Comparison of cholesterol drugs
The following table contains an overview of cholesterol drugs, together with a rating of their effectiveness, agreeability and safety:
| Active ingredient class | Example drugs | Effects | Efficacy | Agree-able-ness* | Safety* |
| Statins | Lipitor®, Zocor®, Crestor®, Lescol®, Mevacor®, Altocor®, Pravachol®, Selektine®, Vytorin® | Lowers: • LDL-C by 30-50% • Triglycerides by 20-40% Raises: | ***** | **** | **** |
| Fibrates ("fibric acids") | Bezalip®, TriCor®, Lopid® | Lowers: • LDL-C by 10% • Triglycerides by 40-60% Raises: | **** | *** | *** |
| Ezetimibe | Zetia® | Lowers: • LDL-C by 20% | *** | **** | **** |
| Nicotinic acid | Niaspan® | Lowers: • LDL-C by 0-15% • Triglycerides by 30-50% Raises: | *** | ** | *** |
| Bile acid sequestrants ("resins") | Questran®, Welchol®, Cholestagel®, Colestid® | Lowers: • LDL-C by 20% Raises: | *** | * | **** |
Scale: * (poor) to ***** (excellent)
*Agreeableness = frequency of uncomfortable, but harmless side effects
*Safety = overall severity and frequency of side effects
If a change consisting of diet and regular exercise does not sufficiently lower your cholesterol level, your doctor will prescribe cholesterol-lowering drugs. The specific drug prescribed will depend on the kind of blood lipid (LDL cholesterol or triglycerides) to be lowered.
Statins: Blocking The Synthesis Of Cholesterol In The Liver
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Statins are a relatively new class of cholesterol lowering drugs; the first statin was approved by the FDA 20 years ago in 1987. Statins work by inhibiting the enzyme responsible for generating cholesterol in the liver. The process is called HMG-CoA-reductase which is why statins are also called HMG-CoA-reductase inhibitors. To satisfy any cholesterol needs that can no longer be met by synthesis alone, the liver absorbs cholesterol from the blood which drops the level of serum LDL cholesterol.
Statins can lower LDL cholesterol by 30 to 50% when taken in standard doses. For a comparison of the LDL-lowering capacity of different statins, please visit here.
Statins are considered to be relatively safe. Muscle problems and gastrointestinal symptoms such as flatulence, congestion or nausea are some of the more common side effects, although they are not frequent. A rare (normally less than 1 in 10,000 patients) but serious side effect is rhabdomyolysis which causes parts of the muscles (the rhabdomers) to disintegrate. When this muscle debris begins to damage the kidneys, kidney failure may result.
The drug Baycol® (Lipobay®) containing cerivastatin had to be withdrawn from the market in 2001, because rhabdomyolysis occured approximately 10 times more often than with other statins. Care must be taken if statins are combined with other cholesterol lowering drugs such as nicotinic acid and fibrates in particular. The danger of rhabdomyolysis increases if statins and fibrates or nicotinic acid are taken together.
Prominent drugs containing statins include Lipitor® and Zocor®, the world's best selling and fifth best selling drug in 2005, respectively.
Fibrates (Fibric Acids)
Fibrates are an older drug class than statins and have been used since 1967. Their main function is to lower serum triglycerides by approximately 40 to 60%. LDL cholesterol may be lowered slightly by up to 10%, and HDL cholesterol or the "good" cholesterol may rise by approximately 10 to 20%.Fibrates are believed to influence the metabolism of triglycerides and cholesterol by targeting special receptors in the liver. As a side effect, fibrates change the composition of bile which increases the risk of gallstones. Nausea, sickness, diarrhea and other gastrointestinal discomfort is relatively common, especially in the beginning of fibrate therapy. As for statins, rhabdomyolysis or the breakdown of muscle tissue may occur which can cause severe kidney problems. Care must be taken when combining fibrates with statins because of an increased risk of rhabdomyolysis. If fibrates are to be combined with statins, gemfibrozil seems to cause fewer side effects.
Clofibrate, the first fibrate on the market, often causes pronounced side effects such as the risk of gallstones. Consequently, most countries have withdrawn it from the market, withdrawn, together with related fibrates such as etofibrate. Newer fibrates such as bezafibrate (Bezalip®), fenofibrate (TriCor®) and particularly gemfibrozil (Lopid®) are considered much safer.
