The IMPROVE-IT trial enrolled patients for secondary prevention. Its results are not directly applicable to primary prevention of cardiovascular disease in high-risk patients.
Results also cannot be extrapolated directly to all ACS patients, due to the strict inclusion and exclusion criteria applied in the trial. Similarly, the results are not applicable to secondary prevention of atherosclerotic disease other than after ACS. According to pre-defined criteria of the researchers who designed the study protocol, differences observed between ezetimibe and placebo were clinically irrelevant. Statistical significance was inappropriately attained after imputing data to patients for whom ACS-episode data were lacking. The IMPROVE-IT trial does not provide sufficient evidence supporting the use of ezetimibe in combination with a statin for ACS. The FDA advisory committee recommended prohibiting the pharmaceutical company from promoting the addition of ezetimibe to simvastatin to reduce cardiovascular events.