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

Am Heart J. 2001 Aug;142(2):211-7. doi: 10.1067/mhj.2001.116959.


Background: The A-to-Z Trial is an ongoing international, multicenter, randomized study designed to investigate 2 issues concerning contemporary care of patients with acute coronary syndromes (ACS). The first issue is whether the use of low-molecular-weight heparin versus unfractionated heparin affects outcomes and safety when used as a therapy adjunctive to baseline treatment 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 statin started 3 to 6 months after an acute event.

Methods: The study is conceptually and functionally divided into 2 sequential parts-the "A" Aggrastat and "Z" Zocar phases. The primary A-phase end point is a composite of all-cause mortality, myocardial infarction (MI), and documented refractory ischemia at 7 days. Both nSTE-ACS patients from the A phase and patients with ST-elevation ACS who meet specific risk criteria are 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, MI, readmission for ACS, and stroke. The trial will continue until 970 primary events have occurred in the Z-phase population.

Conclusion: This trial is evaluating 2 temporally connected sequences of phamacotherapy for ACS. At completion, trial results will provide definitive evidence regarding efficacy and safety of early, intensive statin therapy and better define the role of low-molecular-weight heparin in patients with nSTE ACS.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Anticoagulants / administration & dosage
  • Anticoagulants / therapeutic use*
  • Drug Therapy, Combination
  • Enoxaparin / administration & dosage
  • Enoxaparin / therapeutic use*
  • Humans
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / therapeutic use*
  • Myocardial Infarction / prevention & control*
  • Patient Selection
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Research Design
  • Simvastatin / administration & dosage
  • Simvastatin / therapeutic use*
  • Tirofiban
  • Tyrosine / administration & dosage
  • Tyrosine / analogs & derivatives
  • Tyrosine / therapeutic use*


  • Anticoagulants
  • Enoxaparin
  • Hypolipidemic Agents
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Tyrosine
  • Simvastatin
  • Tirofiban