Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein secreted by the liver that plays a critical role in regulating low-density lipoprotein cholesterol (LDL-C) levels by modulating the degradation of the low-density lipoprotein receptor (LDLR), and PCSK9 inhibitors have emerged as a groundbreaking class of therapeutic agents in the field of lipid management (1). Historically, the discovery of PCSK9 as a key regulator of LDL-C clearance opened new avenues for addressing dyslipidemia and cardiovascular disease (CVD) (2, 3). Early 2000s genetic studies identified loss-of-function mutations in PCSK9 associated with reduced LDL-C levels and a decreased risk of cardiovascular events, underscoring its therapeutic potential (3). Subsequent research culminated in the development of PCSK9-targeting monoclonal antibodies, marking a milestone in drug design (4).

PCSK9 inhibitors act by blocking the interaction between PCSK9 and LDLR, leading to increased recycling of LDLRs and enhanced clearance of LDL-C (5). This mechanism significantly amplifies the liver's LDL-C removal capacity, surpassing the effects of statins and other lipid-lowering therapies (6). This unique mechanism makes PCSK9 inhibitors a valuable addition to the treatment arsenal for managing dyslipidemia, especially in patients who have not reached target LDL-C levels with standard therapies (7). With robust evidence from clinical trials, PCSK9 inhibitors have demonstrated their efficacy in reducing LDL-C levels and cardiovascular events (8). Additionally, Ongoing research is exploring the use of PCSK9 inhibitors in various patient populations, including those with diabetes (9, 10), chronic kidney disease (11), and refractory dyslipidemia (12).

As PCSK9 inhibitors continue to gain acceptance in clinical practice, real-world data analyses have further supported their long-term safety and efficacy profiles (13). Observational studies and post-marketing surveillance efforts provide valuable insights into the practical clinical utility and benefits of PCSK9 inhibitors in routine clinical settings (14). Moreover, ongoing trials are investigating novel PCSK9 inhibitor formulations, dosing strategies, and combination therapies to optimize their lipid-lowering effects and further reduce cardiovascular risk (10, 15). As research continues to unravel the full potential of PCSK9 inhibitors, their role in reducing cardiovascular risk is likely to be further refined, ultimately enhancing long-term outcomes and the overall well-being of patients with dyslipidemia and CVD.

Given the rapid research expansion in PCSK9, a bibliometric analysis of the field remains conspicuously absent. This study aims to provide researchers with a comprehensive overview of the research background and status of the PCSK9 inhibitor field. In this current study, we employ bibliometric analysis to unveil the landscape of studies, focal points of research, and potential avenues of investigation within the area of PCSK9 inhibitor which lays the groundwork for future research initiatives.

In this research, we conducted a thorough bibliometric analysis to assess the PCSK9 inhibitor literature, identifying key trends, prolific authors like Ray, KK from the UK, and the USA's leading role in publication and citation metrics. Our analysis also highlighted influential entities and journals, providing a framework for future research directions within this scientific domain.

PCSK9 inhibitors represent a breakthrough in lipid-lowering therapy, with considerable implications for CVD management (2). By targeting PCSK9, these agents enhance the hepatic uptake of low-density lipoprotein cholesterol (LDL-C), thereby significantly reducing circulating LDL-C levels (18). This mechanism of action positions PCSK9 inhibitors as a promising adjunct to traditional statin therapy. The role of PCSK9 inhibitors extends beyond LDL-C reduction, as they also modulate levels of lipoprotein(a) [Lp(a)] (19). Recent studies have begun to reveal the impact of PCSK9 inhibitors on Lp(a) levels, offering a new therapeutic approach for patients with elevated Lp(a) levels (20). Elevated Lp(a) is linked to higher risks of coronary artery disease, myocardial infarction, and stroke, and managing it presents a clinical challenge, especially in patients with limited responses to statins (21). Currently, clinical trials have observed a modest reduction in Lp(a) levels due to PCSK9 inhibitors (22). Although the reduction in Lp(a) is modest compared to LDL-C, it could translate into meaningful cardiovascular risk reduction, especially in patients with high Lp(a) (23). The mechanisms underlying PCSK9 inhibitors' impact on Lp(a) are not yet fully elucidated, highlighting a significant gap in our understanding (24). The mechanisms underlying PCSK9 inhibitors' impact on Lp(a) are not yet fully elucidated, highlighting a significant gap in our understanding.

Bempedoic Acid (BA) has emerged as a novel oral lipid-lowering agent that targets cholesterol biosynthesis in the liver, thereby reducing low-density lipoprotein cholesterol (LDL-C) levels through the inhibition of ATP citrate lyase (25). This mechanism distinguishes BA from statins, as it is inactive in muscle tissue, which may translate to a lower risk of myopathy and other muscle-related side effects commonly associated with statin use (26, 27). This characteristic renders BA a viable alternative for patients with hyperlipidemia or ASCVD who are statin-intolerant or require more aggressive LDL-C reduction. The potential of combining BA with PCSK9 inhibitors has been a recent focus, as both drugs lower LDL-C through distinct mechanisms, suggesting a possible synergistic effect (28). Especially, a novel small interfering RNA (siRNA) therapy that targets the PCSK9 gene like inclisiran, reducing PCSK9 gene expression at the mRNA level. Administered via subcutaneous injection twice a year, inclisiran provides sustained LDL-C reduction by decreasing circulating PCSK9 levels, resulting in enhanced LDL receptor recycling. Inclisiran is especially beneficial for patients with familial hypercholesterolemia and those at high cardiovascular risk who require consistent, long-term lipid management.

