高剂量阿托伐他汀药物的安全性

1、Safety of High-Dose Atorvastatin TherapyYinhong High-dose statins lower LDL and C-reactive protein(CRP) levels to a greater degree than low-dose statins. Thus, it is reasonable to expect that higher doses of more potent statins would be most effective in preventing cardiovascular events. High-dose s

2、tatins are not commonly prescribed in clinical practice. Reasons for this include the higher cost of higher doses and the nonlinear relation of statin dose to lowering of LDL, whereby doubling the dose produces a decrease in LDL of only approximately 6%.Risks of Statins The risks of statins that sti

3、ll remain are elevations of hepatic enzymes, myopathy, and possibly cancer.Statins and the liver High doses of lovastatin caused hepatic necrosis in rabbit models, and early clinical studies of lovastatin revealed frequent, but minor, elevations of hepatic enzyme concentrations. If an increase in AL

4、T or AST concentrations 3 times the upper limit of normal (ULN) persisted, then discontinuation of therapy was recommended. The “Warnings” section of the product information is similar for the other statins. Periodic monitoring of AST and ALT is unlikely to prevent the exceedingly rare case of acute

5、 liver failure. Statins and myopathy The most serious risk associated with statins is myositis with rhabdomyolysis. Statins and cancer A worry about statins is the possibility that this class of agents may increase the long-term risk of cancer. A meta-analysis of the first 5 large statin trials reve

6、aled no difference in cancer rates between statin-treated and placebo patients. The foregoing safety considerations support the use of high-dose statins in patients at high risk for coronary or cerebrovascular events, particularly patients with established disease, regardless of their baseline chole

7、sterol levels. The small risk of a serious adverse event in such patients is dwarfed by the large benefit in preventing death, myocardial infarction, stroke. In contrast, statins should be used more conservatively in younger patients who are at very low risk, even when hyperlipidemia is present, bec

8、ause the long-term effects of these drugs are not yet known. Diet and exercise are more appropriate approaches in this population. Although frequent monitoring of liver function is recommended in the product information for statins, this recommendation is now archaic. Minor enzyme elevations are not

9、 clinically significant, and the rare cases of acute liver failure that occur during statin therapy are not preventable by monitoring. Measuring liver enzymes once, together with lipids, 4 to 6 weeks after starting therapy is probably sufficient for the usual patient. Patients who develop minor myalgias should be encouraged to continue treatment. Serious myalgias or muscle weakness necessitate a discontinuation of the statin. The main limitat