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Low-Density Lipoprotein Cholesterol Levels and Neoatherosclerosis After STEMI: A Secondary Analysis of the CONNECT
Jonas Dominik Häner1, Ryota Kakizaki1, Masanori Taniwaki2
1Department of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
Insights
Achieving target low-density lipoprotein cholesterol (LDL-C) levels after drug-eluting stent (DES) implantation significantly reduces neoatherosclerosis. Lowering LDL-C is crucial for preventing late stent failure and cardiac events in STEMI patients.
Area of Science:
- Cardiovascular Medicine
- Interventional Cardiology
- Biomedical Engineering
Background:
- Neoatherosclerosis is a primary cause of late drug-eluting stent (DES) failure, leading to cardiac events.
- While low-density lipoprotein cholesterol (LDL-C) reduction benefits native coronary arteries, its impact on DES-related neoatherosclerosis is unclear.
Purpose of the Study:
- To investigate the association between achieving guideline-recommended LDL-C levels and the long-term risk of neoatherosclerosis after DES implantation.
Main Methods:
- Post hoc analysis of the CONNECT randomized clinical trial involving 239 ST-segment elevation myocardial infarction (STEMI) patients.
- Patients underwent percutaneous coronary intervention (PCI) with everolimus-eluting stents.
- Neoatherosclerosis was assessed using optical coherence tomography (OCT) three years post-PCI; LDL-C levels were analyzed.
Main Results:
- Of 178 patients assessed at 3 years, 55% achieved target LDL-C levels (mean 48 mg/dL) versus 45% who did not (mean 87 mg/dL).
- Neoatherosclerosis prevalence was significantly lower in patients achieving LDL-C targets (7% vs. 19%).
- On-treatment LDL-C level was an independent predictor of neoatherosclerosis (OR 1.46 per 25 mg/dL increase).
Conclusions:
- Achieving guideline-endorsed LDL-C levels is associated with reduced neoatherosclerosis 3 years after DES implantation for STEMI.
- On-treatment LDL-C level independently predicts neoatherosclerosis, highlighting the importance of lipid-lowering therapy in preventing late stent failure.
Importance:
Neoatherosclerosis represents a major cause of late stent failure and results in cardiac events after drug-eluting stent (DES) implantation. Achieving secondary preventive low-density lipoprotein cholesterol (LDL-C) target levels can reduce plaque progression in native coronary arteries; however, its association with neoatherosclerosis formation remains unclear.
Objective:
To determine whether achieving guideline-endorsed LDL-C levels after DES implantation is associated with reduced risk of long-term neoatherosclerosis formation.
Design, Setting, And Participants:
This is a post hoc analysis of the CONNECT randomized clinical trial conducted at 7 sites in Switzerland and Japan that had randomized 239 patients with ST-segment elevation myocardial infarction (STEMI) to percutaneous coronary intervention (PCI) with biodegradable- or durable-polymer everolimus-eluting stents between June 2017 and June 2020. The prevalence of neoatherosclerosis was assessed with optical coherence tomography (OCT) 3 years after primary PCI. Data analysis for this post hoc analysis was conducted from September 2024 to October 2025.
Intervention:
Patients with STEMI received primary PCI with DES, and statin therapy was recommended according to country-specific guidelines.
Main Outcomes And Measures:
The prevalence of neoatherosclerosis 3 years after primary PCI was compared between patients with vs without achievement of guideline-endorsed target LDL-C levels. A multivariable predictor analysis was performed to determine whether on-treatment LDL-C levels were associated with occurrence of neoatherosclerosis.
Results:
Among 178 patients (mean [SD] age, 63.4 [10.9] years; 27 [15%] female) who underwent OCT at 3 years, 98 patients (55%) achieved the target LDL-C level and 80 patients (45%) did not. The mean (SD) on-treatment LDL-C levels for these groups were 48 (13) and 87 (37) mg/dL, respectively (to convert to millimoles per liter, multiply by 0.0259). The prevalence of neoatherosclerosis was lower in patients who achieved the target LDL-C level as compared with patients who did not (7 patients [7%] vs 15 patients [19%], respectively; odds ratio for those who did not achieve the LDL-C target level, 3.00; 95% CI, 1.19-8.24; P = .02). On-treatment LDL-C level (per 25-mg/dL increase) emerged as an independent determinant of neoatherosclerosis at 3 years in multivariable logistic regression analysis (odds ratio, 1.46; 95% CI, 1.09-2.01; P = .01).
Conclusions And Relevance:
On-treatment LDL-C level emerged as an independent predictor of neoatherosclerosis 3 years after DES implantation for STEMI. Neoatherosclerosis was less frequent among patients who achieved the guideline-recommended on-treatment LDL-C level, underscoring the importance of LDL-C lowering in preventing neoatherosclerosis formation.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03440801.
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