Expert consensus on the rational clinical use of PCSK9 inhibitors

Abstract

Two proprotein convertase subtisilin/kexin type 9 (PCSK9) inhibitors have been recently approved by both the FDA and the EMA for the treatment of hypercholesterolemia, namely evolocumab and alirocumab. These are fully human monoclonal antibodies that selectively block PCSK9, thus permitting the low-density lipoprotein (LDL) receptor to effectively recycle in the surface of liver cells. The administration of these antibodies leads to robust LDL cholesterol lowering by 50-60% on top of maximum hypolipidemic treatment. At least 4 randomized, placebo-controlled studies are under way and will address the question of whether the administration of these PCSK9 inhibitors is associated with a significant reduction of cardiovascular events. Because of the high cost associated with the use of these medications it is very important to consider which patients may gain the most benefit, at least until the results of outcome studies are available. In this Consensus paper 34 scientists define 3 groups of patients that should be currently considered as candidates for the use of these novel drugs. These include: 1a. Adults with established cardiovascular disease and LDL cholesterol > 100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 1b. Adults with diabetes and established cardiovascular disease or chronic kidney disease or target organ damage and LDL cholesterol > 100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 2. Adults with familial hypercholesterolemia without established cardiovascular disease and LDL cholesterol > 130 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe (evolocumab is also indicated in children above 12 years with homozygous familial hypercholesterolemia), and 3. Adults on high or very high cardiovascular risk who are statin intolerant and have an LDL cholesterol > 100 and > 130 mg/dL, respectively, while on any tolerated hypolipidemic treatment.