C-Reactive Protein Levels and Plaque Regression with Evolocumab: Insights from GLAGOV

Abstract Objective On-treatment levels of high sensitivity C-reactive protein (hsCRP) in statin-treated patients predict plaque progression and the prospective risk of atherosclerotic cardiovascular events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors produce additional LDL-C lowering, reduce plaque burden and improve cardiovascular outcomes in statin-treated patients. It is unknown whether residual systemic inflammation attenuates their favorable effects on plaque burden. Methods GLAGOV compared the effects of treatment for 78 weeks with evolocumab or placebo on progression of coronary atherosclerosis in statin-treated patients with coronary artery disease. Clinical demographics, biochemistry and changes in both the burden (percentage atheroma volume (PAV), total atheroma volume (TAV), n=413) and composition (n=162) of coronary plaque were evaluated in evolocumab-treated patients according to baseline hsCRP strata ( 3mg/L). Results The study cohort comprised 413 evolocumab-treated patients (32% low [ 3mg/L] baseline hsCRP levels). Patients in the highest hsCRP stratum were more likely to be female and had a higher prevalence of diabetes, hypertension, and the metabolic syndrome. LDL-C levels were similar across the groups, however participants with higher hsCRP levels had higher triglyceride and lower HDL-C levels at baseline. At follow-up, the change in PAV from baseline (-0.87% [low] vs. -0.84% [intermediate] vs. -1.22% [high], p=0.46) and the proportion of patients experiencing any degree of regression (65.9% vs. 63.5% vs. 63.1%, p=0.88) was similar across hsCRP strata and when evaluated by levels of achieved LDL-C. There were no serial differences in plaque composition by hsCRP strata. Conclusion The ability of evolocumab to induce regression in statin-treated patients is not attenuated by the presence of enhanced systemic inflammation. This underscores the potential benefits of intensive lipid lowering, even in the presence of heightened inflammatory states.