Lipid-lowering drugs

Hyperlipidaemias, multifactorial conditions partly genetically and partly life habit induced, are the most important underlying risk factors for cardiovascular disease. They can lead to arterial lipid deposition with a consequent increased risk of coronary events. The primary effort in hypolipidaemic drug therapy is focused on the lowering of the primary carriers of cholesterol, the low-density lipoproteins (LDLs), but more recent efforts have been placed on the lowering of triglycerides. Reduced levels of the protective highdensity lipoproteins (HDLs) are generally considered a primary risk factor, but ‘dysfunctional’ HDL may probably be a more important factor. Among drugs primarily reducing LDL cholesterol the most important systemic agents are statins. Non-systemic agents, such as resins, have a lesser use, whereas ezetimibe is frequently given in combination with statins. A new series of systemic compounds, the inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), recently available, have a higher activity on LDL cholesterol. Drugs indicated for the treatment of the homozygous forms of hypercholesterolaemia are lomitapide, an inhibitor of the microsomal transfer protein, and the antisense nucleotide mipomersen, designed to inhibit synthesis of apolipoprotein B. Treatment of hypertriglyceridaemias mainly relies on fibrates, activating the peroxisomal proliferator-activated receptor-α. They treat particularly the atherogenic dyslipidaemias (elevated triglycerides with low HDL cholesterol). Nicotinic acid is less frequently used and the omega-3 fatty acids have an as yet unclear cardiovascular protective activity.