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

BACKGROUND

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.

OBJECTIVE

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

METHODS

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.

RESULTS

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.

CONCLUSION

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.