Acute myocardial infarction (AMI) is a leading cause of death and disability worldwide. The global epidemiologic burden of AMI continues to rise. According to the World Health Organization, the annual incidence of AMI is approximately 50–200 cases per 100,000 people, and approximately 30% of patients face the risk of recurrent cardiovascular events or death within one year of onset [1]. Although primary percutaneous coronary intervention (PPCI) has significantly improved revascularization efficiency among patients with AMI, adverse outcomes including left ventricular remodeling, reinfarction, and heart failure still occur in approximately 15%–20% of patients due to residual inflammation, oxidative stress, and lipid metabolism disorders [2]. Consequently, optimization of perioperative pharmacologic strategies to further improve long-term outcomes has become an important focus of research in cardiovascular medicine.

In recent years, the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in atherosclerotic cardiovascular disease has garnered substantial attention [3]. Basic research has demonstrated that PCSK9 not only modulates lipid metabolism through promoting low-density lipoprotein receptor (LDLR) degradation but also directly participates in pathological processes, including macrophage activation, plaque destabilization, and cardiomyocyte apoptosis following AMI [4]. PCSK9 inhibitors, represented by evolocumab and alirocumab, have been proven in multiple randomized controlled trials to significantly reduce the incidence of major adverse cardiovascular events (MACE) by effectively lowering low-density lipoprotein cholesterol (LDL-C) levels by approximately 50%–62% and potentially exerting anti-inflammatory effects [5, 6]. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend that patients who have recently experienced acute coronary syndrome (ACS) should first be treated with ezetimibe (Class I recommendation) in addition to intensive statin therapy. If LDL-C levels are still not within the target range, PCSK9 inhibitors may be considered as an additional treatment (Class IIa recommendation) [2].

However, unique clinical challenges exist during the acute phase of ACS, including significant fluctuations in patients’ baseline LDL-C levels caused by stress-induced metabolic changes upon admission, and a delayed maximal lipid-lowering effect of statins, which requires 4–6 weeks of continuous treatment to become apparent. This makes it challenging to accurately evaluate the feasibility of a stepwise lipid-lowering regimen in the early post-PPCI period, and delaying initiation of PCSK9 inhibitors may result in missing the critical window of opportunity to intervene in inflammation and disordered lipid metabolism. Therefore, whether PCSK9 inhibitor therapy should be initiated during the early stages of ACS has become a subject of considerable interest [7]. Several studies published by the European Society of Cardiology (ESC) in 2023 have demonstrated that initiating a combined lipid-lowering strategy involving PCSK9 inhibitors immediately after ACS onset, during hospitalization, or at discharge can rapidly and markedly reduce LDL-C levels, significantly enhancing LDL-C goal achievement rates up to 98% (LDL-C 55 mg/dL), while maintaining a favorable safety profile [8, 9]. However, the routine clinical use of PCSK9 inhibitors is limited by the requirement for injection administration, storage constraints, high cost, availability issues, and dependence on long-term therapy, all of which adversely affect patient adherence. As a result, in clinical practice, many patients receive only a single injection during hospitalization [10]. At the same time, existing clinical evidence has focused primarily on long-term medication regimens, and studies evaluating the single-dose use of PCSK9 inhibitors in the acute phase after PPCI—particularly those based on real-world data—remain scarce. Therefore, the present study was designed to systematically evaluate the efficacy and safety of a single postoperative dose of alirocumab in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing PPCI, using real-world clinical data and propensity score matching (PSM) to construct comparable cohorts. The aim was to provide additional real-world, evidence-based support for intensive acute-phase post-PPCI intervention strategies and to further clarify the potential value of PCSK9 inhibitors in the acute management of STEMI.

In recent years, the importance of early intensive lipid-lowering therapy in ACS has been increasingly emphasized by international guidelines. According to cholesterol management guidelines in Europe, the United States, and China, high-intensity statin therapy should be initiated at the time of hospital admission for patients with ACS, regardless of baseline LDL-C levels. For patients at extremely high risk whose LDL levels remain above target, other lipid-lowering drugs such as ezetimibe should be added as soon as possible, and PCSK9 inhibitors should be introduced when necessary to rapidly reduce LDL-C to guideline-recommended target levels [2, 13]. However, in real-world clinical practice, rates of lipid-lowering therapy intensification and LDL-C target achievement among patients with ACS remain generally low, providing a rationale for earlier initiation of PCSK9 inhibitor therapy [14]. Several clinical studies, including EVACS [15], EVOPACS [8] and EPIC-STEMI [9], have demonstrated that initiating PCSK9 inhibitor therapy at admission significantly reduces LDL-C levels within days following ACS onset, enabling patients to achieve lipid targets rapidly. A meta-analysis of nine studies involving 2869 ACS patients confirmed that early initiation of PCSK9 inhibitor therapy in the hospital setting can rapidly and significantly lower LDL-C levels, improve lipid control rates, and significantly reduce the risk of MACE in the short term, with good safety [16]. These studies suggest that initiating PCSK9 inhibitor-enhanced lipid-lowering therapy in the early stages of ACS onset is a promising strategy. However, in actual clinical application, factors such as the injection route, storage requirements, high cost, and compliance challenges associated with long-term therapy have resulted in low patient adherence and high discontinuation rates. In routine clinical practice, the use of PCSK9 inhibitors is frequently limited to single in-hospital injections [10]. Previous studies have primarily evaluated long-term, multiple-dose regimens, while the short-term and long-term impacts of single-dose administration have rarely been assessed. The present study addresses this gap by evaluating, for the first time, the efficacy and safety of a single dose of alirocumab in patients with STEMI undergoing primary PCI in a real-world clinical setting.

