Elsevier

American Heart Journal

Volume 142, Issue 2, August 2001, Pages 211-217
American Heart Journal

Trial Design
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,☆☆

https://doi.org/10.1067/mhj.2001.116959Get rights and content

Abstract

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. (Am Heart J 2001;142:211-7.)

Section snippets

Overview of study design

The A-to-Z Trial is an ongoing, 2-phase, international, multicenter, randomized study (Figure 1) that focuses on 2 management questions for patients with ACS.

. Schematic representation of the study design of the A-to-Z Trial. Patients with nSTE ACS are evaluated for A-phase inclusion and exclusion criteria (T-I). Patients who enter A phase receive tirofiban and are randomized to either enoxaparin or unfractionated heparin for 48 to 120 hours or until stabilized (T-II). Patients are re-evaluated

Discussion

The A-to-Z trial is a single study designed to address 2 separate but temporally related clinical questions concerning the management of patients with ACS. The primary objective examines whether early aggressive simvastatin therapy is superior to an “accepted care” regimen as a prevention measure for nSTE-ACS or STE-ACS patients. The secondary objective examines whether randomization to either enoxaparin or unfractionated heparin affects the outcome of the acute management in patients with

Conclusion

The A-to-Z Trial has 2 distinct aims. The primary aim is to define further the role of statin therapy in the treatment of coronary disease. The secondary aim is to advance acute medical therapy for the stabilization of ACS. The design follows the temporal course of a typical hospital admission for ACS, beginning with initial evaluation and acute therapy, followed by stabilization and secondary evaluation, and concluding with initiation of secondary prevention measures. The results of this study

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  • Cited by (0)

    Guest Editor for this manuscript was Joseph S. Alpert, MD, University of Arizona Health Sciences Center, Tucson, Ariz.

    ☆☆

    Reprint requests: Michael A. Blazing, MD, Duke University Medical Center, Box 3126, Erwin Road, Durham, NC 27710. E-mail: [email protected]

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