Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study.
BACKGROUND
Long-term safety is an important consideration in the selection and use of drugs, such as lipid-lowering agents, that are prescribed to reduce the risk of clinical events during long periods.


METHODS
The Scandinavian Simvastatin Survival Study was designed to evaluate the effects of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease. The 4444 patients aged 35 to 70 years (mean, 58.9 years) with angina pectoris or previous myocardial infarction and serum cholesterol levels of 5.5 to 8.0 mmol/L (213-310 mg/dL) receiving a lipid-lowering diet were randomly assigned to take double-blind treatment with simvastatin, 20 to 40 mg once daily, or placebo. In addition to previously reported end-point events, detailed clinical and laboratory safety data were collected during a median follow-up period of 5.4 years (range in survivors, 4.9-6.2 years).


RESULTS
The only clearly drug-related serious adverse event during the 5.4-year median follow-up period was a single reversible case of myopathy. The frequencies of persistent elevations of hepatic aminotransferase levels above 3 times the upper limit of normal and of nonviral hepatitis in the simvastatin and placebo treatment groups were not significantly different. Examination of the lens showed no between-group differences, and no previously unrecognized adverse effects of the drug were observed. There were no significant between-group differences in adverse events in any body system. In particular, the frequency of adverse events related to the central nervous system was similar in both groups.


CONCLUSIONS
The safety profile of simvastatin, 20 to 40 mg daily, over 5 years was excellent.
Pedersen
T R
TR
University of Oslo, Norway.
Berg
K
K
Cook
T J
TJ
Faergeman
O
O
Haghfelt
T
T
Kjekshus
J
J
Miettinen
T
T
Musliner
T A
TA
Olsson
A G
AG
Pyörälä
K
K
Thorgeirsson
G
G
Tobert
J A
JA
Wedel
H
H
Wilhelmsen
L
L
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood*; D003327:Coronary Disease / Q000150:complications; D004311:Double-Blind Method; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy; D008148:Lovastatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D019821:Simvastatin
D000924:Anticholesteremic Agents; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin