HMG Co A Reductase

The more recent use of aggressive medical therapy with beta blockers, ACE-inhibitors, aspirin, and HMG Co A reductase inhibitors has had a profound benefit on those with coronary artery disease and reduced LVEF. To that end, revascularization still plays an important role in mortality reduction. In the Studies of Left Ventricular Dysfunction (SOLVD) database, CABG does improve survival compared to more modern use of medical therapy, with a 25% mortality risk reduction as well as an intriguing 46% risk reduction of sudden death [91]. This benefit improved as LVEF decreased, thus providing evidence that revascularization may stabilize heart function, reduce abnormal remodeling, and thus reduce the propensity to arrhythmogenicity. 

Atorvastatin is an HMG Co-A reductase inhibitor. Pooled data from 21 completed and 23 continuing trials representing 3000 patient-years have shown that constipation, flatulence, dyspepsia, abdominal pain, headache, and myalgia occur in 1-3% of patients. Under 2% of atorvastatin-treated patients discontinued treatment because of an adverse event (1). Serious events in this review amounted to one patient with pancreatitis and one with cholestatic jaundice (1). There were no differences in adverse effects in 177 patients randomized for 52 weeks to either simvastatin or atorvastatin (2). 

Simvastatin is an HMG Co-A reductase inhibitor. Its most serious adverse effect is rhabdomyolysis, which is enhanced by other drugs that inhibit CYP3A4 (1). 

Pravastatin (47) and Mevastatin (48) are anticholesterol drugs which act by competitively inhibiting HMG Co A reductase [75], Pravastatin sodium is produced by two fermentation steps. The first step is the production of compound ML-236B by Penicillium citrinum [75-77], The purified compound was con-... 

Wright R. and Rine J. (1989) Transmission electron microscopy and immunocytochemical studies of yeast analysis of HMG-Co A reductase overproduction by electron microscopy. Met. Cell. Biol. 31, 473-512. 

Atherosclerotic cardiovascular disease HMG co-A reductase inhibitors Lovastatin Pravastatin Simvastatin Primary and secondary prevention of coronary heart disease (CHD) reduced hospitalizations, percutaneous transluminal coronary angioplasties (PTCA), and coronary artery bypass graft surgeries (CABG) reduced all-cause mortality 4S AFCAPS CARE LIPID WOSCOPS >30,000 7,8... 

Another approach to the reduction in blood cholesterol levels has been the development of pravastatin (50) and its congeners as potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A) reductase, the rate-limiting enzyme in cholesterol biosynthesis.52 It has also been discovered that the biological activity of such compounds is dependent largely on the P-hydroxy-8-lactone moiety within the compound.53 This led to the development of more potent compounds, such as NK-104 (51), a congener of pravastatin. 

Mevinolin produced by the fungus Aspergillus tereus, competitively inhibits HMG-Co-A reductase, a key enzyme in the cholesterol biosynthetic pathway, and thereby lowers cholesterol level (Wang and Ng, 1999). 

All of these drugs have the same mode of action. They are HMG co-A reductase inhibitors. Simply stated, they inhibit the liver s production of an enzyme that s essential to the manufacture of cholesterol. These are very powerful drugs, the most potent of which are atorvastatin and rosuvastatin, and are capable of reducing cholesterol, especially LDL, by as much as 50 percent or even more. 

S. M. Grundy, "HMG Co A Reductase Inhibitors Clinical Applications and Therapeutic Potential, " in B. M. Rifkind, Ed., Drug Treatment of Hyperlipidemia, Marcel Dekker, New York, 1991, pp. 139-167. 

HMG Co-A reductase inhibitors (statins) have been shown to reduce the incidence of fatal and non-fatal myocardial infarction, stroke and mortality (all causes), as well as the need for coronary artery bypass surgery. Since no single drug has been shown to be significantly more effective or less expensive than others in the group, none is included in the model list the choice of drug for use in patients at highest risk should be decided at national level. 

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