PCSK9 Inhibitor Resistance May Be Identified by Plasma PCSK9

HealthDay News — Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) may help assess apparent resistance to PCSK9 inhibitors, according to a research letter published in the Annals of Internal Medicine.

Michael D. Shapiro, DO, from the Oregon Health & Science University in Portland, and colleagues describe changes in plasma PCSK9 levels before and after PCSK9 inhibitor therapy in 17 adult patients with cardiovascular disease (14 patients) and/or familial hypercholesterolemia (nine patients). Before and 3 months after initiation of PCSK9 inhibitor therapy, total plasma PCSK9 levels were measured.

The researchers found that the mean baseline plasma PCSK9 level was 324 ng/mL. Within 5 days of their sixth self-injection, the total plasma PCSK9 levels were 2286 ng/mL in patients with the anticipated greater-than-45% reduction in low-density lipoprotein cholesterol (LDL) levels (median seven-fold increase from baseline levels).

Plasma PCSK9 levels varied, but they increased by at least 3.7-fold in 16 of the patients; pre- and post-treatment values were not overlapping for any of these patients. Two of the patients with familial hypercholesterolemia had markedly attenuated response of LDL cholesterol levels to the PCSK9 inhibitor; 1 of these patients had no change in plasma PCSK9 levels.

“We report a simple method for assessing apparent resistance by measuring total levels of plasma PCSK9 before and after treatment,” the authors write.

Several authors disclosed ties to the pharmaceutical industry.

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Shapiro MD, Miles J, Tavori H, Fazio S. Diagnosing resistance to proprotein covertase subtilisin/kexin type 9 inhibitor [published online November 28, 2017]. Ann Intern Med. doi: 10.7326/M17-2485