De Lemos JA et al. (2004) Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes. JAMA 292: 1307–1316

Results from phase Z of the international A to Z trial have now been reported. This part of the study compared early, aggressive statin therapy in ACS with the standard approach of a delayed, less intensive regimen.

Patients with ACS were randomized to 40 mg/day of simvastatin for 1 month and 80 mg/day thereafter (n = 2,265), or placebo for 4 months followed by 20 mg/day of simvastatin (n = 2,232). Follow-up was for 6–24 months and the primary efficacy endpoint was a composite of cardiovascular death, nonfatal MI, readmission for ACS and stroke.

The trial did not achieve the prespecified endpoint, partly due to a lower than expected number of endpoint events and a high (33%) rate of study drug discontinuation. LDL cholesterol levels were significantly lower in the simvastatin-only group than in the patients taking placebo plus simvastatin. Despite this, there was no statistically significant difference in the primary endpoint rate between the two groups, although there was a trend toward a reduction in the simvastatin only group. Between 4 and 24 months, however, the primary endpoint was significantly lower in the simvastatin only group (hazard ratio 0.75, 95% confidence interval 0.60–0.95, P = 0.02.).

Concluding that an overall trend toward reduction of major cardiovascular events had been shown in the simvastatin-only group, the authors propose that statins should be started early after ACS, at doses higher than the typical starting dose. They caution that myopathy was more common among patients receiving 80 mg/day of simvastatin than those receiving lower doses of the drug.