Lipid-altering efficacy and safety of simvastatin 80 mg/day: Worldwide long-term experience in patients with hypercholesterolemia

Background and Aim: Clinical data suggesting that larger decreases in low d ensity lipoprotein cholesterol (LDL-C) result in greater reductions in coro nary heart disease events have led to the establishment of aggressive LDL-C targets for the treatment of hypercholesterolemia. In view of this, the ef ficacy and safety of a new maximum dose of simvastatin, 80 mg, were evaluat ed in 9 studies involving 2819 hypercholesterolemic patients. This report f ocuses on the combined results from the 4 main or Pivotal studies in which a total of 1936 patients received simvastatin 40 or 80 mg for 36 to 48 week s. Methods and Results: The Pivotal studies had similar randomized, multicente r, controlled double-blind, parallel-group designs. Their combined results demonstrated a significant advantage in the LDL-C-lowering effect for the 8 0 mg close, At week 24, the mean percentage reductions (95% confidence inte rvals) from baseline in LDL-C for the 40 and 80 mg groups were -39.8% (-40. 9 -38.7) and -45.7% (-46.5, -45.0) respectively (p<0.001, between groups), and larger reductions in total cholesterol and triglycerides were also obse rved in the 80 mg group. Both doses were well tolerated. No new or unexpect ed adverse events were observed and the overall clinical event profiles wer e similar in the two groups. Clinically significant hepatic transaminase in creases (>3 times the upper limit of normal/ULN) and myopathy (muscle sympt oms plus creatine kinase increase >10 times ULN) occurred infrequently with both doses. Simvastatin 80 mg had a comparable efficacy and safety profile in women and men as well as in non-elderly and elderly patients Conclusions: Simvastatin 80 mg provides additional LDL-C and triglyceride r eductions compared to the 40 mg dose and has an excellent safety and tolera bility profile, (C) 2000 Medikal Press.