurance attempted to deny coverage of Vytorin and recommended Zocor (another statin) instead, my doctor pointed out to them the need to combine Zocor with Zetia to be equivalent to Vytorin. They quickly agreed.

Now the economics -- 90 days of supply compares as follows: VYTORIN ( $245) vs. Zocor + Zetia ( $633). Even looking at generic alternatives for Zocor, the price for both is still >$400. When the insurance discovered that nothing was as cost-effective as Vytorin for my treatment needs, they have re-instated coverage in a hurry and presented an apology.

In summary, for those patients who want to avoid damaging their liver through high doses of statins, and consequently choose a combination of a statin +Zetia (and according to my doctor, there are plenty in this category), nothing beats Vytorin in convenience and economics.

The death of Vytorin and the hit on SGP has been grossly exaggerated. Does anyone believe that those who are on Vytorin already, will quickly switch out to other medications because of a botched-up panel discussion which proved nothing? I am surprised that neither SGP nor MRK executives asked that panel: “ Which statin has distinguished itself by unambiguously lowering plaque in the arteries?" If the answer is none, why then was Vytorin expected to accomplish that?

Bottom line: worst case scenario for Vytorin is that it won't grow its patient base for a while. Best case scenario is that the neophytes of the press will correct their collective hysteria and put Vytorin where it belongs - as another and most viable alternative to older statins.

Disclosure Author has a long position in SGP

Comments

[User 172200]

I have been on Zoccor alone 17 years with my LDH reduced to about 100 ( many lab tests etc) I switched to Vytorin about 2.5 years ago .... My LDH dropped from 100+ to 60.( I wanted to lower my LDH WITHOUT increasing statin dose for fear of liver or muscle complication) I am not going back to Zoccor . A mountain of medical research tells me, in effect, to lower the LDH as much as possible. Inference in article in Circulation, that it does not take high doses of statin to obtain anti inflammatory effects ( Circulation: 117:379-387.)

[misinformed media]

Amen to the above article.

[smith24]

Two Major Points that rarely get discussed are 1. The 720 patients in the enhance trial were predispose with high cholesterol and were statins users so their arteries were already cleaned out (one of the trial conclusionas as to why no reduction was seen with vytorin). 2. The technique used in measuring the artery in the neck is new and unproven (very difficult to do...especially to read the scans). I don't know why the trial didn't used naive patients. And Dr. Krumholtz (head of the panel at the ACC) should have know better that most people on statins don't reach their goals and with vytorin they do and it is much safer. I read an article that Dr. Krumholtz testified against Merck in the Vioxx litigation.
www.hispanicbusiness.com/news/2008/3/31/...

[Dr Bob]

Just because something 'makes sense' doesn't mean it works. While Vytorin lowers LDL cholesterol, the study showed that it DOES NOT have an additive effect to lower heart attack and stroke. Actually, the Zetia patients had more carotid artery disease in spite of the lower cholesterol.

Generic Zocor (simvastatin) is 80-90 cents a pill, versus $3.22 for Vytorin.

One must ask: is it worth taking a pill that costs 3x's as much for no measurable beneficial effect? One analogy - do you put premium gas in a car that runs on regular?

[WaveNet Pharma]

Dr. Bob -- sorry you missed completely my point.
The differentiator in Vytorin is Zetia -- everyone, including the ACC panel which managed to masquarade this botched-up analysis as "scientific" agrees : because of Zetia, LDL is lower for everyone tested without causing the unwanted liver complications of higher-dose statins.

Now, the economics... I've just told you facts in hand that generic Zocor+Zetia is MORE expensive than its equivalent Vytorin. One must ask : if premium gas is cheaper than regular, which do you put in your car ????

[User 172200]

Still ANOTHER interesting article - AJC :june 15.'07:1706-1713 - "In conclusion, the lipid modulating and anti-inflammatory effects of ezetimibe/simvastatin provide ADDITIONAL benefits NOT realized by statin monotherapy alone" As far as "proof" that Vytorin lessons the incidence of heart attacks & strokes: I feel it could be reasonably assumed from the literature, that a medication both having the statin anti-inflammatory AND LDH lowering effects should be cardiovascular protective (like the different brands of aspirin) No doubt follow up research will substantiate this point. Disclosure I am an MD with NO relevant pharma holdings.

