Clinical Question: Can early initiation of an intensive regimen with simvastatin improve clinical outcomes after an acute coronary syndrome event?
Setting: Inpatient (any location) with outpatient follow-up
Study Design: Randomized controlled trial (double-blinded)
Synopsis: Investigators randomized 4,497 patients with acute coronary syndrome in a double-blind fashion (concealed allocation assignment) to receive 40 mg of simvastatin per day for one month followed by 80 mg per day thereafter, or placebo for four months followed by 20 mg per day of simvastatin. Eligible subjects were 21 to 80 years of age with non–ST-elevation acute coronary syndrome or ST-elevation myocardial infarction with a total cholesterol level of 250 mg per dL or lower. Patients who were receiving statin therapy at the time of randomization and those for whom coronary artery bypass graft surgery or percutaneous coronary intervention was planned within two weeks were excluded. Outcomes were assessed by persons blinded to treatment group assignment.
Follow-up was complete for 99 percent of the subjects for up to two years. Using intention-to-treat analysis, no significant difference was seen between the treatment groups for the composite end point of cardiovascular death, recurrent acute coronary syndrome, and stroke during the first four months. However, from four months through the end of the study the composite end point was significantly reduced: 9.3 percent in the placebo plus simvastatin group compared with 6.8 percent in the high-dose simvastatin-only group (hazard ratio = 0.75; 95 percent confidence interval, 0.60 to 0.95; number needed to treat = 40). Because this outcome was a posthoc analysis (i.e., after investigators completed the study and found no difference in their primary outcomes, they reanalyzed looking for other outcomes for statistical significance), further studies are needed to verify the results. The groups did not differ significantly in all-cause mortality at any time during the two-year follow-up period. Significant myopathy occurred in nine patients (0.4 percent) receiving simvastatin in a dosage of 80 mg per day.
Bottom Line: Early initiation of an intensive regimen using simvastatin may reduce the risk of a secondary adverse cardiovascular outcome following an acute coronary syndrome event. The benefit began only after four months of treatment, and there was no overall reduction in all-cause mortality. (Level of Evidence: 1b)