Multimodal assessment of treatment with proprotein convertase subtilisin/kexin type 9 inhibitors combined with statins for regulating coronary artery plaque regression in patients with chronic/acute coronary syndrome: A meta-analysis

Abstract

BackgroundStatins are the standard treatment for coronary atherosclerosis; however, some patients require additional therapies for optimal plaque regression. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i), including monoclonal antibodies and small interfering RNA-based therapies, have shown promise as adjuncts to statins, although their efficacy for coronary plaque regression, as assessed by intravascular imaging, remains uncertain.MethodsWe conducted a meta-analysis to compare the treatment efficacy of statins combined with PCSK9i (PCSK9i group) versus statins alone or statins combined with placebo (control group) in adults with coronary atherosclerosis (INPLASY registration number: INPLASY202550027). Plaque lesions were assessed using intravascular ultrasound, optical coherence tomography, coronary computed tomography angiography, and near-infrared spectroscopy. Lipid profile parameters, including low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lipoprotein(a), were measured and analyzed.ResultsIn total, 11 trials involving 2490 patients (follow-up duration: 12-78 weeks) were included. Meta-regression showed that combination therapy significantly reversed coronary artery plaque (p < 0.001). No significant difference was observed in the atheroma volume between the PCSK9i and control groups; however, fibrous cap thickness increased significantly in the PCSK9i group. Additionally, low-density lipoprotein cholesterol and lipoprotein(a) levels decreased, while high-density lipoprotein cholesterol levels increased after PCSK9i treatment.ConclusionPCSK9i combined with statins effectively promote coronary plaque regression, particularly in patients with acute myocardial infarction, offering a promising approach for managing coronary atherosclerosis.

Keywords: Coronary atherosclerosis; meta-analysis; plaque regression; proprotein convertase subtilisin/kexin type 9 inhibitor; statin.

Figure 1.

Flow diagram of study selection.

Figure 2.

Effects of PCSK9i treatment on LDL-C, HDL-C, and Lp(a) levels. (a) LDL-C level in the control group was higher than that in the PCSK9i group (upper); the absolute change in LDL-C level was also higher in the control group than in the PCSK9i group (lower). (b) HDL-C level in the control group was lower than that in the PCSK9i group (upper); the absolute change in HDL-C level tended to be lower in the control group than in the PCSK9i group (lower) and (c) Lp(a) level in the control group tended to be higher than that in the PCSK9i group (upper); the absolute change in Lp(a) level was significantly higher in the control group than in the PCSK9i group (lower) and PCSK9i: proprotein convertase subtilisin/kexin type 9 inhibitors; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; Lp(a): lipoprotein(a).

Figure 3.

Effects of PCSK9i treatment on plaque burden and plaque regression. (a) The minimum fibrous cap thickness in the control group was lower than that in the PCSK9i group. (b) The maximum lipid arc was significantly higher in the control group than in the PCSK9i group. (c) The atheroma volume showed no significant difference between the control and PCSK9i groups and (d) the maxLCBI4 mm was significantly higher in the control group than in the PCSK9i group. PCSK9i: proprotein convertase subtilisin/kexin type 9 inhibitors; maxLCBI4 mm: maximum lipid-core burden index within 4 mm.

Figure 4.

Effects of PCSK9i treatment on plaque regression in the AMI and stable CAD subgroups. (a) In the AMI subgroup, the minimum fibrous cap thickness in the control group was lower than that in the PCSK9i group; however, in the stable CAD subgroup, the minimum fibrous cap thickness was higher in the control group than in the PCSK9i group. (b) In both AMI and stable CAD subgroups, the maximum lipid arc was significantly higher in the control group than in the PCSK9i group. (c) In both AMI and stable CAD subgroups, the atheroma volume in the control group showed no significant difference compared with that in the PCSK9i group and (d) Funnel plot showing publication bias. PCSK9i: proprotein convertase subtilisin/kexin type 9 inhibitors; AMI: acute myocardial infarction; CAD: coronary artery disease.