Vytorin, Zetia and the ENHANCE Trial Hype

Ok, so by now, you probably have heard that Vytorin is a horrible drug and everyone should stop taking it.  Relax, while some parts of this study have shown to be harmful, we need to look deeper to see if Zetia (one of two drugs in Vytorin) actually has a harmful effect.

So, what was the study?  Well, take 720 people with familial hypercholesterolemia (they all had high cholesterol from their families) and randomize them to either receive high dose Zocor (80 mg a day) or Vytorin (80 mg of Zocor and 10 mg of Zetia a day).  Then, measure the carotid artery (the one in your neck) for diameter and see how much plaque has grown in the artery.  Less plaque leads to less cardiovascular events, right?  Well…

Ok, so the Vytorin (Zetia and Zocor together) group had an increase in plaque diameter of 0.0111 mm and the Zocor alone group their plaque grew by 0.0058 mm.  This may seem like a huge difference, but statistically it was not.  There was no statistical significance between these two numbers.  (p=0.29)  (WTF is that p number?  Basically if the numbers were actually different, and didn’t happen by chance, then the p value should be < 0.05  0.29 is not less than 0.05, and therefore not statistically significant difference.  Don’t worry about it.)  So basically yes, Vytorin did cause the plaque to grow faster than with just Zocor alone, but this could have happened by chance.

Now, the end-point in this study was the plaque, however, they did follow up on deaths, non-fatal heart attacks and non-fatal strokes, and so on and so on.  These are the numbers you are worried about when it comes to cholesterol.  Yes the drugs do lower cholesterol, but if you do not lead to less deaths and heart attacks, what does it matter, right?  So, we should find, according to the hype, that the people on Vytorin had more deaths, heart attacks and strokes, because, by gosh, their carotid arteries grew plaque faster, right?  Wrong…  There were no statistical difference between the two groups in deaths (0.6 % Vytorin vs. 0.3% Zocor), non-fatal heart attacks (0.8% vs. 0.6%) and non-fatal strokes (0.3% vs. 0.3%).  p=NS for all (there’s that darn p guy again.  NS?  that means not signifcant, or basically not <0.05, the magic number).  So, was there a value that there was actually a difference between the two groups?  Yep.  LDL (the bad cholesterol) was lowered greater in the Vytorin (Zocor/Zetia) group (58%) vs. the Zocor alone group (41%).  p<0.01.  (Damn you p guy!  Ok, since p value here was <0.05, then there is a significant difference between the two groups.  The only value (LDL) that was found to be significantly different between the two groups in this study.)

So, what could be concluded from this study, according to the outcome?  Yes, Vytorin was found not to have slowed down the progression of plaque build-up in the carotid arteries vs. Zocor in the study, but not by a great enough margin that it couldn’t have just happened by chance.  There was no difference between deaths, heart attacks, or strokes in the study (what we actually care about as an outcome, who cares if the patient has a 0.0053 mm more growth of plaque if it doesn’t do anything), and the bad cholesterol was actually lower in the Vytorin patients.  My conclusion is that Vytorin is a good drug at lowering cholesterol, but it has not been shown to reduce the risk of death or heart attacks (unlike Zocor, which has been proven to do so).  It may just not keep you from dying…So, what should you do if you are currently taking Vytorin?  Just keep taking it as prescribed by your doctor, and if your doctor asks you to switch medications, ask him if he has actually read the study.  

However, there is one thing I didn’t like about this study, and was its timing in getting the results.  This was a two year study that ended in April 2006, and because the drug company thought the public were going to freak out when the results came out (which it did) that the company (Merck & Schering) did not release the results until Jan 2008, nearly two years later.  They say it was because it was hard to calculate the results.  B.S.  You just didn’t want the people to stop taking Zetia, because the press would interpret the results incorrectly (which it did) and physicians would stop prescribing the medicine (which they did).  I wonder if all those physicians actually read the study, or just the New York Times. 

P.S.  Look!  Just another study that proves lowering cholesterol does not affect death rates, number of heart attacks or the prevalence of stroke.  Looks like there may be some hype in all of these cholesterol-lowering medications, but I guess that’s a topic for another post.  Funny how no one drew that conclusion from this study. 

Statins to help fight MRSA

You read it right. Statins, those great cholesterol lowering drugs like Lipitor and Zocor, may be the key to fighting methicillin resistant staph aureus, otherwise known as MRSA. MRSA is a superbug, a bacteria that we as humans and medical professionals have created by killing off all the other, easily killed bugs by weak medicines. This new superbug is one of probably many superbugs our children and grandchildren will be trying to kill. Now, however, a new drug has come into play, and it isn’t an antibiotic.

Bacteria, like you and me, use antioxidants, those great and wonderful compounds companies have been trying to put into everything from breads to sodas, to help fortify their defenses. The bad news, however, is that we don’t want them having defenses against our medicines. Special antioxidants, called carotenoids, are therefore used by the bacteria to produce a golden color of protection against our antibiotics. This same color is what gives carrots (hence carotenoids and beta-carotene) its color as well. So, why statins?

Well, before there were statins, in a lab, there were squalene synthase inhibitors. (Statins are HMG-CoA reductase inhibitors, but don’t try to keep up) These inhibitors worked against the same pathway that bacteria use to produce carotenoids and the golden barrier, if you will. Statins, however, worked so much better at lowering cholesterol than these guys did that statins took over the market. But, if we could give these squalene synthase inhibitors to humans, as well as antibiotics, we may soon have an answer to fighting MRSA. 5 years down the line, you say? No! Because, there have already been preliminary clinical trials in humans with these new drugs, of course, to treat LDL, not MRSA, they can be quickened through the process because Phase I and Phase II trials already exist, showing safety. I suspect we could have this in the market by late 2009-early 2010.

However, I do not recommend giving Lipitor or any statin to a family member you know who has a MRSA infection, as those are a different kind of inhibitors to cholesterol making, and will more than likely not work (I know, bad title…)