Objective: Whether inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the regression of coronary atherosclerotic plaque in statin-treated individuals remains unclear. This study examined whether PCSK9 inhibitors combined with statin therapy could increase atherosclerotic plaque regression compared with statin therapy alone.
Methods: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), the database Clinical trials, and the Web of Science were searched to report the coronary atherosclerotic plaque of PCSK9 inhibitors using intravascular ultrasonography (IVUS) or optical coherence tomography (OCT) in statin patients. The weighted mean difference (WMD) of the random-effects/fixed-effects model was used to pool data that satisfied our inclusion criteria obtained from the included studies.
Results: When compared with statin therapy alone, pooled studies revealed that PCSK9 inhibitors combined with statin therapy significantly decreased percent atheroma volume (PAV) (WMD: -1.06%, 95% confidence interval [CI]: -1.39 to -0.73; P<0.001) and total atheroma volume (TAV) (WMD: -6.38 mm, 95% CI: -10.12 to -2.64; P=0.001). Moreover, the fibrous cap thickness (FCT) of the coronary atherosclerotic plaque increases to 21.31 um (WMD: 21.31, 95% CI: 7.08 to 35.53, P<0.001), and the maximum lipid arc decreases 10.9° (WMD: -10.9, 95% CI: -15.24 to -5.34, P<0.001).
Conclusion: In our systematic review and meta-analysis, PCSK9 inhibitors combined with statin therapy were found to be more effective than statin therapy alone for slowing coronary plaque progression by decreasing PAV, TAV, and increasing FCT, maximum lipid arc.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908469 | PMC |
Circulation
March 2025
State Key Laboratory of Metabolism and Regulation in Complex Organisms, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, China. (Y.G., X.L., X.Z., M.L., M.D., Y.W.).
Background: Low-density lipoprotein (LDL) is internalized into cells mainly through LDLR (LDL receptor)-mediated endocytosis. In an acidic endosome, LDLR is released from LDL and recycles back to the cell surface, whereas LDL is left in the endosome and degraded in the lysosome. Circulating PCSK9 (proprotein convertase subtilisin/kexin 9) binds with LDLR and is internalized into the endosome, similar to LDL.
View Article and Find Full Text PDFMedicine (Baltimore)
March 2025
Department of Critical Care Medicine, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China.
This study assesses the causal effects of antihypertensive and lipid-lowering drugs on inflammatory cytokines using a Mendelian randomization (MR) approach. We conducted a drug-targeted MR analysis using data from large-scale genome-wide association studies and eQTL datasets. SNPs near drug target genes served as instrumental variables to investigate the impact of antihypertensive (angiotensin-converting enzyme inhibitors [ACEIs], ARBs) and lipid-lowering drugs (HMGCR inhibitors, proprotein convertase subtilisin/Kexin type 9 [PCSK9] inhibitors, Niemann-Pick C1-like 1 inhibitors) on inflammatory cytokines.
View Article and Find Full Text PDFJ Thromb Thrombolysis
March 2025
Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy since their first approval in 2011. By unleashing the adaptive immune system, non-cardiac and cardiac immune-related adverse events (irAEs) are common and often pose a challenge to multidisciplinary teams treating cancer patients. A significant body of literature reports accelerated atherosclerosis - a key precursor of acute vascular events (AVEs) - with currently approved ICIs (CTLA-4, PD-1, LAG-3, and PD-L1 inhibitors), and some preclinical research also suggests increased thrombogenicity.
View Article and Find Full Text PDFInt J Epidemiol
February 2025
The Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
Background: High levels of lipoprotein(a) [Lp(a)] have been associated with an increased risk of cardiovascular disease (CVD); however, the effects of Lp(a)-lowering therapy in combination with low-density lipoprotein cholesterol (LDL-C)-lowering treatment or lifestyle improvements on CVD risk remain unexplored.
Methods: We conducted a factorial Mendelian randomization study among 385 917 participants in the UK Biobank. Separate genetic scores were constructed to proxy the effects of Lp(a) lowering, LDL-C lowering through different targets [HMG-CoA reductase, NPC1-like intracellular cholesterol transporter 1, proprotein convertase subtilisin/kexin Type 9, and low-density lipoprotein receptor (LDLR)], as well as improvements in body mass index (BMI), systolic blood pressure (SBP), and lifestyle factors (cigarette smoking, alcohol consumption, and physical activity).
Circ Genom Precis Med
March 2025
Cardiovascular Division, Perelman School for Advanced Medicine, University of Pennsylvania, Philadelphia (M.-J.D.).
Background: Therapies targeting the LPL (lipoprotein lipase) pathway are under development for cardiometabolic disease. Insights into their efficacy-both alone and in combination with existing lipid-lowering therapies-modes of action, and safety of these agents are essential to inform clinical development. Using Mendelian randomization, we aimed to (1) evaluate efficacy, (2) explore shared mechanisms, (3) assess additive effects with approved lipid-lowering drugs, and (4) identify secondary indications and potential adverse effects.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!