Vytorin - What’s the Hype About?
Barbara Walters wears Chanel suits. She is so meticulous coiffed that she makes Botox models look like wrinkled shirts. She does not talk about with whom she would have a ménage a trios, but NOOO on The View her co-host asked her this question! Ugh, what is wrong with the media?
I think the news has a responsibility to report accurate and fair information because the news affects us. However, in our shock-value society, it seems the news is pushing the envelope all the time to get the public to tune in. Avandia got bad press last year, and though none of my Avandia-taking patients ever had a heart attack, quite a few stopped taking it because of fear spread by the news. Now these patients have high sugars and many have started insulin as a result. But you don’t hear the news reporting how people with uncontrolled diabetes lose their vision…as well as their feet…and die of—guess what? Heart attacks!
Sure I understand that not all meds are safe, but Americans are living longer lives because of modern advances in medicines. It is definitely not due to better self-care. When was the last time you exercised and ate fresh vegetables?
So now I have been bombarded by patients and fans about Vytorin, a cholesterol lowering medication. January 14, 2008 the news told the world about the ENHANCE trial. Unfortunately, the study has not been made available to physicians so we can fully understand it…which puts us at a major disadvantage to take good care of our patients. So I became a normal citizen and gathered information the best I could on the internet. This is what I know so far.
Back in 2001, the ASAP trial looked at people with a rare genetic disorder: Heterozygous Familial Hypercholesterolemia. Lipitor 80mg and Zocor 40mg were compared to see a reduction in carotid intima media artery thickness (IMT). (IMT is a predictor of coronary artery disease.) In the end, Lipitor was successful in reducing the IMT but Zocor failed and actually had slight increase in IMT.
Now the ENHANCE trial basically did the same study as in the ASAP, but compared simvastatin 80mg (aka Zocor) and Vytorin, a “combo” pill (without the soda and fries) of simvastatin 80mg and Zetia 10mg. These folks with Heterozygous Familial Hypercholesterolemia on average had an LDL of 318. LDL is the bad cholesterol, and in general most un-medicated patients I have don’t have an LDL more than 200. So an LDL of 318 is higher than Nicole Richie off the wagon!
The IMT baseline means were 0.68mm (Vytorin group) and 0.69mm (simvastatin group) and 2 yrs later after treatment were 0.6911 (Vytorin) and 0.6958 (simvastatin) that were not statistically different. For every 0.10mm increase in carotid IMT, there is a 15% increased risk of heart attack and 18% increased risk of stroke. In ENHANCE there were increased IMT of 0.0111 (Vytorin) and 0.0058 (simvastatin). Also there weren’t more heart attacks, strokes or deaths in either group. So does this study deserve all the hype?
Why did they do this study? I have no idea because the Heart Protection Study was an excellent trial that showed simvastatin reduced cardiovascular deaths, and aren’t we more concerned about that vs. carotid IMT? So they should have done an outcome study with Vytorin to see if it saves lives, in my humble opinion.
I find it amazing how there are a billion unregulated products out there to make you lose 700 pounds and give you more energy than a solar powered house on the equator, but Dr. Steven Nissen and the rest of the media instead appear to be focused on scaring patients. It makes me want to cry…and Barbara Walters wouldn’t even have to interview me.
(c) Dr. John Hong, Inc
Notes: Vytorin has been in the news since January 14, 2008 due to the announcement of the ENHANCE trial. Vytorin is a combo pill of simvastatin (Brand name was Zocor) and Zetia. Simvastatin was shown in the Heart Protection to reduce cardiovascular deaths. However, Zetia has not been proven to reduce heart attack, strokes, or cardiovascular deaths. But Zetia has been shown to lower LDL – bad cholesterol that is associated with cardiovascular disease.
Back in 2001 a medical journal (Lancet) published the ASAP trial. It looked at a rare population of people with Heterozygous Familial Hypercholesterolemia, a genetic disorder seen in 0.2% of people with high cholesterol. The ENHANCE trial looked at the same group of folks. In the ASAP trial Zocor and Lipitor were compared to see reduction in carotid intima media artery thickness (IMT). IMT is measured simply by ultrasound. It is a clinical predictor of coronary artery disease. I never understood this study because the dose of Lipitor was 80mg (the highest dose) but Zocor was 40mg (though 80mg is the highest dose). So in the end of ASAP, Lipitor reduced IMT (which is good) but Zocor showed an increase in IMT (bad).
The ENHANCE trial basically did the same study as the ASAP but compared simvastatin (AKA Zocor) vs. Vytorin. This time though, the ENHANCE used 80mg of Zocor instead of 40mg in ASAP. Also the Vytorin group got the standard 10mg of Zetia and 80mg of Zocor.
The 720 folks with Heterozygous Familial Hypercholesterolemia had really high LDL levels, way higher than most people have. I would say in my practice, a person with an LDL 200 or more is pretty unusual. In the ENHANCE trial the average LDL at the start of the study was 319 in the group whom received Vytorin and 318 in the simvastatin group. Pretty darn high—ouch!
The IMT baseline means were 0.68mm (Vytorin group) and 0.69mm (simvastatin group). After 2 years of the trial, there was an increase of 0.0111mm in Vytorin group and 0.0058 in simvastatin group. If I did my math right, that means the end mean IMTs were 0.6911 in Vytorin and 0.6958 in simvastatin. Statistically it was not significant meaning they were basically the same from what we can tell. What is normal carotid IMT? It depends on your age, sex, and risk factors. Also I don’t know if they did this study in kids or not. Sigh.
So what does the IMT increase mean? The inner layer of the artery can become plump from cholesterol buildup. For adults, there is a moderate graded positive association between the carotid IMT and CAD (coronary artery disease). A meta-analysis of 8 studies showed: 15% increased risk of heart attack and 18% increased risk of stroke for every 0.10mm increase in carotid IMT.
Now I don’t have the real paper article. Because of the MEDIA not waiting for physicians to be able to critically appraise the study, I am forced to make my assessment from the literature in the papers, including Merck/Schering-Plough, CNN, AHA, and ACC. It doesn’t look like Vytorin is a dangerous drug compared to a plain statin like simvastatin alone and we have always known a very small increased risk of liver toxicity (2.8% Vytorin vs. 2.2% simvastatin) and muscle breakdown (2.2% Vytorin and 1.1% simvastatin). The problem is…how does this relate to reducing real heart attack and strokes in people who don’t have a genetic high cholesterol disorder as in the ENHANCE study? I don’t know. There isn’t a research trial to show this. I will say it is not great news the IMT didn’t improve but got worse with both simvastatin and Vytorin. But then again in the ASAP simvastatin had worsening IMT but the Heart Protection Study shows the benefits of simvastatin. This to me means more research needs to be done, but at this point it won’t make me take anyone off Vytorin and Zetia or stop it in my patients.
