Lipid-lowering drugs

Lipid-lowering drugs

There are several classes of established lipid-lowering, or antihyperlipidemic drugs available to the prescriber.

The choice of which agent to use depends greatly on the patient's cholesterol profile, cardiovascular, liver and kidney function.

Statins are designed to lower LDL, the 'bad cholesterol' most strongly linked to vascular disease. Notable side-effects include myopathy and rhabdomyolysis. Some evidence suggests that statins should not be used in patients older than 75 who have no history of heart disease or stroke. Statins inhibit the enzyme hydroxymethylglutaryl-CoA reductase (HMGCR). Examples of approved statins include atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin.

Fibrates are prescribed to reduce hypercholesterolemia in patients intolerant of or unsuitable for statin therapy. Fibrates increase HDL ('good cholesterol') and lower triglyceride levels. The fibrate-induced reduction in insulin resistance is useful when the dyslipidemia is associated with other indicators of the metabolic syndrome (e.g. hypertension and type 2 diabetes mellitus). Fibrate therapy is unsuitable for patients with low HDL levels, and treatment should be withdrawn if HDL-C levels are severly depressed soon after initiation. Fibrates are recommended as first line therapy only in patients with very high triglyceride levels. Fibrates activate peroxisome proliferator-activated receptors (PPARs), especially PPARα. They are metabolised by cytochrome P450 3A4 (CYP3A4). Examples of approved fibrates include bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil.

Niacin (nicotinic acid or vitamin B3) is used as a vitamin supplement. It lowers both cholesterol and triglyceride concentrations by inhibiting synthesis; it also increases HDL cholesterol. Used as an adjunct to statin therapy, or alone if statins are not tolerated. Not to be used if the patient has a history of peptic ulcer disease or arterial bleeding. The nicotinic acid derivative acipimox can be used in similar situations. Inositol nicotinate can be used for peripheral vascular disease, but not in patients in the acute phase of a cerebrovascular accident or who have suffered recent myocardial infarction. NICE does not recommend the use of inositol nicotinate to treat intermittent claudication in patients with peripheral arterial disease.

Bile acid sequestrants are synthetic polymeric resins which prevent reabsorption of bile constituents from the gut, thereby acting a hypolipidemic agents. Also used for other purposes such as the treatment of chronic diarrhea due to bile acid malabsorption and for the prevention of pruritus in patients with chronic liver disease. As hypolipidemic agents these are less effective than statins. Not to be used when blood triglyceride levels are elevated. Examples include cholestyramine, colestipol and colesevelam.

Ezetimibe inhibits the intestinal cholesterol uptake protein Niemann-Pick C1-like protein 1, a critical mediator of intestinal cholesterol absorption. Has only a modest effect as a mono-therapy, but can be used adjunctively with dietary measures with or without statins to treat primary hypercholesterolaemia and homozygous familial hypercholesterolaemia. Avid use in patients with moderate and severe hepatic impairment.

Lomitapide inhibits the microsomal triglyceride transfer protein (MTTP) resulting in reduced lipoprotein secretion and circulating concentrations of lipoprotein-borne lipids such as cholesterol and triglycerides. Only to be used under expert supervision in patients with homozygous familial hypercholesterolaemia, as an adjunct to dietary measures and other lipid-regulating drugs. Since lomitapide can interfere with the absorption of fat-soluble nutrients, vitamin E and fatty acids supplements are essential.

Phytosterols (plant sterols and stanols) are naturally occurring steroid-like compounds similar to cholesterol. Stanols are saturated sterols, having no double bonds in the sterol ring structure. Despite being effective in lowering LDL cholesterol, the benefits of phytosterol-enriched foods and dietary supplements in cardiovascular disease and overall mortality are yet to be proven [Genser et al. (2012)]. The most commonly occurring phytosterols in the human diet are β-sitosterol, campesterol and stigmasterol; the most common stanols are sitostanol and campestanol.

Orlistat inhibits pancreatic lipase, thereby reducing absorption of fats from the diet. Used as an adjunct to a reduced-calorie diet as an anti-obesity therapy, in obese patients suffering additional risk factors such as type 2 diabetes, hypertension, or hypercholesterolaemia.

Antihyperlipidemic drugs slideset

This a is a slide set (42 slides) covering clinically used drugs for lipid lowering. This is an updated version of the lecture series for the 2021-2022 academic year. It is suitable for intermediate level learners.

Contributed by Dr. Zoltan Varga, Semmelweis University (Hungary)

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