Pravastatin cholesterol-lowering effects

Recent reports on clinical trials of pravastatin and simvastatin have shown a significant reduction in patient mortality rates for both hypercholesterolemic patients without known coronary heart disease and for those with existing coronary heart disease [7,8], These trials have established cholesterol-lowering agents as an effective treatment for coronary disease and have stimulated the search for new cholesterol-lowering agents with other mechanisms of action. 

In one of our other studies [37], the 6 months therapy with 0,4 mg daily of other HMG-CoA-reductase inhibitor cerivastatin, which is more effective than pravastatin as cholesterol-lowering drug, sharply increased the level of LDL lipohydroperoxides in the blood plasma of patients [37] (Figure 18). At the same time administration of cerivastatin in combination with synthetic antioxidant probucol in daily dose 250 mg did not produce the increase of the LDL lipohydroperoxide level in the plasma during all time of the observation [37] (Figure 18). 

Williams JK, Sukhova GK, Herrington DM, Libby P. 1998. Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys. J. Am. Coll. Cardiol. 31 684-91... 

In 1999, a smdy examined just that — the effects of pohcosanol and pravastatin (a statin drag) on the hpid profile of hypercholesterolemic patients. The researchers demonstrated that pohcosanol was more effective than pravastatin in lowering low-density lipoprotein (LDL), as well as improving the ratios of LDL to HDL and total cholesterol to HDL. As seen in previous studies, pohcosanol also increased HDL. " It is important to note that both drugs in this study were well tolerated with little or no side effects reported. 

Over the last decade, several studies in tens of thousands of patients have revealed that lowering cholesterol, specifically lowering LDL cholesterol with statins, is effective for both primary and secondary prevention of IHD-related events. Statins shown to decrease morbidity and mortality associated with IHD include lovastatin, simvastatin, pravastatin, and atorvas-tatin.22,23 A recent meta-analysis showed that the risk of major adverse cardiac events is reduced by 21% with the use of statins in patients at high risk for IHD-related events.23... 

Endocrine effects Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Small declines in total testosterone with no commensurate elevation in LH have been noted with the use of fluvastatin. Pravastatin showed inconsistent results with regard to possible effects on basal steroid hormone levels atorvastatin, lovastatin, rosuvastatin, and simvastatin did not reduce basal plasma cortisol concentration or basal plasma testosterone concentration or impair adrenal reserve. Appropriately evaluate patients who display clinical evidence of endocrine dysfunction. Exercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels or activity, such as ketoconazole, spironolactone, and cimetidine. 

Other statins include simvastatin (also a lactone prodrug), pravastatin, atorvastatin, and cerivastatin (active form with open ring). The statins are the most important therapeutics for lowering cholesterol levels. Their notable cardiovascular protective effect, however, appears to involve additional actions. 

More controversial is the extent to which primary prevention (treatment of clinically unaffected patients with moderate elevation of cholesterol levels) should include drugs, and whether secondary prevention should ever start with drugs rather than diet. Dietary treatment can lower cholesterol levels in committed subjects, and is obviously less costly than drug treatment. Unforhmately numerous studies have shown that over any substantial period of time (e.g. one year) diet has no clinically significant influence on plasma cholesterol and the wait for diet to have an effect often results in patients being lost from hospital follow-up after their initial myocardial infarction. Evidence comes from the WOSCOPS stud) in which pravastatin 40 mg/day and placebo were compared in 6590 men age 50-70 with LDL cholesterol 4-6 mmol/1 pravastatin reduced coronary heart disease (fatal and nonfatal events) by 31%. The authors estimated that treatment of 1000 such subjects each year would prevent 20 myocardial infarctions. Concerns that primary prevention could have a net adverse outcome (that cholesterol reduction increased the risk of cancer or violent deaths) have been laid to rest by a number of outcome trials. 

The ability of statins to lower hsCRP was first described for pravastatin using data accumulated in the Cholesterol and Recurrent Events (CARE) trial. These data were initially highly controversial because they suggested that statins have both hpid-lowering and antiinflammatory effects. However, confirmatory work rapidly showed the effect of statins on hsCRP to be a consistent and important class effect. Studies of atorvastatin, cerivastatin, lovastatin, pravastatin, and simvastatin have shown that, on average, median hsCRP concentrations decline 15% to 25% as early as 6 weeks after initiation of therapy. Importantly the magnitude of LDL cholesterol reduction caused by statin therapy is minimally correlated with the magnitude of hsCRP reduction. ... 

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