AN OVERVIEW OF THE CLINICAL SAFETY PROFILE OF ATORVASTATIN (LIPITOR),A NEW HMG-COA REDUCTASE INHIBITOR

Background: Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] r eductase inhibitors) have been used for a decade to lower low-density lipoprotein (LDI) cholesterol levels and to improve cardiovascular dis ease and clinical outcomes. Objective: To evaluate the safety profile of atorvastatin (Lipitor). Methods: Data were pooled for 21 completed (2502 patients) and 23 ongoing (1769 patients) clinical trials of ator vastatin conducted in US and international community-and university-ba sed research centers. In these trials, patients with lipid disorders r eceived atorvastatin at dosages of 10 to 80 mg/d. The majority of pati ents had moderate to severe hypercholesterolemia and were treated from 4 weeks to more than 24 months. Main Outcome Measures: Transaminase a nd creatine phosphokinase levels and adverse events were recorded. Res ults: Atorvastatin was well tolerated; fewer than 2% of the atorvastat in-treated patients withdrew due to drug-attributable adverse events. The overall adverse event profile for atorvastatin was similar to that observed with other statins. The most common adverse events with ator vastatin as well as with other statins tested were constipation, flatu lence, dyspepsia, and abdominal pain. Approximately 5% of atorvastatin -treated patients had serious adverse events; only 2 of these events w ere possibly associated with treatment. Thirty patients (0.7%) had con firmed transaminase elevations greater than 3 times the upper limit of the normal range. Most elevations occurred within 16 weeks of beginni ng treatment. No patients had a conclusive characterization of drug-in duced myopathy. Conclusions: The safety profile of atorvastatin was co nsistent with that of all statins tested and was similar to that seen in all compounds of this class.