[User 172200]

Enter your comment here Additional comment: - Interesting that the Cardiologists participating in the New England Journal of Medicine articles conclude in effect : - If your present medication is not effective in lowering your LDH - THEN Vytorin is recommended. ( My interpretation of this "double speak" : - Vytorin is a superior medication! )

[chemist10]

Without a doubt this had to be one of the dumbest trials ever conceived. It was like trying to hit a moving target with a stationary gun. Stupid !! I was on lipitor for years and never had cholesterol below 200 on 10 milligrams (I didn't want a higher dose of any statin). Vytorin reduced my cholesterol to 130. Unfortunately it doesn't affect HDL, only LDL, and this is what it did in the trial. It lowed LDL better than Zocor alone and there were no safety issues. I don't plan on using anything else.

[Dr. Josh]

It is always amazing to me how funny some people are. Between the guy who persist on trying to lower his "LDH" and the author who is too blinded by his long position in SGP to take his health into consideration. People seem to disregard CIMT as a surrogate, and focus on LDL which is also of course a surrogate- just a weaker one. There are multiple examples of drugs which lower LDL- or LDH if you prefer- and increase your risk of MI. These include oral contraceptive and torceptrapib.
A few factual points:
1- The author compares the cost of vytorin to the cost of generic zocor(simva) plus zetia. The more appropriate comparision would be to generic simva- which would of course be much cheaper. Since this trial suggests that zetia is in fact a glorified placebo.
2- Not all of the patients in this trial had been on statins. 19% were statin naive. Subset analysis didn't show any difference in these patients. Subset analysis also didn't show any different results in those patients with thicker IMTs. It was these subsets analyses which really cripple the whole argument that MRK/SGP and their stockholders who are posting above are trying to make.
3- This trial didn't prove safety. It was not an endpoint trial. There were not marked more adverse outcomes in the vytorin arm- That is a very different thing. The drug may well be dangerous and we will have to wait for the large multi-center trial to know that.
4- In response to the original post- Crestor has unambiguously descreased plaque in arteries- both in the carotids and the coronaries, by CIMT, IVUS, and QCA. Lipitor has been also shown to decrease plaque progression compared to placebo- even in population much like the one studied in ENHANCE. See the ASAP trial
The better question is which cholesterol drugs have been proved unambiguously to prevent heart attacks. The answer to that question is Simvastatin, Pravachol, Lipitor, Crestor, Mevacor, Gemfibrozil, Niaspan. Really everything except Zetia, vytorin and tricor. It is that question that guides my choice of therapy. I would think that from a patient perspective in might be more important too.
Disclosure: I am a cardiologist who shorted MRK and SGP on Friday and bought AZN on Monday. (Which I guess means I won) Currently though, no position either long or short in MRK or SGP.

[User 172200]

DR JOSH ! Welcome! Hey ! Your own guys ( NEJM Articles) when "pushed by the facts", recommend to their patients Vytorin if their previous medication was ineffective in LDH lowering !! Hey (again !) YOU should know ( As I certainly do, being an MD) that there ARE out there, a hell of a lot of folks that don't tolerate increased statin dosage! Like chemist10 & others I enjoy the relative safety with Vytorin of having my LDH at 60 ( from 100+ after years on Zoccor 40mg alone. Please also read the AJC article ( June 15, 2007) referred to above !!

