In our body, cholesterol goes through circulation with the aid of lipoprotein (transporter protein for lipids in blood circulation). There are some kinds of lipoprotein, with the main kinds are LDL (low-density lipoprotein) and HDL (high -density lipoprotein). LDL is needed to take cholesterol from liver to peripheral tissue and vessels. If LDL exists in high level, atheroma could be formed. Reversely, HDL takes cholesterol from peripheral tissue back to the liver.
Previous consideration is that high level of HDL is only "good" when LDL is low. But then this is proved incorrect. LDL is the most important target in dyslipidemia therapy. If your LDL is low enough (below 70 mg/dL), you may not "need" high HDL. But if your LDL is moderately low (about 100 mg/dL or higher but not exceed 130-160 mg/dL), high LDL may be more beneficial.
Hypolipidemic medicines are useful in many kinds of dyslipidemia, to lower LDL level or to lower triglyceride level. Some medicines are used to produce more HDL, but most of them are still in development. Main medicines for dyslipidemia are statins, fibrates, resins, niacin, and some other medicines.
1. Statins (HMG-coA reductase)
This group of medicine inhibit HMG-coA reductase enzyme, which is the most important enzyme in first step of cholesterol formation. Lovastatin, pravastatin, and simvastatin have reversible inhibition effect; while atorvastatin and rosuvastatin have more irreversible effect. There are several statins in market: lovastatin, simvastatin, fluvastatin, pravastatin, atorvastatin, and rosuvastatin. Several statins are in development; such as pitavastatin. Others have been withdrawn from market, like cerivastatin.
Statin has wide clinical indications. Besides lowering LDL in dyslipidemia with high LDL level, secondary statin can lower risk of cardiovascular diseases and complications in patients with history of cardiovascular problem. Statin has several adverse effects, such as muscular problem and hepatotoxicity in some individuals.
Statin is preferably be given in the evening, to prevent rising of cholesterol level in the morning. About statin, we will discuss in separated article.
2. Fibrates
Fibrates work to enhance the effect of lipoprotein lipase enzyme, lower the production of VLDL, and enhance the uptake of LDL by liver. Some fibrates in market: fenofibrate, ciprofibrate, clofibrate, gemfibrozil, and bezafibrat.
Clinically, fibrates are more indicated to lower triglycerides, with or without high cholesterol level. Fenofibrate also has uricosuric effect, thus it is suitable for dyslipidemic patients with hyperuricemia.
Since fibrates also causes muscular problem like statin, these medicines should not be combined if it is not very necessary since the risk of rhabdomyolisis would be higher. Gallstone risk is higher with clofibrate.
3. Resin
Resins bind bile acids which are produced by gallbladder, thus bile acid reuptake from portal vein will be lowered.
Resins in market: cholestyramine, cholestipol, and colesevelam.
Colesevelam is somewhat different from other resins, due to its form (tablet, not sachet, thus this is more convenient for patients); and its effectivity against diabetes.
Other adverse effects are gastrointestinal symptoms, pruritus, rashes, and muscular pain. This medicine should not be given in alcoholic dyslipidemic patients.
4. Niacin
Niacin, or nicotinic acid, or vitamin B3; is the best "medicine" to enhance HDL concentration than other hypolipidemic agents. Unfortunately this medicine has flushing and palpitation adverse effects, which are often intolerable. Then niacin is combined with laropiprant (in experiment) to lower this adverse effect incidence. Very high dose can cause liver function impairment, uric acid impairment, and blood glucose impairment.
5. Ezetimibe
Ezetimibe is an azetidinone cholesterol absorption inhibitor, it inhibits absorption of cholesterol from duodenum. Based on its mechanism of action, ezetimibe sometimes is classified in one functional class with resin.
This medicine is usually given together with statin, especially for patients who do not optimally respond to monotherapy of statin.
Ezetimibe has been proven inferior against extended-release niacin in regressing carotid intima-media thickness; when combined with statin. [read here] This trial had made ezetimibe not very popular for a while.
6. Others
Anacetrapib and torcetrapib: both are cholesteryl-ester transfer protein (CETP) inhibitors. By this mechanism, HDL cholesterol should be higher.
But clinically, torcetrapib failed in preliminary clinical study due to hypertensive complications. Combined with JUPITER trial results; it is now strongly suggested that too-high HDL level is not always beneficial for cardiovascular health. Anacetrapib, so far does not cause hypertension, but long-term safety data is yet to be known.
Fish oil: It is a good source of omega-3 fatty acids which is beneficial to lower triglycerides, but it also makes cholesterol higher. Triglyceride is more associated with ischemic heart disease. This supplementation is only given in several countries; for pure hypertriglyceridemia.
Probucol: this medicine's effect is also to enhance HDL production, but since its cardiovascular effect (proarrhythmic effect) was found prominent; this medicine has been abandoned then.
Consideration of choosing pharmacotherapy
- High LDL, normal-high triglyceride: Statin
- High LDL, normal triglyceride: Statin
- Normal-high LDL, high triglyceride: Fibrat
- Normal LDL, high triglyceride: Fibrat
- Normal LDL, low HDL, normal triglyceride: consider changing lifestyle first, if failed, give niacin.
- High LDL, low HDL, normal triglyceride: Statin
Need more information? Check our Download section to see how these medicines work.
References:
Rang and Dale's Pharmacology, 7th ed; 2011; 285-292
Taylor AJ et al. N Engl J Med 2009; 361: 2113-2122
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