Dose Up-Titration of a Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor for Markedly Elevated Lipoprotein(a)...

Lipoprotein(a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors modestly reduce Lp(a) levels, evidence regarding their dose-dependent effects on patients with extremely high Lp(a) levels is limited. A 69-year-old woman was diagnosed with dyslipidemia because of high low-density lipoprotein cholesterol (LDL-C) levels (>180 mg/dL) and was initiated on atorvastatin at a dose of 10 mg/day. Two years later, she developed a myocardial infarction, and heterozygous familial hypercholesterolemia was subsequently diagnosed. Eight years later, despite achieving optimal LDL-C levels using high-intensity statin therapy, ezetimibe, and a half-dose of a PCSK9 inhibitor (evolocumab 140 mg monthly), her Lp(a) levels remained high. Up-titration of evolocumab from 140 mg monthly to 140 mg every two weeks resulted in a 34.7% reduction in Lp(a) levels; however, the value only decreased to 82.5 mg/dL. This case indicates a dose-dependent effect of PCSK9 inhibitor therapy on Lp(a) reduction; however, the magnitude of lowering may be insufficient in patients with extremely high baseline Lp(a) levels.