Prevention and treatment of atherosclerosis requires risk factor control, including the treatment of hypertension and diabetes mellitus, and lifestyle modification, i.e. diet, exercise and cessation of smoking. Established therapeutic approaches to atherosclerosis chiefly fall into two categories: lipid-lowering and anti-hypertensive therapies and include a number of drug categories, with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) being the most widely prescribed. The leading brands in the categories discussed are Lipitor, Plavix, Norvasc, Crestor. Zetia and Zocor1.
|Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, which is involved in cholesterol synthesis, especially in the liver. In the short term, they decrease cholesterol and LDL, but over time this rises to baseline levels, However in long-term therapy, LDL levels remain low, which is believed to be due to an increase in the number of LDL receptors. Receptor density is an important factor in atherosclerosis, patients with familial hypercholesteremia may have less than half the normal level of LDL receptors, and statin therapy has proved effective in such cases2.
The effect of statins may extend beyond the regulation of lipid content. These actions, which include modification of endothelial function, plaque stability, and inflammatory pathways, are widely referred to as 'pleiotropic effects', and indicate that the therapeutic potential of statins might extend to other inflammatory disorders or conditions such as transplantation, multiple sclerosis, rheumatoid arthritis and chronic kidney disease3. Known actions include the following:
Specifications for their use are as follows and are summarised in table 1:
Other effects include headache (<5%), elevation of liver enzymes (1-2% patients), hepatitis rarely, gastro-intestinal effects including abdominal pain, flatulence, diarrhoea, nausea and vomiting (<5%). Rash and hypersensitivity reactions including angiodema and anaphylaxis are rare. It is generally considered that side effects are rare and far outweighed by the benefits12. Rosuvastatin and atorvastain are the most potent statins in terms of lowering LDL, followed by simvastatin and pravastatin. Differences in increasing HDL or decreasing triglycerides are less clear.