Ezetimibe and combination of lipid lowering medications: what is their role in the era of PCSK9 inhibitors?
Abstract
Ezetimibe is a well-tested lipid lowering drug with very good additive LDL-cholesterol (LDL-C) reducing efficacy when combined with a statin. We have solid evidence regarding its impact on cardiovascular risk and prognosis (SHARP, IMPROVE-IT trials).
Especially the latter trial with its subsequent analyses showed unambiguously the largest benefit from intensive LDL-C lowering can be expected in the pacients at the highest risk, e.g. those who except having a history of an acute coronary event have also additional risk characteristics (diabetes mellitus, hypertension, stroke, chronic kidney disease etc.). A subanalysis of IMPROVE-IT on patients after coronary artery bypass grafting (CABG) pointed in the same direction - patients at greater risk had 20% reduction of the risk of the primary efficacy outcome.
The safety of ezetimibe has repeatedly been demonstrated and IMPROVE-IT added some new data to this issue. Even patients achieving LDL-C levels as low as 0.8 mmol/l did not have any excess of occurrence of side effects.
The answer to the question in the title of this article can be found in recommendations regarding the new drug class of PCKS9 inhibitors as ezetimibe should preferentially be used in the patients groups prioritized for the use of PCSK9 inhibitors. These are namely patients with familial hypercholesterolemia, statin intolerance and very high risk patients with overt atherosclerosis and accumulation of other risk factors.
These patients typically need aggressive LDL-C lowering by more than 50%, mostly they are well above their target LDL-C levels and, also, most of these is not being treated with statin and ezetimibe combination. Even introduction of novel therapies to clinical practice will not change the position of ezetimibe as it can be expected the new treatments will have to be preceded by statin and ezetimibe combination.