[Dr. Josh]

If you look at the trial that Merck/SGP did comparing Crestor to Vytorin, you will notice that there were actually more side effects in the vytorin group.
In patients who can't reach goal on a statin, or cant tolerate a statin, I would add Niaspan, a fibrate, a resin binding agent, and dietary changes and if these all failed I would consider under Zetia- realizing that I am probably just treating my own need to longer lipids and that this intervention is probably not helping the patient.
If I were WAVENET's doctor, I would switch him to crestor, which would acheive the same LDL reduction, same level of side effects, same cost, but with actual positive trials for both surrogate endpoints and mordibity.
I would also refer you to an article two years ago- in JACC I beleive- which compared 10 of simva to 10 of zetia. Both acheived the same LDL reduction, but Zetia failed to have positive changes in flow mediated vasoreactivity- a measure of vascular health.
I can't see any reason to opt for vytorin as a first, second, or third line drug. Fourth line is debatable.

[WaveNet Pharma]

Dr. Josh

You have assumed that I haven't tried other simvastatins before and that I haven't tried exercise, dietary changes and other supplements to lower my lipid panel indicators. I am sorry to disappoint your brilliant analysis , but wrong on all counts. 26 years of a patient's own experience and records is behind my decision to stick with Vytorin.

The only thing that worked for me so far is Vytorin and this is because of Zetia and not Zocor. ( The latter was no better than Lipitor or Mevacor or Pravachol, all of which I've tried.). Something that you and some other MD's insist to overlook.

Why are you suggesting that Zetia's presumed lack of comparative vasoreactivity is more dangerous than a very high LDL when it comes to morbidity ? Do you have any scientifically acceptable proof that this is the case ?

At least in my scientific world, when we don't know what we don't know we keep our opinions to ourselves....

[User 172200]

Dr Josh ! Yeah .... well Enough of this dueling over silliness .... Once your LDH settles out at 60 or below you reach such a sublime a feeling of WELLNESS ... Just hard to describe ... Like levitating ..... The only challenge remaining is to try and convince others to experience the same !!

[User 1224]

Dr. Josh,
glorified placebo? Since when does placebo significantly lower TC, LDL, TG, CRP , non-HDL cholesterol, and APO-B more than Zocor? I must have missed that study!
Trials with Pravachol, a drug with excellent outcomes data, have shown increases in IMT. The most recent Lipitor IMT trial (RADIANCE) failed to show any significant change in IMT with Lipitor 80. Where was your reference of that trial? Crestor used much different patients, with much thicker baseline IMTs and significantly lower LDLs, in their studies.
Crestor has shown decreased plaque and decreased CV events vs. placebo, hardly earth shattering. Why didn't they use an active comparator such as the much cheaper simvastatin? What proof is there that it is better than the generics other than in reducing LDL and CRP? If it is no better than simva or prava at reducing events why not stick with them for $5 a month? Or maybe you really do believe that further lowering LDL, TG, APO-B, & CRP play a role in reducing events.

[Dr. Josh]

I beleive that higher doses of more potent statin are better than lower doses of less potent statin at preventing cardiac events. This has been shown repeatedly. Whether LDL, TG, APO-B or CRP numbers are important or just epiphenoma, we dont really know at this point. Certainly there are compound which treat these numbers and show no benefit. The most obvious example is torceptrapib. (I suspect zetia will be put in the same category when we know for sure in 2012.)
Placebo actual does lower all of the things you mentioned in various studies- but that really isn't the point.
You seem to be quite confused in your reference to Radiance. This was a trial of torceptrapib with lipitor as the baseline in both arms. I don't see what this says about lipitors effectiveness. That would be like trying to say that zocor was ineffective from Enhance.
@ Wavenet- There is no proof that Zetia is either good for you or bad for you. All we know is that it lowers LDL( a surrogate) and seems to cause a trend to more IMT thinkening in familial hypercholesterolemic patient population than placebo- and that we know it is rather expensive. So I would turn the question on you and ask- Do you have any scientifically acceptable proof that this compound decreases morbidity? Given the lack of proof, I would again suggest you consider Crestor or Lipitor plus niaspan. ( all of which do have this proof.)

