HMG CoA reductase, the rate-limiting enzyme in the mevalonate pathway, is 14 steps away from cholesterol synthesis. Statins dramatically reduce the serum concentration of LDL cholesterol by inhibiting this enzyme, but may similarly lower the concentration of many other compounds in the pathway, including ubiquinone (possibly the mechanism of statin-induced rhabdomyolysis though the evidence is far from conclusive). Certain drugs are important co-factors in statin-induced rhabdomyolysis, notably gemfibrozil and inhibitors of cytochrome P450 3A4. Accurate estimates of the incidence of statin-related rhabdomyolysis are now available, and the variation in incidence of rhabdomyolysis is striking. It is rare (1 per 100,000 person-years) in people taking pravastatin, or simvastatin or atorvastatin monotherapy, and more common (2040 per 100,000 person-years) with certain combinations of statins and other drugs, but it was amazingly high, 10% per person per year, in people taking cerivastatin and gemfibrozil together. It is worrying that so high an incidence of a serious hazard from a combination of two drugs in that any doctor could prescribe for any patient went undetected for so long. In preventing statin-induced rhabdomyolysis, monitoring by measuring serum creatine kinase is worthless. Avoiding certain drug combinations and not using gemfibrozil is most effective. Muscle disorders apart, statins appear remarkably safe drugs. The incidence of liver disease in people taking statins is scarcely elevated, if at all, though peripheral neuropathy is more common.
01 - 05 Apr 2006
European Society of Endocrinology