For nearly thirty years have been the mainstay of treatment for high cholesterol and cardiovascular disease. For some people, however, they simply do not work. For people who do not respond to statins, two new drugs may be what the doctor ordered.
There seems to be no end to how low doctors want cholesterol levels to go.
Fifty years ago, high cholesterol was not treated unless total cholesterol levels ran over 300 mg/dl (7.8 mmol/l). Thirty years ago, a total cholesterol level of 200 mg/dl (5.2 mmol/l) was thought to merit treatment, and currently, many people who have a history of heart disease or diabetes are put on statin medications when their LDL cholesterol levels are as low as 100 mg/dl (2.6 mmol/l). Some people, however, suffer truly life-threateningly high cholesterol levels no matter how they diet or whether or not they take statin medications. For them, there have been very few alternatives until extremely recently, although not everyone will benefit from the new medications, either.
Statins Work Well In Most Cases
Most of us have been conditioned to think of high cholesterol as a condition that is caused by consuming too many foods that contain cholesterol, but that is not really the case. The liver makes about 85 percent of the body's total cholesterol from fats and carbohydrates. Since most of the body's cholesterol doesn't come from food, a low-cholesterol diet will make at most about 15 percent difference in bloodstream cholesterol levels, and often not even that much.
However, a class of compounds known as the statins have become a mainstay of medical therapy for cholesterol problems over the last 30 years. These medications, which include Altocor and Mevacor (lovastatin), CRESTOR (rosuvastatin), Lescol (fluvastatin) Lipitor (atorvastatin), Livalo (pitavastatin), and Zoco (simvastatin), among others, have entered the ranks of the best-selling medications of all times. They are so popular that some doctors have even been proposed that they be added to drinking water, like fluoride.
Statin drugs interfere with the action of an enzyme called HMG-Co A reductase. This enzyme is necessary for the production of cholesterol by the liver. Blocking this enzyme makes it possible to lower cholesterol by more than the 10 to 15 percent possible with diet and some earlier cholesterol drugs. That is not all statin drugs can do. They block inflammation. This keeps arteries from narrowing so that they are blocked by cholesterol-laden plaques or clots. The statin drugs help existing cholesterol plaques stabilize, so that they do not rupture and trigger a heart attack. They stimulate the liver to take LDL cholesterol out of the bloodstream.
They stop a process called prenylation, which makes certain proteins "water-phobic," so they would cause irritation in the bloodstream.
Not Everyone Benefits From Statins
Although statin medications have a number of proven beneficial effects, not everyone benefits from them. A substantial number of people suffer intolerable side effects from statin medications. In a small number of people, statins cause a phenomenon known as rhabodmyolysis. Muscle tissue breaks down. This hurts. It also releases byproducts that are toxic to the kidneys.
In some people, statins cause memory loss. This is particularly a problem with the more potent statins, such as CRESTOR. Statins may increase the anticoagulant effect of warfarin (Coumadin). They possibly increase the risk of diabetes and certain kinds of cancer. The major drawback of statin therapy, however, is that they do not work for the people who most urgently need lower cholesterol, those who have familial hypercholesterolemia.
An Entirely New Way to Treat High Cholesterol
People who have familial, or hereditary, hypercholesterolemia, or high cholesterol, have one or two copies of a gene that changes the way the liver responds to LDL cholesterol. In people who do not have these genes, the liver takes LDL out of the bloodstream and transforms it into HDL cholesterol. LDL is usually termed "bad cholesterol," but the truth is that everything about LDL is not detrimental to health. LDL cholesterol is a fuel for the white blood cells that fight bacterial infection. It does not necessarily clog arteries. Only smaller, spent particles of LDL cause atherosclerosis.
If LDL is never taken out of the bloodstream, however, it collides with sugar and other oxidizing compounds, such as those containing iron and copper, and forms a foamy plaque on the linings of arteries. These plaques can harden and cause "hardening" of the arteries. In people who have familial hypercholesterolemia, hardening the arteries can occur before the age of ten, and most people who have two copies of the gene that causes the condition die before they age of 30. Statin drugs can slow down the production of cholesterol, but the liver is either completely unable (if there are two copies of the gene, from both parents) or largely unable (if there is only one copy of the gene, from one parent) to regulate LDL.
Two new drugs have received preliminary approval in the United States to treat high cholesterol that cannot be addressed with statins. One of these drugs is Praluet, which has the generic name of alirocumab. It was discovered by Regeneron Pharmaceuticals and is being developed with the help of pharmaceutical giant Sanofi. It received preliminary approval by the US FDA on June 8, 2015. The other of these drugs is evolocumab, or AMG-145, made by Amgen. It received preliminary approval by the FDA on June 10, 2015.
These drugs do something entirely different to lower cholesterol.
They block a different enzyme, known as proprotein convertase subtiolin/kexin type 9, or PCSK9. This enzyme ordinarily ensures that the liver does not take too much LDL out of the bloodstream. When a receptor site grabs an LDL molecule out of the bloodstream, it ordinarily shuts down permanently, due to the action of PCSK9. These new medications, which are actually cloned antibodies, keep PCSK9 from latching on to the receptor site so it can be used over and over again to take LDL out of the bloodstream and into the liver where it is transformed into the "good" cholesterol, HDL.
There are some people who may benefit a great deal from these new drugs. People who cannot tolerate statins due to side effects probably will benefit from the new drugs. Clinical trials show about a 50 percent reduction in total cholesterol and LDL, to relatively healthy cholesterol levels, after using the drugs for just a few months.
The only familial hypercholesterolemia patients who will benefit from the new drugs are those who have only one copy of the gene that causes the disease. They have some LDL receptors, and the drugs will help preserve them. People who have two copies of the genes for familial hypercholesterolemia, however, have no LDL receptors to be preserved, and will not respond to the new drugs.
Assuming the FDA listens to its scientists, one or both of these drugs should be on the market in late 2015. Expected cost in the United States is $600 to $1000 per month.
Sources & Links
- Micheal O'Riordan.Big LDL Drops With PCSK9 Inhibition in Grouped Phase 2 Studies. Medscape Medical News. 12 September 2013.' Liz Szabo. New cholesterol-lowering drugs hold promise, at a huge projected price tag. USA Today. 8 June 2015.
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