Proprotein Convertase Subtilisin/Kexin Type 9 and Atherosclerotic Plaque Progression: A Systematic Review and...

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have emerged as a promising class of medications, primarily recognized for inducing potent cholesterol-lowering effects. In addition to the established role of these inhibitors in reducing low-density lipoprotein cholesterol levels, recent studies suggest that PCSK9is may also modify coronary atherosclerotic plaques. Therefore, this meta-analysis aimed to comprehensively synthesize data from relevant clinical studies and trials investigating the effects of PCSK9is on coronary atherosclerotic plaque characteristics.

We performed a literature search for studies assessing the evolution of coronary atherosclerotic plaques after treatment with a PCSK9i compared with a control group. We excluded reviews, editorials, case reports/case series, and studies that did not use PCSK9is or lacked a control group. The main outcomes of interest were changes in percent atheroma volume (PAV), total atheroma volume (TAV), minimal fibrous cap thickness (FCT), lipid arc, and the number of patients with improved PAVs at follow-up. Effect sizes are presented as a standardized mean difference (SMD) or risk ratio (RR) alongside the corresponding 95% confidence intervals (CIs) and were pooled based on a random-effects model. Publication bias was assessed by funnel plot inspection and Egger's regression test.

The literature search yielded 142 results. After applying the exclusion criteria, nine studies were selected for data extraction and inclusion in the meta-analysis. Concerning the intravascular ultrasound findings, PCSK9is significantly reduced the TAV (MD -7.09 mm³, 95% CI -11.36 to -2.81; p = 0.01) and induced non-significant reductions in the PAV (MD -1.91%, 95% CI -5.08 to 1.25; p = 0.17); meanwhile, a greater proportion of patients treated with PCSK9 inhibitors exhibited an improvement in the PAV (RR 1.30, 95% CI 1.19 to 1.42; p < 0.001). For optical coherence tomography parameters, patients treated with PCSK9 inhibitors showed an increase in minimal FCT (MD 36.25 μm, 95% CI 0.75 to 71.75; p = 0.047) and a non-significant decrease in lipid arc (MD -17.64°, 95% CI -49.73 to 14.44; p = 0.14).

This meta-analysis suggests that PCSK9i therapy may be associated with modest favorable changes in selected intravascular imaging markers of coronary atherosclerotic plaque burden and stability.