PCSK9 Inhibitor Treatment Increases Very Low-Density Lipoprotein Size

LDL, metabolic, membrane
Results reflect a higher clearance of small atherogenic very-low-density lipoproteins remnant particles, which might contribute to cardiovascular risk reduction beyond low-density lipoprotein cholesterol lowering in clinical routine.

Treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors can increase very low-density lipoproteins (VLDL) size and reduce VLDL-associated apolipoproteins, according to study results published in Vascular Pharmacology. The results indicated that PSCK9 inhibitors may help reduce cardiovascular risk for patients beyond low-density cholesterol (LDL-C) reduction.

The study included participants with different concomitant lipid-lowering therapies for whom PCSK9 inhibitor treatment was indicated (n=350). They received either evolocumab 140 mg or alirocumab 75 mg or 150 mg once every 2 weeks. The researchers separated major lipoprotein fractions by β-quantification. They determined lipid and apolipoprotein compositions at baseline and 4 weeks after initiating PCSK9 inhibitor treatment.

At baseline, mean LDL-C and high-density lipoprotein cholesterol (HDL-C) were 151 and 45 mg/dL, respectively; median VLDL cholesterol, VLDL triglycerides, and lipoprotein concentrations were 38, 148, and 26 mg/dL, respectively.

After 4 weeks of PCSK9 inhibitor treatment, participants’ ratios of triglycerides to apolipoprotein B in VLDL particles increased by 40.2% from 5.4 to 7.5 (P <.0001). The results also indicated that VLDL-associated apolipoproteins E, CII, and CIII were reduced by 29.4%, 16.4%, and 12.4%, respectively (all P <.0001).

After 4 weeks, participants had a 38.6% reduction in total cholesterol (P <.0001), mainly driven by a reduction of LDL-C (−77.2 mg/dL; −50.7%; P <.0001).

“These results reflect a higher clearance of small atherogenic VLDL remnant particles, which might contribute to cardiovascular risk reduction beyond LDL-C lowering in clinical routine,” the researchers wrote.

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Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.


Hollstein T, Vogt A, Grenkowitz T, et al. Treatment with PCSK9 inhibitors reduces atherogenic VLDL remnants in a real-world study [published online March 23, 2019]. Vasc Pharmacol. doi:10.1016/j.vph.2019.03.002