The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy

Background The A-to-Z Trial is an ongoing international, multicenter, rando mized study designed to investigate 2 issues concerning contemporary care o f patients with acute coronary syndromes (ACS). The first issue is whether the use of low-molecular-weight heparin versus unfractionated heparin affec ts outcomes and safety when used as a therapy adjunctive to baseline treatm ent with tirofiban and aspirin in patients with non-ST-elevation (nSTE) ACS . The second issue is whether early use of an aggressively dosed statin is superior to a current trial-based "accepted care" regimen of a lower-dose s tatin started 3 to 6 months after an acute event. Methods The study is conceptually and functionally divided into 2 sequentia l parts-the "A" Aggrastat and "Z" Zocar phases. The primary A-phase end poi nt is a composite of all-cause mortality, myocardial infarction (MI), and d ocumented refractory ischemia at 7 days. Both nSTE-ACS patients from the A phase and patients with ST-elevation ACS who meet specific risk criteria ar e eligible to enter the subsequent "Z" (Zocor) chronic phase (Z phase). The primary end point of the Z phase is a composite of cardiovascular death, M I, readmission for ACS, and stroke. The trial will continue until 970 prima ry events have occurred in the Z-phase population. Conclusion This trial is evaluating 2 temporally connected sequences of pha macotherapy For ACS. At completion, trial results will provide definitive e vidence regarding efficacy and safety of early, intensive statin therapy an d better define the role of low-molecular-weight heparin in patients with n STE ACS.