Zetia now available as the generic ezetimibe first became available in 2002 as a cholesterol lowering drug. With its quite unique mechanism of action, Zetia reduces absorption of cholesterol from the small intestine. The more popular statin family including Zocor, Lipitor, Pravachol and Crestor works within the liver cell to halt cholesterol production.
Hello dr. ken landau thanks for watching let’s talk about zetia zetia or ezetimibe that’s a drug that was approved by the food and drug administration in 2002 to reduce the absorption of cholesterol from the small intestine it could be purchased by itself or it could be combined with a statin for instance vytorin is 10 milligrams of zetia and 40 milligrams of the
Statin known either as oak or or simvastatin it was also sold for a while between 2013 2015 combined with the tour of the statin that didn’t seem to be much of a seller now the first thing you should do if your cholesterol is elevated if your bad cholesterol the ldl is elevated you should change your lifestyle you should eat better you should reduce your weight you
Should get more physical activity and even though people say they’ve tried you haven’t tried hard enough you haven’t changed your diet appropriately now how does that work well it’s said to work as i mentioned by reducing the cholesterol uptake but it also has been claimed to be an antioxidant anti-inflammatory drug who reduced the insulin resistance work against
Type that clumping preventing blood clots and reducing the high sensitivity crp the c-reactive protein well it’s going to decrease the cholesterol absorption by that 50% by targeting a particular enzyme and it’s also going to decrease the cholesterol delivery to the liver decrease the cholesterol synthesis in the liver deplete delivers stores of the ldl that’s
The bad cholesterol up regulate the ldl receptors on the surface of the liver cells so that the liver cells are going to gobble up some of the extra ldl that’s circulating around in your bloodstream and supposedly all that is going to lead to a reduction in ldl and then you live happily ever after at least so the same goes so it’s going to do crease your bad
Cholesterol ldl decrease the total cholesterol decrease the applebee decrease your triglycerides and it’s supposed to increase your hdl just the smidgen so if we look at about two weeks worth of therapy it’s going to decrease the ldl somewhere between 12 and 20 percent decrease the triglycerides by seven to 10 percent decrease the cholesterol total cholesterol by
Maybe about twelve percent well let’s look at combining it now with the simvastatin so if we look at zetia plus simvastatin what’s going to happen let’s talk about the ldl well if we use the zeti by itself the ldl might decrease by as much as 19 percent zocor the simplest adhan might push the ldl down 27 percent but if you combine the two together it could drop the
Ldl by about 50 percent if we look at the triglycerides triglycerides with debía alone fall by about 11 percent followed by another 14 percent with the simvastatin combine the two together and we get a 26 percent reduction but so what that’s just a number the real issue is does it reduce the likelihood that you’re going to have some kind of cardiovascular event
Or die from a cardiovascular event and the fda on the package insert says the effect of zetia on cardiovascular mortality morbidity has not been determined well they came out with a study in 2008 at least that was published in 2008 it’s called the enhanced trial it looked at people who had genetic abnormalities that led to elevated cholesterol and it was found
That there was no benefit repeat no benefit of adding zetia to the sin of the statin there was no decrease in the heart attack no decrease in the stroke and as a matter of fact it seemed to increase the a deposition of plaque in the artery ole wall well actually the study was completed in 2006 that was just published in the new england journal in 2008 and it was
Only published after continued pressure by the medical community to get the thing published because the major pharmaceutical companies were kind of reluctant because the drug was a cash cow it was bringing in about four billion dollars in sales and the study showed that the drug didn’t seem to reduce the cardiovascular mortality or morbidity so at least according
To dr. steve nessun who is one of the pioneers in cardiovascular medicine and chief at the cleveland clinic he’s just said there isn’t any evidence to add zetia to simvastatin doesn’t produce any advantage 2015 there was a meta-analysis looking at all of the studies that had been published looking at ze a– with the simvastatin just combined or looking at that
Versus the simvastatin by itself for any statin by itself and actually there was no benefit again to adding the zetia to the statin drug there was no benefit from all cause mortality no benefit from cardiovascular disease related death or non cardiovascular disease related death or heart attacks or cancer or even stroke so we don’t really care what the number is we
Care what the outcome is well most recently there was another study it was published again in the new england journal of medicine just in june of 2015 it was called improve it it was funded by merck improve it looked at 18,000 individuals now cardiovascular disease is pretty common and high ldl is pretty common but for them to get 18,000 individuals on the study
It took 1140 seven different sites throughout the world in 39 countries in countries like turkey and ukraine and africa slovakia india and hungary in ecuador and colombia and estonia and brazil and chile to get some data on these 18,000 people the 18,000 people were high risk patients they were high risk they had unstable angina or they had recently had a heart
Attack their ldl at the beginning of the standing study was somewhere between 50 and 100 that’s pretty good if they were on a statin if they weren’t on a statin it was between 50 and 125 still pretty doggone good the patients were given either the zocor by itself 40 milligrams or given zetia plus 40 milligrams of zocor and these people had significant cardiovascular
Disease as i mentioned they were recently hospitalized and the study evaluated the outcomes it was a six-year study and they looked at a combination endpoint so if you had either cardiovascular disease related death or a non-fatal heart attack non-fatal stroke or you had to have revascularisation because of unstable angina well you were considered to make an
Endpoint but even during the study they changed the protocol they amended the protocol five times that’s not very good that’s like changing the book as you’re reading it you don’t do that you set the guidelines and then you follow the guidelines but what was the end result of the study well according to the study there was a major improvement in cardiovascular
