Pharmacological comparison of the statins.
The statins (3-hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors) represent drugs of first choice for treatment of hypercholesterolemia. The safety and efficacy of atorvastatin (CAS 134523-00-5), simvastatin (CAS 79902-63-9), lovastatin (CAS 75330-75-7), pravastatin (CAS 81093-37-0) and fluvastatin (CAS 93957-54-1) has been well documented. Statins decrease dose-dependently low-density lipoprotein (LDL) cholesterol as well as coronary events and total mortality. Clinical outcome data indicate that for simvastatin the lowest number of treated patients is needed to prevent one major coronary event (NNT 15). Based on an approximately 30% reduction of LDL (valid surrogate parameter) atorvastatin (5 mg/day) and simvastatin (10 mg/day) are the most potent agents whereas 40 mg of lovastatin or pravastatin and 60 mg of fluvastatin are needed to reach this "therapeutic target". While all statins share the same mode of action their pharmacokinetic properties and their susceptibility to drug interactions differ slightly. Agents inhibiting CYP3A4 (e.g. grapefruit juice, itraconazole, cyclosporine) should be discouraged if a patient is on atorvastatin, lovastatin or simvastatin. Likewise, fluconazole interferes with the CYP2C9-mediated hepatic elimination of fluvastatin. Moreover, coadministration of gemfibrozil should be avoided because it seems to increase the very low risk for statin-induced rhabdomyolysis. Several statins are available and their equieffective doses have been defined. Selection of a particular drug should be primarily based on clinical outcome data. However, costs and in certain situations the pharmacokinetic profile including the interaction potential of the statins should be taken into account.
Klotz
Ulrich
U
Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. ulrich.klotz@ikp-stuttgart.de
D000818:Animals; D004347:Drug Interactions; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors