The efficacy of proprotein convertase subtilisin/kexin 9 inhibitors for coronary atherosclerotic plaque burden and phenotype: A meta-analysis and trial sequential analysis

BACKGROUND Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors' effects on coronary atherosclerotic plaque stability remain unevaluated, so we assessed their efficacy for plaque stability and regression. METHODS We searched six databases for RCTs comparing PCSK9 inhibitors ± statins versus placebo ± statins. Analyses used Stata 14.0 and trial sequential analysis 0.9.5.10 Beta software. Evidence certainty was assessed via GRADEpro GDT. RESULTS Among 259 screened records, 9 trials (8 articles) were included. Data transformation was required for 6 studies. 2 articles raised some concerns, 6 showed low risk. PCSK9 inhibitors therapy significantly reduced PAV versus controls (P=0.03) with high heterogeneity due to some concerns risk of bias, was low-certainty evidence. PCSK9 inhibitors significantly increased minFCT versus controls (P<0.01) with high heterogeneity due to <50 participants, was moderate-certainty evidence. No significant intergroup difference in normalized total atheroma volume was observed (P=0.89) with high heterogeneity due to duration<52-week, was moderate-certainty evidence. No significant intergroup difference in minimum lumen area was observed (P=0.48) with low heterogeneity and moderate-certainty evidence. PCSK9 inhibitors reduced maxLiA versus controls (P=0.03) with low heterogeneity and moderate-certainty evidence. TSA confirmed insufficient power for plaque regression (PAV), necessitating larger trials, whereas stability (minFCT) may achieved supportive evidence. CONCLUSIONS High-risk patients with imaging-confirmed vulnerable plaques could benefit from earlier PCSK9 inhibitor initiation, even when statins achieve LDL-C targets.