Monday, June 22, 2020

Lowering cholesterol? How, why?

This post was suggested by a reader, who had read enough about the coronavirus, and it is a topic that merits attention. Cardiovascular disease remains by far the number one killer in the developed world and is rapidly rising to that spot in the developing world as well, and our ability to prevent heart attacks is in large part related to lowering cholesterol.

The first point to note is that cholesterol is not arsenic – cholesterol is part of normal cells, and no one dies of cholesterol. It has, however, been known for many decades that an elevated level of cholesterol, along with high blood pressure and smoking, increases the risk of developing coronary disease. Norwegian researchers in 1939 described families with abnormally high levels of blood cholesterol and premature heart attacks. This led, beginning in the 1950s, to attempts to lower cholesterol with diet and medication. Most of the medications which were then available, which included nicotinic acid, fibrates and cholestyramine, were not very effective and/or were difficult for people to take for any time, and their use did not reduce the risk of heart attack by a large amount.

A breakthrough in cardiology occurred with the development of the class of drugs technically known as HMG-CoA reductase inhibitors and widely known as “statins.” The first in this class, lovastatin, was discovered in 1978 and first tested in humans in 1980. Multiple similar drugs followed, and we now have seven on the American market. They vary in potency, but all work in a very similar way. The first major trial of using a statin to prevent CV death was conducted in the west of Scotland, among men at high risk of heart attack. Participants were enrolled between 1989 and 1991 and the results of the trial were published in 1995. Those taking the active drug, which in this trial was pravastatin, had about 31% fewer heart attacks, and there was about a 9% reduction in total mortality (from 38.6% to 34.7%) over an extended 20-year follow-up. Multiple later trials, done in lower risk patients, all showed similar results: fewer heart attacks and a trend to lower overall deaths in statin-treated groups.

I do not own stock in any healthcare companies, so have no conflict of interest in stating that the statins as a class are one of the best medicines in our armamentarium. Most are now available generically and are dirt-cheap in the big picture of pharmaceutical products; they are well-tolerated by most people; and have very few bad side effects. There was a flurry of concern a few years back about them contributing to dementia, but this has been disproven by many large studies. They do seem to slightly hasten the onset of diabetes in people prone to it, but the benefit far outweighs the risk.

There is one fly in the ointment: many people develop muscle aches from taking a statin. Only a tiny number have muscle damage (which can be measured with a blood test), and in my opinion if you fall in that tiny number you should never take any statin, but 5-10% complain of muscle aching that goes away when you stop the drug. In some cases, taking a different statin can be done without the problem recurring, but some get the same reaction to every statin they try. What options are available if you are in this group?

The first step is to decide with your doctor if you truly need to have your cholesterol lowered. While statins seem to have a similar relative reduction in heart attack risk in all groups, there is a difference between relative and absolute risk. Let’s say that taking a moderate dose of a statin reduces your risk of having a heart attack in the next 10 years by 25%. If that risk is 40%, then reducing it by 25% means you have reduced your odds by 10%. If that risk is 4%, reducing it by 25% means your actual benefit is a 1% risk reduction – perhaps not worth it in your mind. There are on-line risk calculators that will help you calculate your personal risk.

If you feel that lowering your cholesterol is important and cannot take a statin, there are several choices available, but NONE of them has been studied for risk reduction when taken alone – all have been shown to lower your risk of heart attack when added to a maximally-tolerated dose of a statin.

Ezetimibe (Zetia) inhibits absorption of cholesterol from the intestine and reduces cholesterol by about 18% (compared to 25-60% reduction with a statin). There are two new injectable drugs, called PCSK9 inhibitors, that are very potent, but are extremely expensive and require self-injection every 2-4 weeks. Unless you have a very high risk, your health insurance company is likely to balk at paying for these. The newest entry is bempedoic acid (Nexletol), which also lowers cholesterol by about 18%, and it has also only been tested as an add-on.

Finally, do not forget lifestyle changes: a better diet, weight loss, moderate aerobic exercise. If you are a smoker, quitting will do more to reduce your heart attack risk than any pill.

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