In this real-world, propensity score–matched cohort, the cumulative incidence of MACE over 12 months was numerically lower in the alirocumab group than in the conventional treatment group; however, this difference was not statistically significant in either Kaplan-Meier or Cox regression analyses, and the individual components of the composite endpoint (cardiac death, non-fatal myocardial infarction, unplanned revascularization, malignant arrhythmia, and rehospitalization for heart failure) were also similar between groups. Given the modest sample size (n = 192) and low absolute event count (n = 21), the study was likely underpowered to detect anything other than large treatment effects, as the statistical power of time-to-event analyses is strongly driven by the number of events. Consequently, the observed numerical differences should be regarded as exploratory and hypothesis-generating rather than as evidence of a definite clinical benefit of single-dose alirocumab. Our neutral primary endpoint contrasts with the robust risk reductions reported in large randomized trials of long-term PCSK9 inhibition, such as FOURIER (evolocumab) and ODYSSEY OUTCOMES (alirocumab), in which sustained LDL-C lowering over several years led to significant reductions in MACE. Thus, while our findings are directionally consistent with the pharmacologic effects of PCSK9 inhibition, they do not demonstrate a clinical efficacy signal for a single peri-procedural dose and instead underscore the need for adequately powered, multicenter studies with longer follow-up to clarify whether short-term or peri-PCI PCSK9 inhibition can meaningfully influence prognosis after STEMI.

