Author + information
- Luca Mascitelli, MD∗ ( and )
- Mark R. Goldstein, MD
- ↵∗Comando Brigata Alpina “Julia”/Multinational Land Force, Medical Service, 8 Via S. Agostino, Udine, 33100, Italy
Murphy et al. (1) tested the prespecified hypothesis in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) (2) that, in addition to reducing first events in high-risk patients after acute coronary syndrome, combination therapy with ezetimibe plus simvastatin would also reduce total events compared with simvastatin alone.
Unfortunately, even in this secondary analysis (1), most of this reduction was driven by coronary revascularization (an endpoint notoriously subject to preference that falsely inflates benefits) (3), and nonfatal myocardial infarction. In particular, the analysis failed to demonstrate a reduction in cardiovascular mortality despite a large sample size and multiyear patient follow-up. Disturbingly, the effect on total mortality was not mentioned.
A very slight risk reduction of nonfatal myocardial infarction (for every 100 patients treated, 1 nonfatal myocardial infarction could be delayed every 2 years) and nonfatal stroke (for every 100 patients treated, 1 nonfatal stroke could be delayed every 5 years), which did not translate into an overall reduction in cardiovascular mortality among high-risk patients, clearly confirms that adding ezetimibe to simvastatin does not lead to meaningful reductions in important clinical events (4), and that the decision of FDA advisors to reject secondary prevention ezetimibe indication is fully justified (5).
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Murphy S.A.,
- Cannon C.P.,
- Blazing M.A.,
- et al.
- Ferreira-Gonzalez I.,
- Busse J.W.,
- Heels-Ansdell D.,
- et al.
- ↵FDA Advisors. Reject Secondary-Prevention Ezetimibe Indication. Medscape. Dec 14, 2015. Available at: http://www.medscape.com/viewarticle/855958. Accessed January 28, 2016.