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 sele ction and use of drugs, such as lipid-lowering agents, that are prescr ibed to reduce the risk of clinical events during long periods. Method s: The Scandinavian Simvastatin Survival Study was designed to evaluat e the effects of cholesterol lowering with simvastatin on mortality an d morbidity in patients with coronary heart disease. The 4444 patients aged 35 to 70 years (mean, 58.9 years) with angina pectoris or previo us myocardial infarction and serum cholesterol levels of 5.5 to 8.0 mm ol/L (213-310 mg/dl) receiving a lipid-lowering diet were randomly ass igned to take double-blind treatment with simvastatin, 20 to 40 mg onc e daily, or placebo. In addition to previously reported end-point even ts, 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 y ears). Results: The only clearly drug-related serious adverse event du ring the 5.4-year median follow-up period was a single reversible case of myopathy. The frequencies of persistent elevations of hepatic amin otransferase levels above 3 times the upper limit of normal and of non viral hepatitis in the simvastatin and placebo treatment groups were n ot significantly different. Examination of the lens showed no between- group differences, and no previously unrecognized adverse effects of t he drug were observed. There were no significant between-group differe nces in adverse events in any body system. In particular, the frequenc y of adverse events related to the central nervous system was similar in both groups. Conclusion: The safety profile of simvastatin, 20 to 4 0 mg daily, over 5 years was excellent.