Although no significant difference in the primary endpoint of MACE was observed, superiority of the alirocumab group was evident across several secondary endpoints: (1) In terms of lipid levels, the LDL-C levels in the alirocumab group were significantly lower than those in the conventional treatment group at 1 month post-PPCI. Nevertheless, the mean LDL-C values observed in the alirocumab group (1.9 $\pm$ 0.6 mmol/L at 1 month) remained numerically higher than the more stringent LDL-C goal of 1.4 mmol/L (55 mg/dL) proposed for many very high-risk patients in recent ESC/EAS and ACC documents. These findings are consistent with real-world data showing that achieving such intensive LDL-C levels can be challenging in routine clinical practice, even among very high-risk patients. In our cohort, all patients received moderate-intensity statin therapy, and ezetimibe was not prescribed, reflecting local treatment patterns during the study period rather than a protocol-mandated exclusion. From a pharmacokinetic standpoint, a single 75 mg subcutaneous injection of alirocumab reaches peak concentrations approximately 5–7 days after administration, has a half-life of about 17–20 days, and can maintain LDL-C lowering for more than 4–8 weeks, which likely contributed to the early reductions in LDL-C observed at 1 month [17]. Although our study demonstrated significant reductions in LDL-C levels in the alirocumab group at 1 month post-PPCI, this did not translate into a statistically significant reduction in MACE at 12 months. In this context, our findings may reflect a therapeutic gap: although early reductions in LDL-C may contribute to short-term plaque stabilization, the lack of sustained PCSK9 inhibition likely limits long-term event reduction. Moreover, when comparing our LDL-C results with current clinical targets, the limitations become clearer. According to the 2023 ESC and ACC guidelines, post-ACS patients are advised to achieve LDL-C levels below 1.4 mmol/L. In our cohort, the alirocumab group achieved a mean LDL-C of 1.9 $\pm$ 0.6 mmol/L at 1 month—significantly lower than the conventional treatment group, but still above the recommended threshold. These suboptimal target attainments, together with the limited duration of PCSK9 inhibition, may explain why no significant difference in MACE was observed in this real-world study. (2) With respect to inflammatory markers, CRP and NLR at 24 hours after PPCI were significantly lower in the alirocumab group than in the conventional treatment group, suggesting that alirocumab may exert anti-inflammatory effects in the acute phase of STEMI, consistent with the anti-inflammatory effects of PCSK9 inhibitors reported in previous basic and clinical studies [18]. However, previous meta-analyses have indicated that PCSK9 inhibitors have no significant effect on systemic inflammatory markers such as serum hs-CRP [19]. This discrepancy may be attributed to differences in the timing of biomarker assessment; prior studies (e.g., FOURIER, ODYSSEY) measured CRP several weeks post-PCI, whereas this study captured inflammatory changes within 24 hours of PPCI—a period marked by high inflammatory activity—suggesting a potential acute anti-inflammatory effect of alirocumab. (3) In terms of cardiac function, LVESV in the alirocumab group was significantly lower than that in the conventional treatment group at 1 year after PPCI, indicating a milder degree of ventricular remodeling after myocardial infarction in the alirocumab group. This reduction is clinically relevant, as LVESV is a sensitive and well-established surrogate for left ventricular remodeling following myocardial infarction. Importantly, a decline in LVESV often reflects the occurrence of reverse remodeling (RR)—a therapeutically driven, favorable change in cardiac geometry and function that rarely occurs spontaneously and is considered the structural foundation for improved symptoms and prognosis across cardiovascular disease treatments [20, 21, 22]. The significant reduction in LVESV in the alirocumab group may therefore indicate that early PCSK9 inhibition not only improved lipid and inflammatory profiles, but also promoted favorable structural remodeling. This aligns with prior studies such as Ziogos et al. [23], which reported that early administration of evolocumab reduced myocardial inflammation and mitigated the increase in LVESV. Taken together, these findings support a mechanistic sequence whereby acute anti-inflammatory action limits early myocardial injury and facilitates subsequent RR. Additionally, this structural benefit was accompanied by a significantly greater improvement in patient-reported quality of life (MIDAS score) at 12 months in the alirocumab group. While LVEF remained unchanged, the observed LVESV reduction and associated improvement in functional outcomes support the notion that reverse remodeling had occurred and was clinically meaningful. Therefore, although LVESV was the only cardiac parameter with significant between-group differences, it represents a key structural marker of therapeutic benefit and potentially favorable long-term cardiac outcomes. (4) In terms of quality of life, at 12 months post-PPCI, the total MIDAS score in the alirocumab group was significantly lower compared to the conventional treatment group (36.6 $\pm$ 7.1 vs. 38.9 $\pm$ 8.2, p = 0.012). Although statistically significant, the absolute difference ($\approx$2.3 points) is modest relative to conventional thresholds for minimal clinically important difference (MCID), which typically range from approximately 5% to 10% of the scale for cardiovascular-specific quality-of-life measures. This suggests that the observed difference, while meaningful statistically, might not fully reach clinical perceptibility at the total score level. However, the subscale analysis revealed clinically meaningful differences within specific domains. The alirocumab group showed significant improvements in Physical Activity (12.8 $\pm$ 3.5 vs. 14.8 $\pm$ 4.0, p 0.001; Cohen’s d $\approx$ 0.80) and Security (9.5 $\pm$ 2.6 vs. 12.0 $\pm$ 3.0, p 0.001; Cohen’s d = 0.89), reflecting substantial gains in daily physical functioning and psychological confidence regarding disease recurrence. These findings are consistent with with previous studies demonstrating improvements in mobility, reductions in anxiety, and overall well-being associated with PCSK9 inhibitors therapy [24, 25]. Other MIDAS dimensions such as Emotional Reaction, Dependency, Diet, Medication Concerns, and Side-effects did not show significant between-group differences, suggesting the quality-of-life benefits from alirocumab are primarily concentrated in improved physical performance and reduced health-related anxiety. Taken together, these subscale findings clarify that the clinical value of alirocumab in improving post-MI quality of life is most pronounced in enhancing physical capability and providing emotional reassurance, even if the between-group difference in the total MIDAS score remains modest.

In addition, the safety analysis showed that the incidence of adverse reactions was low in both groups and that the between-group difference was not statistically significant. Administration of a single dose of alirocumab was not associated with a significant increase in the risk of adverse events. Most adverse events were mild, including injection-site pain and throat discomfort, and all resolved spontaneously within 3 days. This finding is consistent with the safety profile observed after a single dose of alirocumab in healthy subjects.

In summary, this study suggests that, in patients with STEMI undergoing PPCI, postoperative administration of a single dose of alirocumab may provide more effective LDL-C lowering, attenuation of early inflammatory responses, improvement in ventricular remodeling, and enhancement of quality of life than conventional therapy, while maintaining a favorable safety profile. Overall, these real-world findings support the potential clinical value of administering a single dose of alirocumab after PPCI in patients with STEMI.

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

PW: writing—original draft, performed the research. HW: writing—review and editing, analyzed the data. DY: writing—review and editing, designed the research study. ZZ: writing—original draft, Supervision, Conceptualization. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This retrospective cohort study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of the First Hospital of Lanzhou University (Approval No. LDYYLL2025-967). Given the retrospective design of the study and the use of anonymized data, the requirement for informed consent was waived.

Not applicable.

This work was supported by the Clinical Cooperative Pilot: Project of Traditional Chinese and Western Medicine for Major Diseases (no. Administration of State Administration of Traditional Chinese Medicine [2018], no. 3); National Key R&D Program of China (no. 2018YFC1311505); Gansu Provincial Clinical Research Center for Cardiovascular Diseases (no. 18JR2FA005).

The authors declare no conflict of interest.

During the preparation of this work the authors used ChatGpt-5.0 in order to check spell and grammar. After using this tool, the authors reviewed and edited the content as needed and takes full responsibility for the content of the publication.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/RCM47437.