American Journal of Preventive Cardiology (Sep 2020)

C-reactive protein levels and plaque regression with evolocumab: Insights from GLAGOV

  • Adam J. Nelson,
  • Rishi Puri,
  • Danielle M. Brennan,
  • Todd J. Anderson,
  • Leslie Cho,
  • Christie M. Ballantyne,
  • John JP. Kastelein,
  • Wolfgang Koenig,
  • Helina Kassahun,
  • Ransi M. Somaratne,
  • Scott M. Wasserman,
  • Steven E. Nissen,
  • Stephen J. Nicholls

Journal volume & issue
Vol. 3
p. 100091

Abstract

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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 (3 ​mg/L). Results: The study cohort comprised 413 evolocumab-treated patients (32% low [3 ​mg/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.

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