If the IMPROVE-IT Trial Was Positive, as Reported, Why Did the FDA Denied Expanded Approval for Ezetimibe and Simvastatin? An Explanation of the Tipping Point Analysis

Excerpt

In 2015, the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial was published in the New England Journal of Medicine and claimed the addition of ezetimibe to simvastatin reduced the risk of cardiovascular events in patients with a previous cardiovascular event.¹ The benefit in the trial was a 2% absolute or 6.4% relative risk reduction in cardiovascular events in the ezetimibe/simvastatin group as compared with simvastatin alone. This reduction was primarily driven by a reduction in non-fatal myocardial infarction and non-fatal stroke. According to the primary trial publication, IMPROVE-IT achieved its goal of showing a reduction of cardiovascular events in patients taking the ezetimibe/simvastatin combination,¹ yet the U.S. Food & Drug Administration (FDA) thought otherwise, and denied marketing approval for ezetimibe-simvastatin based on these data.² …