Ezetimibe: Clinical and scientific meaning of the IMPROVE-IT study

After years of anxious wait, in June of the current year, the results of the clinical trial IMPROVE-IT were published in the New England Journal of Medicine. This was the first study to properly evaluate the clinical impact of adding ezetimibe to statin therapy. Until then, we had known that the combination of ezetimibe with statin enhanced the antihyperlipidemic effect of statins (surrogate endpoint). However, a positive surrogate marker does not necessarily have a guaranteed clinical impact on the therapy. Therefore, the IMPROVE-IT would fill a gap in the literature concerning the effect of ezetimibe on clinical outcomes.

The publication of the ENHANCE study in 2008 created uncertainty about the efficacy of the therapy with ezetimibe. In this randomized, clinical trial including patients with familial hypercholesterolemia, the therapy with ezetimibe added to 80 mg of simvastatin led to greater reductions in LDL cholesterol levels as compared with simvastatin alone. However, the effect was not accompanied by a greater reduction in atherosclerosis, measured by the carotid intima-media thickness (surrogate endpoint). At this point, it became evident that the industry was precipitate in promoting the use of a drug before its effects were demonstrated by clinical outcomes.

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