Ezetimibe: Inhibiting The Uptake Of Cholesterol In The Gut
Another method to reduce blood cholesterol levels is to inhibit its uptake in the gut. This is how ezetimibe, the active agent in the drug Zetia® marketed by Merck and Schering-Plough works.
You can expect your LDL cholesterol to be reduced by approximately 20%. Because Ezetimibe is a relatively new agent, data on possible side effects is not as readily available as for statins or fibrates. Headaches and diarrhea are relatively common, and muscle aches have also been recorded, although rare. One main advantage for ezetimibe is the fact that it can be combined with other cholesterol-lowering drugs. For example, in 2006, the FDA approved a combination containing a fibrate (fenobibrate/TriCor®) in cases where both cholesterol and triglycerides were elevated called "mixed hyperlipidaemia." Ezetimibe can also be combined with statins to increase the LDL cholesterol lowering effect.
Nicotinic Acid: Increasing The Good Cholesterol
Nicotinic acid (Niacin) is another name for vitamin B3. When taken in very high doses (grams), it reduces triglycerides and increases HDL or "good" cholesterol by approximately 35% and 15 to 30%, repectively. LDL cholesterol may be lowered slightly.
Nicotinic acid is not considered an effective treatment of high triglyceride levels because of its side effects. One very frequent side effect encountered early in nicotinic acid therapy (by as many as 50% or more of patients) is "flushing" or a facial reddening and a feeling of heat, sometimes accompanied by itching. Although this may be a transient problem occuring only during the first weeks of therapy and can be controlled by taking aspirin or iboprofen, many patients consider it unacceptable. The worsening of diabetes by elevatin blood sugar levels, liver damage or gout are other potential risks.
Bile Acid Sequestrants ("Resins"): Removing Bile Acids To Deplete Cholesterol Supply
As the name suggests, bile acid sequestrants or "resins" bind bile acids. Instead of being recycled by re-uptake in the lower area of the gut, bile acids bound to sequestrants are excreted in stools. As a result, the supply of cholesterol (the raw material for bile acid) is depleted as new bile acid must be manufactured in the liver.
With bile acid sequestrants, LDL cholesterol levels can be reduced by approximately 20%. Bile acid sequestrants are not absorbed into the bloodstream, but are confined to the digestive system until excreted in stools. That's why they are considered to be especially safe without any serious side effects. Although they can interfere with the absorption of several drugs and fat-soluble vitamins such as Vitamin A, D, E and K, individuals can control this by taking other drugs several hours earlier or later and by supplementing the aforementioned vitamins.
However, patients' "compliance" (the regular, long-term intake of the drug) of bile acid seuqestrants is usually low since it can cause severe intestinal discomfort, diarrhea and sickness. In addition, several grams of sandy-textured resin must be taken daily, which adds to the high drop-out rate of patients on sequestrant therapy. An advantage of bile acid sequestrants is the fact they can be combined with other forms of cholesterol or triglyceride-lowering therapies.
A Promising New Approach: CETP Inhibitors
One of the most exiting new developments to treat lipid disorders are cholesteryl ester transfer protein (CETP) inhibitors. CETP inhibitors are not currently available on the market. However, several large pharmaceutical companies are working on this new drug class, including Pfizer (drug: torcetrapib), Merck (drug: anacetrapib), and Roche (drug code: R-1658).
CEPTs are liver enzymes that transfer cholesterol from HDL to LDL particles, turning "good" cholesterol into "bad" cholesterol. The primary effect of suppressing CEPTs is a significantly increased serum HDL cholesterol level. The lowering of bad LDL cholesterol is a positive side effect.
This approach has been criticized recently when Pfizer's torcetrapib failed to lower heart problems in a recent clinical trial. As an unforeseen side effect, it actuallyl raised blood pressure, thereby increasing heart problems and the overall risk of death. Although Merck pointed out that their CETP candidate anacetrapib did not increase blood pressure and Roche claimed their product's development was "on track," it is not known whether CETP inhibitors can fulfill their promise of becoming a standard treatment for patients with heart disease, as predicted only a year ago.
Special Case: Apheresis - A Non-Drug Intervention To Lower Cholesterol
Apheresis is similar to blood dialysis for patients with serious kidney damage: their blood is pumped through a machine that filters out LDL cholesterol before returning it to the patient. This method for lowering cholesterol is usually confined to severe cases that fail to respond sufficiently to drug treatment for lowering cholesterol.
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