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Effect of Intensive Lipid-Lowering Therapy on Coronary Plaque Stabilization Derived from Optical Coherence Tomography: a Meta-analysis and Meta-regression

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Abstract

Purpose

The definitive impacts of intensive lipid-lowering therapy (LLT) on plaque stabilization and the relationship between the key markers during LLT and plaque stability remain unquestioned. Thus, these meta-analysis and meta-regression intend to holistically evaluate the influence exerted by rigorous LLT on the minimum fibrous cap thickness (FCT) and maximum lipid arc as discerned through optical coherence tomography (OCT). This study further scrutinizes the correlation of this impact with variations in high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), or additional parameters within patients diagnosed with coronary artery disease (CAD).

Methods

Comprehensive searches were conducted on platforms including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published until June 1, 2023. The search was language agnostic and targeted RCTs elaborating on the correlation between high-intensity statin therapy or statins used concomitantly with other lipid-lowering medications and the minimum FCT and maximum lipid arc as assessed by OCT. The meta-analyses were executed employing a standard mean difference (SMD) algorithm with random-effects on continuous variables. These methodologies align with the Preferred Reporting Items for Systematic and Meta-analysis (PRISMA) guidelines.

Results

A spectrum of 12 RCTs engaging 972 patients were identified and mobilized for these analyses. Meta-analysis outcomes depicted a conspicuous correlation between intensive LLT and an enhanced minimum FCT (12 studies with 972 participants; SMD, 0.87; 95% CI, 0.54 to 1.21; P < 0.01), reduced maximum lipid arc (9 studies with 564 participants; SMD, −0.43; 95% CI, −0.58 to −0.29; P < 0.01). Meta-regression analysis has determined an association of elevated minimum FCT with decreased LDL-C (β, −0.0157; 95% CI, −0.0292 to −0.0023; P = 0.025), total cholesterol (TC) (β, −0.0154; 95% CI, −0.0303 to −0.0005; P = 0.044), and apolipoprotein B (ApoB) (β, −0.0209; 95% CI, −0.0361 to −0.0057; P = 0.022). However, no significant association was discerned relative to variations in hs-CRP/CRP (β, −0.1518; 95% CI, −1.3766 to −1.0730; P = 0.772), triglyceride (TG) (β, −0.0030; 95% CI, −0.0258 to −0.0318; P = 0.822), and high-density lipoprotein cholesterol (HDL-C) (β, 0.0313; 95% CI, −0.0965 to 0.1590; P = 0.608). Subsequent subgroup meta-analysis demonstrated that high-intensity statin therapy (5 studies with 204 participants; SMD, 1.03; 95% CI, 0.67 to 1.39; P < 0.01), as well as a combinative approach including PCSK9 antibodies and statins (3 studies with 522 participants; SMD, 1.17; 95% CI, 0.62 to 1.73; P < 0.01) contributed to an increase in minimum FCT. Parallelly, high-intensity statin therapy (4 studies with 183 participants; SMD, −0.42; 95% CI, −0.65 to −0.19; P < 0.01) or the combined application of PCSK9 antibodies and statins (2 studies with 222 participants; SMD, −0.98; 95% CI, −1.26 to −0.70; P < 0.01) was evidenced to decrease the maximum lipid arc.

Conclusions

Intensive LLT, mainly high-intensity statin therapy and combined PCSK9 antibody with statin, has a beneficial effect on coronary plaque stabilization derived from OCT in patients with CAD. Coronary plaque stabilization is primarily due to lipid-lowering effect, not anti-inflammatory effect. Moreover, the lipid-lowering effect has nothing to do with the changes in HDL-C and TG, but is mainly related to the reduction of LDL-C, TC, and ApoB.

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Data Availability

The data in the current meta-analysis are publicly available from the original literature and supplementary material.

Abbreviations

LLT:

lipid-lowering therapy

PCSK9:

proprotein convertase subtilisin/kexin type 9

EPA:

eicosapentaenoic acid

DHA:

docosahexaenoic acid

IPE:

icosapent ethyl

CAD:

coronary artery disease

ASCVD:

atherosclerotic cardiovascular disease

ACS:

acute coronary syndrome

SMD:

standard mean difference

RCTs:

randomized controlled trials

OCT:

optical coherence tomography

Minimum FCT:

Minimum fibrous cap thickness

TCFA:

thin-cap fibroatheroma

hs-CRP:

high-sensitivity C-reactive protein

TC:

total cholesterol

TG:

Triglyceride

LDL-C:

low-density lipoprotein cholesterol

HDL-C:

high-density lipoprotein cholesterol

ApoB:

apolipoprotein B

HTG:

hypertriglyceridemia

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Acknowledgements

We would like to thank all participants and all peer reviewers for their opinions and suggestions.

Funding

This research was supported by grant from the National Natural Science Foundation of China (81970262 to PJW).

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Author notes

  1. Sen Liu, Jixin Hou and Jindong Wan contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, 610500, Sichuan, China

    Sen Liu, Jixin Hou, Jindong Wan, Yi Yang, Dan Wang, Dengpan Liang, Xinquan Wang, Peng Zhou & Peijian Wang

  2. Sichuan Clinical Research Center for Geriatrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China

    Sen Liu, Jixin Hou, Jindong Wan, Yi Yang, Dan Wang, Dengpan Liang, Xinquan Wang, Peng Zhou & Peijian Wang

  3. Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, Chengdu, 610500, Sichuan, China

    Sen Liu, Jixin Hou, Jindong Wan, Yi Yang, Dan Wang, Dengpan Liang, Xinquan Wang, Peng Zhou & Peijian Wang

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Contributions

SL and PW conceived and designed this study. SL and JH drafted the first version of the manuscript. PZ and PW provided critical revision of the manuscript for important intellectual content. SL, JH, JW, YY, DW, DL, and XW carried out acquisition, statistical analysis, or interpretation of data. PW provided the funding support.

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Correspondence to Peng Zhou or Peijian Wang.

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Liu, S., Hou, J., Wan, J. et al. Effect of Intensive Lipid-Lowering Therapy on Coronary Plaque Stabilization Derived from Optical Coherence Tomography: a Meta-analysis and Meta-regression. Cardiovasc Drugs Ther (2023). https://doi.org/10.1007/s10557-023-07511-7

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