No Indication for Routine Administration
The authors (1) reach the conclusion—strongly based on the IMPROVE-IT trial (2)—that ezetimibe-statin combination therapy for high-risk patients (and specifically, those with diabetes) with acute coronary syndrome lowers the risk of cardiovascular events as compared to statin monotherapy.
This prospective controlled randomized trial, with a median duration of six years, involved 18 144 patients, 4933 of whom had diabetes (27.2%).
Nonfatal cardiovascular events occurred in 46% of patients in the statin group, and in 40% of the ezetimibe-statin combination group. Thus, the absolute risk reduction (ARR) by ezetimibe addition is 6%. The number needed to treat (NNT) over the course of six years is therefore 17 (e.g., 100 divided by 6).
In other words: of 17 diabetic patients treated with the combination over six years, only one patient has the chance of avoiding an additional cardiovascular event. Thus, 16 patients would have been treated with no additional benefits. This is described by the acronym “NTN” (number treated needlessly), of 15 (16 minus 1). Whether this is clinically relevant should perhaps be decided by each person individually.
It must be particularly emphasized that the combination treatment did not reduce either the cardiovascular mortality or the all-cause mortality for persons with diabetes.
Originally, the trial was to be carried out with 10 000 patients over two years. To avoid a foreseeable negative result, the amount of registered patient information was drastically increased in Amendment 3, to 18 000 patients over a six-year interval (3).
Despite these expansions, no advantages were observed by the combination treatment even for the “non-diabetic” patients. In my opinion, there is still no indication for routine administration of ezetimibe.
Prof. Dr. med. Frank P. Meyer
|1.||Nußbaumer B, Glechner A, Kaminski-Hartenthaler A, Mahlknecht P, Gartlehner G: Ezetimibe-statin combination therapy: efficacy and safety as compared with statin monotherapy—a systematic review. Dtsch Arztebl Int 2016; 113: 445–53 VOLLTEXT|
|2.||Cannon CP, Blazing MA, Giugliano RP, et al.: Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372: 2387–97 CrossRef MEDLINE|
|3.||Blazing MA, Giugliano RP, Cannon CP, et al.: Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: Final baseline characteristics of the IMPROVE-IT study population. Am Heart J 2014; 168: 205–12, e1 CrossRef MEDLINE|