Outcomes if we look at the combination group the group received the zetia and the statin the incidence of that primary event was 32.7% if we look at people who received a zocor alone well 34.7% of those people reached that primary endpoint in other words had some kind of an event so that absolute difference was only two percent and the benefits didn’t even occur
Until after the first year and if we look at the lowering of the ldl or the bad cholesterol yes it was lowered a little bit more he took the combination medicine it was about 50 for your bad cholesterol it took just the zocor it was about 69 well again we don’t really care what the numbers are what’s the difference as far as the cardiovascular outcomes are concerned
No difference in all cause mortality cardiovascular related disease death no change in the incidence of death from coronary heart disease fatal heart attack hemorrhagic stroke revascularisation hospitalization for unstable angina there was a smidgen of a difference in non-fatal heart attacks and a little more than 1/2 of 1% difference in the incidence of ischemic
Stroke stroke but overall here’s the kicker there was no statistically significant improvement in people receiving the zetia plus the statin versus the statin alone if you were a man if you were less than 75 years old if you were non caucasian and if you were caucasian there was only a smidgen of a benefit there wasn’t any benefit if you were diabetic if you were a
Current smoker and just the smidgen of a benefit if you were a nonsmoker no benefit if you had normal blood pressure if you had hypertension a smidgen of a benefit improve it even with the drug company involvement even with very high-risk patients even with very low ldl there was still no significant benefit it mirrored the results of the trial that we talked about
A few moments ago that they finished in 2006 and hid until 2008 but remember the companies were making a significant amount of money from the drug well if we look at the surrogate markers and that’s what so many of these studies do they look at the ldl that total cholesterol the triglycerides and you get so excited because you say oh my goodness it made the numbers
Go down but who cares who cares we care as far as what is the outcome do you have fewer heart attacks yeah fewer strokes yeah need less revascularisation and at least at the present time that would appear that the drug doesn’t cut it now remember i said the package insert said the effect of zetia on cardiovascular mortality and morbidity has not been determined
Well with the results of improvement the study that just came out in 2015 the company went to the fda and said hey why don’t you say that one of the indications is that this drug can decrease the risk of cardiovascular events it can decrease the risk of heart attack and stroke and cardiovascular related disease death fda thought about it for about a moment and said
You know the study is too small and it’s limited to certain patients and it really doesn’t cut it so no we won’t change the package insert well how do you take the drug it’s an oral drug you can take it with or without food the peak absorption is somewhere between about 4 and 12 hours it’s metabolized in the small intestine and the liver the half-life of the drug
Is about 22 hours so you only have to take it once a day you don’t have any good information that it’s safe for pregnant women or nursing women certainly if you have active liver disease or moderate to severe chronic liver disease it shouldn’t take this drug if you have unexplained elevation of your liver function tests don’t take the drug there’s no issue with
Kidney disease side effects are really not significant remember the statin drugs are associated with the muscle pain not so with zeti it’s not toxic to the muscle no rhabdomyolysis generally no drug interactions got to be a little careful with some cyclosporine or some fibroids or drugs like tripe or became generically available in december 2016 no other copycat
Drugs but in 2016 just to tell you how big a salad this is zetia had sales of two and a half billion dollars in vytorin sales in excess of a billion dollars now in 2017 the sales were around two billion dollars the sales are off since 2011 but they’ve increased the price of the drug they keep increasing the price of the drug even though they haven’t done anything
Different with the drug same chemical they discovered long time ago brought to market a long time ago they just keep increasing the price so if you want the generic version and you want to pay cash and you go over to albert’s and say for your vaughan’s it’s gonna be 300 bucks on the other hand if you go over and you want to pay cash and you stopped off at costco the
Drug would be $42 walmart walgreens cvs 60 to 80 dollars so you go figure out why there’s such a big difference in the price the cash price if you have a coupon it’s 13 to 15 dollars now as an example of what they’ve done in the price if you look at the fourth quarter in 2009 the drug was selling the name-brand was selling for three dollars and twenty three cents
A pill the price increased to the fourth quarter in 2015 to seven dollars and 88 cents a pill if you buy the brand-name you buy the zetia instead of the generic form cash price is going to be $438 with coupon it’s going to be $360 and if you buy the vytorin that’s the combination of the zetia and the simvastatin well the price on the generic drug is going to be
Somewhere in excess of 225 dollars cash or if you buy the brand name instead the price for that’s going to be about $450 and by the way if you go over to the store you go over to the walmart you can get a month worth of simvastatin that’s the soak or generic soak or 40,000,000 pill you can get that for four dollars and you can buy the generic zeliha if you wanted
On prescription for less than $15 so why spend two hundred three hundred four hundred dollars just to take it as a single solitary pill so basically after the drug has flopped they keep trying to resurrect it but the irony now is the drug is off patent so generics are available so i suspect we’re probably going to be bombarded with some advertisements in the near
Future because of the most recent study but from what we’ve discussed dough just doesn’t seem like it ought to have a future if you’d like to know more about cholesterol cholesterol lowering you wouldn’t know more about the zocor the lipitor some of the other medicines what some of the other videos that we have on this channel anyway thanks for watching i’m dr. ken landau you
Transcribed from video
Zetia By wellnowdoctor
