Gettysburg Medical News
The Clinical View
by P.E. Hoffsten, MD
19 March 2008

 A DIFFERENT WAY TO TREAT CHOLESTEROL

            In the 1950’s, medical science hadn’t worked out an easy way to measure blood cholesterol.  But in research laboratories, it was recognized that the heart attack epidemic in the United States had something to do with high blood cholesterol.  Soon we learned that there was good cholesterol (HDL, high density lipoprotein) and bad cholesterol (LDL, low density, lipoprotein).  It turned out that a high blood HDL was associated with longevity where as a high blood LDL was associated with an increased incidence of heart attack, stroke and premature death.  Thus, the target became how to get the LDL to go down or the HDL to go up. 

            Making the HDL go up has not really been achieved medically.  We have found that all of the cholesterol drugs may raise HDL slightly but none seem to do it in a meaningful way.  The three ways to get a high HDL include picking the right parents, two alcoholic beverages a day, or running marathons.  Only the two alcoholic beverages per day are easy and some people struggle with that in either direction. 

            By the 1970’s, we had worked out that on the average a person eats about 300 milligrams a day of cholesterol.  The American Heart Association touted and pushed low cholesterol diets which everyone soon learned didn’t work worth a hoot.  By the time you get the cholesterol in your diet down to 250 milligrams a day, your diet tastes like cardboard and nobody will eat that for long.  Thus, dietary control of cholesterol was a huge flop.

            But it was also learned that the body makes about 1200 milligrams of cholesterol per day or about 80% of what we are exposed to each day.  If there could be a big dent made in the amount of cholesterol made, perhaps a lower blood cholesterol could be achieved.  It was then learned that a wonderful enzyme (machine) in our bodies called 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HGM coenzyme reductase) was the pivotal step in making cholesterol.  It was reasoned that if that enzyme could be blocked, the amount of cholesterol we make each day could be significantly reduced.  The first drug on the market that could do this was called Mevacor (lovastatin) which is now generic.  There followed Zocor (simvastatin), Pravachol (pravastatin), Lipitor (atorvastatin), Crestor (rosuvastatin), Lescol, and Baycol.  Baycol was a very good drug but was taken off the market because of a drug interaction problem.  This family of medications is called the statins and they are clearly the most effective cholesterol lowering agent medical science has ever found.

            Unfortunately, all of these drugs carry two relatively bothersome side effects.  In some people, they cause muscle aches.  In another group, they cause liver abnormalities that can lead to significant liver damage.  The estimates are that 3-5% of the general population has this type of problem. 

            The reason that some people seem to have problems has to do with individual variation in the rate at which the body eliminates these drugs.  Some people eliminate the drugs daily.  Others may take 4-9 days to eliminate the drugs.  Thus with such a huge variation in the rate at which a person eliminates the drugs, you would think that the doses would have to be equally variable.  Thus, some people take only 10 milligrams a day of a medication while other individuals may take as much as 80 milligrams of the same medication.  But even the 10 milligram a day dose is way too much for some people.

            Thus, in the past few years, doctors have experimented with using the drugs at 10 mg every other day or every three days or in some cases even once a week.  Success with these regimens has been mixed.  For some people, decreasing the dose down to 2 or 3 times a week is successful in avoiding side effects and lowering the cholesterol but for some people even these alternate programs don’t work.

            This past week an article appeared in the American Journal of Cardiology that suggested using a combination of ezetimibe (Zetia) and then using one of the statin drugs just twice a week.  When this was done, 51 of 56 patients tested were successful in lowering their LDL cholesterol by an average of 56 milligrams% without intolerable side effects.  On average, this amounted to a drop in the LDL cholesterol from 150 milligrams% down to 94 milligram %.  This would have a huge effect on the risks of heart attack or stroke.  Unfortunately, ezetimibe is still under patent and somewhat expensive but simvastatin and lovastatin are now both generic and can be obtained for $4.00 a month at some pharmacies.

            For those who have struggled with cholesterol control and found statin side effects intolerable when used daily, this program of using ezetimibe to eliminate cholesterol into the stool along with a tiny dose of statin drug to prevent resynthesis of cholesterol seems to work remarkably well in 5 out of 6 people who tried it. 

This and other columns available at www.macpierre.com.