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] reductase inhibitors) have been used for a decade to lower low-density lipoprotein (LDL) cholesterol levels and to improve cardiovascular disease 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 atorvastatin conducted in US and international community- and university-based research centers. In these trials, patients with lipid disorders received atorvastatin at dosages of 10 to 80 mg/d. The majority of patients had moderate to severe hypercholesterolemia and were treated from 4 weeks to more than 24 months.


METHODS
Transaminase and creatine phosphokinase levels and adverse events were recorded.


RESULTS
Atorvastatin was well tolerated; fewer than 2% of the atorvastatin-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 atorvastatin as well as with other statins tested were constipation, flatulence, dyspepsia, and abdominal pain. Approximately 5% of atorvastatin-treated patients had serious adverse events; only 2 of these events were possibly associated with treatment. Thirty patients (0.7%) had confirmed transaminase elevations greater than 3 times the upper limit of the normal range. Most elevations occurred within 16 weeks of beginning treatment. No patients had a conclusive characterization of drug-induced myopathy.


CONCLUSIONS
The safety profile of atorvastatin was consistent with that of all statins tested and was similar to that seen in all compounds of this class.
Black
D M
DM
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co, Ann Arbor, Mich 48105-1047, USA.
Bakker-Arkema
R G
RG
Nawrocki
J W
JW
D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors*; D000924:Anticholesteremic Agents / Q000009:adverse effects*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood; D003402:Creatine Kinase / Q000097:blood*; D005260:Female; D006538:Heptanoic Acids / Q000009:adverse effects*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects; D011758:Pyrroles / Q000009:adverse effects*; D000637:Transaminases / Q000097:blood*
D000214:Acyl Coenzyme A; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D000069059:Atorvastatin; D000637:Transaminases; D003402:Creatine Kinase