Effect of a Monoclonal Antibody to PCSK9 on Low-Density Lipoprotein Cholesterol Levels in Statin-Intolerant Patients

Abstract

EDUCTION OF LOW-DENSITY LIpoprotein cholesterol (LDL-C) is the cornerstone of cardiovascular risk reduction, 1-3 with specific LDL-C goals based on cardiovascular outcome trials. 1-4 Statins are currently the most effective agents for reducing LDL-C levels. 5 However, of approximately 20 million patients treated with statins, 6 an estimated 10% to 20% are unable to tolerate any statins or the higher doses necessary to achieve current LDL-C goals, primarily because of muscle-related side effects. 7 The most effective and frequently used alternative is ezetimibe, a cholesterol absorption inhibitor that reduces LDL-C levels by 18%, 8 which alone is unlikely to achieve LDL-C goals and is more commonly used in combination with statins. 9 However statinintolerant patients have a need for more effective LDL-C-lowering therapies. Proprotein convertase subtilisin/ kexin type 9 (PCSK9) plays a pivotal role in cellular cholesterol homeostasis, in which it mediates the binding and trafficking of LDL receptors. 10 Gain-offunction mutations result in hypercholesterolemia, while loss-of-function mutations are associated with reduction in

Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta‐Analysis of 35 Randomized Controlled Trials

“…A total of 138 study arms from 35 studies were analyzed, comprising 45 539 patients (Table S1). 5, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 Alirocumab was used in 18 studies (28 treatment arms), and evolocumab was used in 17 studies (39 treatment arms; Figure 1); placebo was the most common control used (52 control arms), with ezetimibe used in 17 arms, and standard therapy in 2 arms. Eight studies were of an exclusively FH population, and 5 studies included only patients intolerant to statins.…”

Lipids, blood pressure and kidney update 2014

“…PCSK9 inhibitors -evolocumab and alirocumabseem to be the safe and very effective alternative for the high risk patients with statin intolerance [66,67], however bococizumab is still under development to treat statin intolerance (NCT Trial Identifier: NCT02135029). Another option is ezetimibe, especially now, when we have strong CV data supporting its efficacy and safety [6,68].…”

Inhibición de la proproteína convertasa subtilisina/kexina tipo 9 en el tratamiento de la hipercolesterolemia

“…Hay que destacar el estudio GAUSS (NCT01375764), que incluyó a 160 pacientes con intolerancia a las estatinas, en el que la reducción de cLDL fue de un 41-51% en los pacientes que recibieron evolocumab en monoterapia, del 63% en los que recibieron evolocumab más ezetimiba y solo del 14% en los tratados sólo con ezetimiba. La incidencia de eventos adversos fue similar en todos los grupos 14 .…”