Are antibodies against PCSK9 the statins of the 21st century?

Abstract

Evaluation of: Koren MJ, Giugliano RP, Raal FJ et al.; OSLER Investigators. Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) randomized trial. Circulation 29(2), 234–243 (2014). PCSK9 degrades LDLR after almost 30 h of function. The OSLER trial tested the mid-term (1 year) safety and efficacy of evolocumab, a human antibody against PCSK9, which prolongs the function of LDLR and reduces LDL-cholesterol (LDL-C) levels. The study included 1104 patients with hypercholesterolemia, after the completion of four different Phase II studies. Regardless of treatment in the parent studies, patients were randomized to subcutaneous evolocumab 420 mg/4 weeks plus standard care including statins (n = 736), or standard care alone (n = 368). Patients who first received evolocumab in OSLER and those on evolocumab in the parent studies had an identical mean decrease (52%) in LDL-C at week 52 (p < 0.0001). In those who discontinued evolocumab on entry into OSLER LDL-C levels returned to baseline levels. In subjects on evolocumab, 96% achieved LDL-C <2.9 mmol/l (100 mg/dl) at any visit vs 32% of participants on standard care, while LDL-C <1.8 mmol/l (70 mg/dl) was achieved in 83 vs 4%, respectively. A total of 2.2% of patients on standard care and 1.2% patients on evolocumab experienced a cardiovascular event. The discontinuation rate of evolocumab due to adverse effects was 3.7%, suggesting excellent safety. These results suggest that evolocumab is safe and effective on a mid-term basis.

Keywords:

• achievement of LDL goals
• antibodies against PCSK9
• heterozygous familial hypercholesterolemia
• LDL receptor
• proprotein convertase subtilisin/kexin type 9
• statin intolerance