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Purpose: In the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), simvastatin/ezetimibe combination was associated with a 6% relative risk reduction in the combined cardiovascular outcome compared with simvastatin alone in patients with acute coronary syndrome. Given strict inclusion criteria (low-density lipoprotein cholesterol 50-125 mg/dL and no use of statins more potent than simvastatin 40 mg), the implications of this important trial in routine acute coronary syndrome care are unknown.Methods: We identified patients with acute coronary syndrome from the Veterans Affairs health care system over a 5-year period and determined what proportion would be candidates for ezetimibe on the basis of IMPROVE-IT criteria. We then evaluated what proportion could potentially see an increase in ezetimibe use if IMPROVE-IT criteria are not strictly followed.Results: Of 219,625 patients with acute coronary syndrome, 69,508 (31.6%) would qualify for ezetimibe on the basis of strict criteria. Among those who did not meet IMPROVE-IT criteria (n = 150,117), ezetimibe could potentially be prescribed by clinicians in a further 28% of patients (n = 61,635) using statins more potent than simvastatin 40 mg, 7.1% of patients (15,527) with a documented statin intolerance, and 10.4% of patients (22,758) with low-density lipoprotein cholesterol >125 mg/dL.Conclusions: Our results provide a first look at the implications of this trial in a large health care system. Although 31.6% of patients would qualify for ezetimibe, there is a large potential for an increase in ezetimibe use in acute coronary syndrome outside of the strict trial inclusions. These findings call for a discussion on ezetimibe's role in patients with acute coronary syndrome already taking high-intensity statins or those with statin intolerance. [ABSTRACT FROM AUTHOR]