The Aggrastat to Zocor study, or A to Z study, phase Z has assessed whether early intensive Simvastatin treatment had advantages over a delayed conservative Simvastatin strategy in ACS ( acute coronary syndromes ) patients.

A total of 4497 ACS patients ( ST-segment elevation MI [STEMI], non-STEMI, and unstable angina ) were enrolled in this multicenter study carried out in 41 countries.

Patients were randomized to 40 mg/d Simvastatin ( 1 month ) followed by 80 mg/d, or to placebo ( 4 months ) followed by Simvastatin 20 mg/d for the duration of the follow-up ( 6 to 24 months ).

After 2 years, no significant differences were observed in the composite end point of death, myocardial infarction, stroke, and unstable angina requiring readmission, between the two arms of the study. Statistically significant differences were found in the secondary end point of heart failure.

Myopathy ( creatine kinase >10 times the upper limit of normal associated with muscle symptoms ) occurred in 9 patients ( 0.4% ) receiving Simvastatin 80 mg/d, in no patients receiving lower doses of Simvastatin, and in 1 patient receiving placebo.

The trial did not achieve the prespecified end point. However, among patients with ACS, the early initiation of an aggressive Simvastatin regimen resulted in a favorable trend toward reduction of major cardiovascular.

de Lemos JA, JAMA. 2004; 292 :1307-1316

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