Cardiovascular disease Statins

Background It is well known that hypercholesterolemia is a major risk factor in the progression of atherosclerosis, the major cause of cardiovascular diseases. Statins are widely used to treat hypercholesterolemia. The mechanism of action of these drugs is to reduce the endogenous production of cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase. Atorvastatin (ATV, Lipitor) is one of the top-selling prescribed oral medications. The only known adverse effect is skeletal muscle toxicity (myopathy) that may be related to the formation of the lactone of the acidic side chain on the molecule. 

The recent years have seen the success of statins like Lipitor (atorvastatin) as hypolipidemic agents that help treating cardiovascular disease primarily by lowering low-density lipoproteins ( bad cholesterol ) levels. Another novel strategy is to tackle the same problem by elevating high-density lipoproteins (H D L or good cholesterol ) levels via inhibition of cholesteryl ester transfer protein (CETP). 

These studies demonstrate that optimal doses of statins reduce the incidence of clinical events in patients with established coronary artery disease, in patients with elevated plasma LDL levels but without existing coronary artery disease, in individuals with normal plasma LDL levels without existing coronary artery disease, and in diabetics, a patient population at high risk of cardiovascular disease. ... 

Hypercholesterolaemia and hypertriglyceridaemia commonly occur in patients with severe proteinuria. It may be associated with a higher incidence of cardiovascular disease. Dietary treatment is of limited value if the underlying cause of the nephrotic syndrome is not successfully controlled. Statins should be considered to lower the serum cholesterol. 

The results of several large clinical trials using the statin drugs (discussed later) show that the tested drugs decreased the risk of both primary and secondary cardiovascular events. The incidence of myocardial infarction and death from cardiovascular disease was reduced in patients with hypercholesterolemia who never had a... 

Statins are helpful in decreasing morbidity and mortality in people with high cholesterol, as well as individuals who have normal cholesterol but other risk factors for cardiovascular disease.66 It is estimated that these drugs decrease the risk of a major cardiac event by approximately 30 to 35 percent, although the benefits depend on the extent that cholesterol is reduced and the influence of other risk factors.91,95,126 Nonetheless, statins are now regarded as a mainstay in treating cardiovascular disease, and efforts are underway to expand the use of these medications and to explore the... 

Gotto AM. Statins, cardiovascular disease, and drug safety. Am J Cardiol 2006 97 (suppl) 3C-5C. 

Fluvastatin (Fig. 21) is a member of the drug class of statins used to treat hypercholesterolemia and to prevent cardiovascular disease. It is able to decrease ROS, such as hydroxyl radicals and superoxide anions generated by the Fenton reaction, and by the xanthine-xanthine oxidase system. The an-tioxidative effect of fluvastatin was thought to have caused not only the scav-... 

The primary goal of therapy is the control of the hypercholesterolemia and prevention of atherosclerotic cardiovascular disease. Patients with heterozygous FH can usually be successfully treated with medications to lower the LDL cholesterol to acceptable levels (Table 14-2). They are generally responsive to treatment with statins, alone or in combination with other drugs, such as bile acid sequestrants (such as cholestyramine) or cholesterol absorption inhibitors (such as ezetimibe) that act additively to upregulate the expression of the functioning LDL receptor as described in the Biochemical Perspectives section. In a few cases, a more aggressive treatment with LDL apheresis (discussed in this section) may have to be considered in order to reach acceptable LDL cholesterol levels. 

PUFAs suppress HMG-CoA reductase and ACE activities, inhibit platelet aggregation, enhance parasympathetic activity and, thus, enhance heart rate variabihty (and thus, have actions similar to that of fS-blockers), and possess diuretic properties either by themselves and/or by increasing the formation of PGAs and PGEs that have been shown to increase renal blood flow and augment diuresis. These actions of PUFAs are similar to that of the polypill that is a combination of aspirin, fS-blockers, statins, and ACE inhibitors, which is expected to reduce cardiovascular diseases by over 70-80% (92). This suggests that PUFAs could function as an endogenous polypill the evidence for this is detailed below. 

Rauch U, Osende JI, Chesebro JH, Fuster V, Vorchheimer DA, Harris K, Harris P, Sandler DA, Fallon JT, Jayaraman S, Badimon JJ (2000) Statins and cardiovascular diseases The multiple effects of lipidlowering therapy by statins. Atherosclerosis 153 181-189. 

HMG-CoA reductase is inhibited by the drug lovastatin, a natural product synthesized by a fungus (Figure 6.14), Lovastatin does not inhibit the enzyme directly it is converted to a compound (similar to the structure of HMG-CoA) that inhibits the enzyme. Ltivastatin, as well as several related compounds in a family of chemicals called statins, have found use in the treatment of cardiovascular disease throughout the world. The study outlined in Figure 6,15 shows the effectiveness of lovastatin in the treatment of cardiovascular disease. The drug lowers... 

Balk EM, Lau J, et al. Effects of statins on nonlipid serum markers associated with cardiovascular disease a systematic review. Ann Intern Med 2003 139 670-82. 

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