Moreover, the combined use of these drugs may provide a synergistic effect in reducing the risk of cardiovascular events (29). Early research indicates that this combination may achieve additional LDL-C reduction without exacerbating side effects, providing a promising therapeutic strategy for patients who do not meet LDL-C targets with monotherapy (30, 31). These findings provide new strategies for cardiovascular risk management, especially for patients who respond poorly to conventional treatment methods. While the combination of PCSK9 inhibitors and BA shows promise, it is imperative to continue assessing the safety and tolerability profile in long-term studies (32). Although current evidence suggests that the combination is well-tolerated, a comprehensive evaluation of its safety over extended use is necessary (33). PCSK9 inhibitors and BA demonstrate individual benefits in lowering LDL-C levels and managing CVD risk. While these drugs act on different biological pathways, and their combined application may offer an effective treatment option for patients needing further LDL-C reduction (29, 34). While PCSK9 inhibitors have shown significant efficacy in lowering LDL cholesterol (LDL-C) and reducing cardiovascular events, there are still notable research gaps, particularly regarding long-term efficacy and safety, immunogenicity, deeper mechanistic insights, and population-specific outcomes are essential areas for future research on PCSK9 inhibitors. Addressing these gaps will provide a more comprehensive assessment of PCSK9 inhibitors' clinical value and guide their optimal use in managing cardiovascular diseases.

Percutaneous coronary intervention (PCI) is a primary treatment for coronary artery disease, yet managing post-PCI patients to prevent recurrent cardiovascular events remains a clinical challenge (35). Central to this is achieving and maintaining low levels of LDL-C, which is crucial for reducing the risk of further events (33). Despite the use of statins, many patients fail to reach target LDL-C levels, indicating a need for alternative therapies. PCSK9 inhibitors have shown promise in further reducing LDL-C levels in patients post-PCI, including those who do not adequately respond to statins (30). Clinical studies suggest that these inhibitors can significantly decrease cardiovascular mortality and the risk of repeat PCI, beyond the effects of standard treatments (30). Implementing PCSK9 inhibitors in clinical practice requires a careful evaluation of each patient's LDL-C levels, cardiovascular risk profile, statin tolerance, and economic considerations (36). They are particularly recommended for high-risk patients who have not met LDL-C targets with maximal statin therapy (36, 37). As PCSK9 inhibitors become more established in post-PCI care, the need for long-term data on their safety and efficacy is paramount to ensure optimal patient outcomes.

Peripheral Artery Disease (PAD) is a common vascular condition that, despite traditional treatments such as lifestyle modifications, antiplatelet medications, and statins, many patients continue to experience uncontrolled symptoms (38, 39). PCSK9 inhibitors have emerged as a promising therapeutic option for this patient population. Evidence suggests that these inhibitors not only significantly reduce LDL-C levels but also lower the risk of cardiovascular events in PAD patients (40). Specifically, analyses have shown that PAD patients treated with PCSK9 inhibitors experience a reduced risk of such events compared to untreated counterparts (41). While preliminary, research hints at the potential for PCSK9 inhibitors to enhance walking capacity and overall quality of life in PAD patients, possibly by retarding atherosclerotic progression and improving blood flow to the lower limbs (42). However, the direct correlation between PCSK9 inhibitor therapy and these functional improvements remains understudied and requires further validation (43). Identifying the subset of PAD patients who stand to benefit the most from PCSK9 inhibitor treatment is a crucial area for future research.

Recent research has uncovered that PCSK9 inhibitors not only reduce LDL-C levels but also may positively influence endothelial function, a key early indicator of atherosclerosis and CVD (44, 45). The improvement in endothelial function could be attributed to several mechanisms: PCSK9 inhibitors' ability to lower LDL-C levels can mitigate endothelial cell damage caused by elevated LDL-C, thereby preventing endothelial dysfunction (46). Additionally, these inhibitors may downregulate the expression of inflammatory markers, reducing vascular inflammation and further supporting endothelial health (47). There is also preliminary evidence that PCSK9 inhibitors might have a direct beneficial effect on endothelial cells (48). Clinical trials have corroborated these findings, showing improved endothelial function in patients treated with PCSK9 inhibitors (49). The capacity of PCSK9 inhibitors to enhance endothelial function presents a novel therapeutic strategy in the management of CVD. Future research should focus on elucidating the precise mechanisms through which PCSK9 inhibitors exert these effects. Understanding these mechanisms is vital for optimizing the clinical application of PCSK9 inhibitors to prevent and treat CVD effectively.

In summary, PCSK9 inhibitors represent a groundbreaking advancement in lipid-lowering therapeutics, garnering significant attention and enthusiasm within the scientific community. Future research is expected to focus on several critical areas, including a comprehensive assessment of long-term safety, the development of personalized treatment regimens, the expansion of their therapeutic applications, and the exploration of novel molecular mechanisms and targets. As research progresses, PCSK9 inhibitors are anticipated to play a crucial role in the comprehensive management of dyslipidemia, aiding in both its prevention and the mitigation of its consequences. Their impact is likely to be significant in strengthening our defenses against CVD—one of the foremost global health challenges—and in enhancing the overall efficacy of therapeutic interventions.

In this comprehensive analysis, we have delineated the temporal progression of publication and citation trends, bringing into focus the contributions of distinguished scholars such as Ray, KK from the UK. Our findings have accentuated the United States' preeminence in the arena of PCSK9 inhibitor research, as evidenced by its leading position in both the quantity of scholarly output and the magnitude of citation influence. This study has also provided an in-depth examination of the key countries, institutions, and academic journals that are pivotal to the advancement of knowledge in this field. Moreover, our meticulous analysis of keyword trends has surfaced critical research focal points, which serve as a beacon for future investigative endeavors. Researchers are encouraged to prioritize long-term safety studies, explore non-traditional pathways like inflammation, and conduct targeted trials for special populations, such as those with diabetes or renal disease, to enhance treatment outcomes.