[gratianus]

I'm an SGP shareholder. I don't take Zetia or Vytorin but a generic statin that does a fine job of supressing my LDL. As a shareholder I find almost everything expressed above--even the comments critical of the products' broad use--encouraging, since there obviously is a continuing need for these drugs even if the panel's and the NEJM's editorials were to be substantiated by subsequent studies. The point as an investor is that at current prices there seem to be absolutely no revenues or profits factored into SGP's share price. If there is continued revenue, even attenuated as it will be, the market is grossly misreading Schering's position.
Though I wonder about how the data was presented at the ACC meeting, I'm not surprised by the hysterical media reporting or the market's Henny Penney response. Let's see where SGP is six months from now.

[WaveNet Pharma]

Finally Dr. Josh has admitted that he does NOT know whether Zetia is good or bad, and won't until 2012.
Conversely, I do know that the statins I have tried did not lower my cholesterol and when taken in higher doses affected my liver -- which led my doctor to advise me to stop using them. (i.e. it was bad for me.)

In view of my experimentation over so many years, I have found that Vytorin is the drug that works for me and have no intention of switching unless and until proven that it is as bad for me as the statins you seem to be favoring. As to your comment on costs, again check your numbers once and for all : if you must buy Zetia with another statin ( any) , Vytorin contains both and is a cheaper alternative.

It was nice getting your views on the topic, but I would still like to see you admititng that Vytorin, for a certain patient population, is yet another alternative to treating high-cholesterol efficiently and economically.

[Andrew]

Learned a lot from the discussions above. Most importantly, I now know why I always have to wait 10-20 minutes in the examination rooms to see the Dr..........because he/she is posting on investment websites during office hours! LOL!

Just for reference, can anyone give treatment cost for a branded monotherapy statin, such as Lipitor? (actual question)

[Vytorin User]

I concur with WaneNet, as I have an almost exact historical experience. It lowered my bad numbers, raised my good ones and lowered my triglycerides. NONE of the other statins did any good for me. I've never heard of plaque removal as the benchmark for success in any of the other drugs. I bought size in the convertible preferred after it collapsed at ~ 150. I'll get > 9% yield, and most of the upside as this gets worked out. I would also point out that a takeover is a distinct probability. They have one of the best pipelines / stock price extant. Shorts will get creamed on this one.

[User 172200]

Plaque REMOVAL ? My understanding : - The pathologic sequence that eventually causes severe artery narrowing, then occlusion, occurs in stages and over extended periods of time. Some of this "build up" involves an interruption of the endothelial - intimal surface by cholesterol and associated inflammatory tissue that becomes progressively more chronic over time, narrowing the lumen and in some instances calcifying. The latter described effects would not seem reversible. It would, therefore, seem that statins work by prevention of the inciting inflammation and inflammatory sequelae. Apparently, there is some evidence of clearance in some cases of more recent acute atheroma build up if the statin dosage is quite high and therefore putting the patient at some increased risk. Summing up : - We're back to the prime current indication for medication use - to reduce the LDH to as LOW a level possible WITHOUT putting the patient at risk . VYTORIN is certainly one medication that accomplishs this quite effectively for large numbers of patients that have been taking it !

[Ertop]

What if we discover something what reduce LDL to 0 (zero)? That is not a race. We do not treat lab results. There is the (still) living patient behind.

[bmc]

What this trial shows is that having a LDL level of 193 or 141 (down from 320) makes no difference with respect to your chances of getting a CVD or increased IMT. This calls into question the reliability of LDL as an indicator of CVD risk. Ergo, it indicates that it makes no sense to try to lower it, because if LDL is not an indicator, it can even less be the *cause* of CVD.
If previous trials showed a relationship between LDL level and CVD risk, this trial clearly contradicts them. The scientific method requires for the previous trials to be reviewed very thoroughly, and for new, more sophisticated, higher resolution trials to be carried out if no flaws can be found in the old trials nor in this one. Saying that if Vytorin does not work we should go back to Zocor is not science, it is not medicine but thaumaturgy.

[WaveNet Pharma]

You made a good point, bmc.
There are some fundamental assumptions that need to be questioned.
Until then, moving from Vytorin to Zocor makes no sense at all.