Abstract 14816: PCSK9 Inhibitors Modify Plaque and Reduce Plaque Progression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Introduction: Elevated coronary plaque burden and high-risk plaque characteristics, such as thin fibrous cap, are associated with an increased risk of adverse cardiovascular events. However, there is limited evidence on the effect of PCSK9 inhibitors (PCSK9i) on changes to plaque burden and composition. Hypothesis: We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of standard lipid-lowering therapy with vs. without PCSK9i on plaque burden and phenotype. Methods: We searched PubMed, Embase and Cochrane Central for studies that performed serial intravascular imaging comparing patients with vs. without PCKS9i therapy. Two reviewers independently performed study selection, data extraction and assessment of bias. All outcomes were continuous; thus, we computed pooled mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI). Random-effects models were used. Statistical analysis was performed using Review Manager 5.4.1. Results: We included 1,696 patients from 6 RCTs. The mean follow-up ranged from 36 to 76 weeks. Mean age ranged from 58.4 to 61.8 years; 1,246 (65%) were male; and 368 (21.6%) had previous myocardial infarction. Percent atheroma volume (MD -1.05%; 95% CI -1.32, -0.77%; p<0.001), total atheroma volume (MD -6.33 mm 3 ; 95% CI -10.01,-2.66 mm 3 ; p<0.001), and total lipid index (SMD -0.58; 95% CI -0.90,-0.26; p<0.001) were significantly reduced in patients treated with PCSK9i. The minimum fibrous cap thickness (SMD 0.59; 95% CI 0.26,0.93; p<0.001) was also significantly improved in patients randomized to PCSK9i. Conclusions: Our findings suggests that PCSK9i reduce progression of coronary atherosclerosis and stabilizes plaque, as evidence by favorable changes in percent atheroma volume, total atheroma volume, lipid index of the plaque, and minimal fibrous cap thickness.