Improvement of retinal microvascular function after initiation of lipid-lowering therapy with PCSK9 inhibitors - An...

Hypercholesterolemia is associated with endothelial dysfunction. While good evidence exists for the beneficial endothelial effects of statins, less is known on the new class of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

The goal of this study was to study the effects of PCSK9 inhibitors on markers of micro- and macrovascular endothelial function and arterial stiffness.

In this prospective observational study, cardiovascular high-risk patients were measured for retinal microvascular function, brachial artery flow-mediated dilatation (FMD), and arterial stiffness (pulse wave velocity [PWV]; augmentation index [AI]) at baseline and after 3 and 12 months of PCSK9 inhibitor therapy. The primary endpoint was the change in flicker-induced dilatation of retinal arterioles (FID_art) after 12 months compared to baseline.

The final study cohort included 42 patients (mean age 56 ± 12 years; 74% male; 76% coronary artery disease). Low-density lipoprotein (LDL) cholesterol was reduced from 3.8 ± 1.2 to 1.8 ± 0.9 mmol/L after 12 months. Retinal microvascular function (FID_art 2.6% ± 1.6% at baseline vs 3.4% ± 2.3% after 12 months, p = .01) and AI (24% ± 9% at baseline vs 21% ± 12% after 12 months, p = .03) improved significantly on PCSK9 inhibitor therapy. No significant changes were observed for FMD, PWV, and other retinal vascular measurements.

In cardiovascular high-risk patients, PCSK9 inhibition is associated with an improvement of retinal flicker-induced dilatation and AI, thereby linking LDL lowering with improvement of microvascular function.