Comparative Effects of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition and Statins on Postprandial Triglyceride-Rich Lipoprotein Metabolism

Objective— Inhibition of PCSK9( proprotein convertase subtilisin/ kexintype 9) and statins are known to lower plasma LDL (low-density lipoprotein)-cholesterol concentrations. However, the comparative effects of these treatments on the postprandialmetabolism of TRLs (triglyceride-rich lipoproteins) remain to be investigated. Approach and Results— We performed a 2-by-2 factorial trial of the effects of 8 weeks of subcutaneous evolocumab(420 mg every 2 weeks) and atorvastatin(80 mg daily) on postprandialTRL metabolism in 80 healthy, normolipidemic men after ingestion of an oral fat load. We evaluated plasma total and incremental area underthe curvesfor triglycerides, apo ( apolipoprotein)B-48, and VLDL (very-LDL)-apoB-100. We also examined the kinetics of apoB-48 using intravenous D3-leucine administration, mass spectrometry, and multicompartmental modeling. Atorvastatinand evolocumabindependently lowered postprandialVLDL-apoB-100 total area underthe curves( P P P P P P Conclusions— In healthy, normolipidemic men, atorvastatindecreased fasting, and postprandialapoB-48 concentration by accelerating the catabolism of apoB-48 particles and reducing apoB-48 particle secretion in response to a fat load. Inhibition of PCSK9with evolocumabhad no significant effect on apoB-48 metabolism.