Acute myocardial infarction (AMI) occurs due to thrombus formation on the basis of coronary atherosclerosis, leading to complete occlusion of the lumen, subsequent narrowing, and a series of pathophysiological changes that ultimately result in myocardial ischemia, hypoxia, and necrosis [1] . Acute ST-segment elevation myocardial infarction (STEMI) is a specific type of AMI characterized by significant ST-segment elevation on electrocardiograms. Although data extracted from large and diverse community populations demonstrate that significant shifts in public health policies prioritizing primary prevention strategies for coronary artery disease control/prevention, along with heightened awareness of coronary risk factors, have led to notable declines in the prevalence of myocardial infarction (post-2000) and the incidence of ST-segment elevation (over recent decades) [2] - [4] —specifically, the incidence of STEMI decreased from 121 to 77 per 100,000 between 1997 and 2005 [5] —it remains that over 3 million people still develop STEMI annually worldwide [6] - [9] . For STEMI patients, rapid reperfusion therapy is critical, as it not only reduces the infarct size but also significantly improves ventricular function and long-term prognosis [10] . Studies have shown that percutaneous coronary intervention (PCI) is highly effective in treating STEMI and is widely recommended by authoritative guidelines worldwide [11] - [15] . Thrombolytic therapy is currently the most effective treatment for thrombotic diseases and a major research focus in thrombosis management. It primarily achieves vascular recanalization by dissolving existing blood clots. In recent years, the combination of emergency PCI and intracoronary thrombolysis has gained increasing attention in STEMI treatment. Research indicates that this combined approach is an excellent therapeutic strategy, effectively reducing the risk of no-reflow and slow-flow phenomena in AMI patients with high thrombus burden [16] [17] . Currently, thrombolytic drugs for coronary artery recanalization can be categorized into two types: non-specific fibrinogen activators and specific fibrinogen activators [18] . Although thrombolytic agents such as SK (Streptokinase) and UK (Urokinase) have been widely used in clinical practice with proven efficacy, current thrombolytic drugs still suffer from limitations including high antigenicity, short half-life, low specificity, high cost, and adverse effects such as bleeding and allergic reactions. Therefore, developing more effective, safer, and cost-efficient thrombolytic agents holds significant importance for the treatment of thrombotic diseases. Tenecteplase, as a unique fibrinogen activator, has demonstrated remarkable clinical efficacy. Therefore, this study aims to synthesize existing research and systematically review the progress of tenecteplase in STEMI treatment, providing a theoretical foundation and direction for future investigations.

Fibrinolytic agents can be classified into three generations based on their chronological development and therapeutic efficacy.

a) At position 103, asparagine replaces threonine, extending the half-life to over 20 minutes and enabling a single intravenous bolus injection of 5 - 10 seconds, significantly enhancing thrombolytic speed and convenience.

b) At position 117, glutamine replaces asparagine, increasing specificity by 10 - 14 times, reducing fibrinogen consumption, and improving safety.

c) At positions 296 - 299, four alanine residues replace lysine, histidine, and two arginine residues, boosting resistance to PAI-1 by 80-fold and greatly enhancing thrombolytic activity and therapeutic efficacy [24] [25] .

Although rapid advancements in genetic and enzyme engineering have ushered in a new era for thrombolytic therapy, these agents still face challenges such as persistent adverse effects linked to their indirect thrombolytic mechanisms and high production costs [26] [27] .

As a modern thrombolytic agent, the safety and efficacy of tenecteplase are critical issues in clinical medicine. Adverse effects of tenecteplase, including bleeding, allergic reactions, thromboembolic events, and arrhythmias, are similar to those of other thrombolytic agents. Bleeding, the most common complication of tenecteplase and other thrombolytic therapies, can occur at any site throughout the body, including puncture sites and surgical wounds. Intracranial hemorrhage requires particular vigilance due to its significant association with increased mortality. Data indicate that the incidence of symptomatic intracranial hemorrhage in patients treated with tenecteplase (2.9%) is comparable to that of alteplase (2.7%) [28] . The bleeding risk of tenecteplase further escalates when co-administered with anticoagulants or antiplatelet agents. Clinical studies report that thrombolytic agents like tenecteplase may trigger thromboembolic events and cholesterol crystal embolization. Additionally, ST-segment elevation myocardial infarction (STEMI) patients undergoing thrombolytic therapy may experience arrhythmias associated with tissue reperfusion. The ASSENT-4 trial demonstrated that compared to the PCI-only group, the tenecteplase-plus-PCI group exhibited higher rates of mortality, cardiogenic shock, congestive heart failure, and reinfarction requiring repeat revascularization [29] . However, despite these adverse effects, multiple studies have confirmed the safety profile of tenecteplase. For example, Benedict et al. [30] found in rabbit experiments that tenecteplase did not induce platelet aggregation, thereby maintaining vascular patency and significantly reducing bleeding risks. C. Michael et al. [16] demonstrated in a multicenter randomized controlled trial that low-dose tenecteplase as an adjunct to PCI in STEMI patients is both feasible and safe. Further, Wang Jianyuan et al. [31] found in clinical trials that tenecteplase thrombolysis in STEMI patients achieved significant efficacy, promoted cardiac function recovery, and effectively controlled adverse reactions and vascular events. Comprehensive analysis indicates that tenecteplase exhibits outstanding therapeutic performance and holds great potential for clinical application.

Tenecteplase plays a vital role in STEMI treatment globally. While intracoronary tenecteplase is not widely used internationally, China’s Mingfule (tenecteplase) has been clinically applied since 2015. Although molecularly similar to foreign TNK, differences exist in strain selection and production processes. Clinical trials confirm the benefits of intracoronary tenecteplase in PCI-treated STEMI patients, highlighting its potential as an emerging intervention.

In summary, as a next-generation thrombolytic, tenecteplase demonstrates excellent safety and efficacy, making it a promising candidate for clinical adoption. In STEMI patients, tenecteplase improves cardiac function, enhances recanalization rates, and reduces adverse events. Its superiority over other thrombolytics further underscores its value. Studies have confirmed that tenecteplase exhibits individualized variability in its application across different ST-segment elevation myocardial infarction (STEMI) cases. Furthermore, tenecteplase can be combined with other thrombolytic agents to yield differential effects; however, research in this area remains limited. Thus, tenecteplase warrants further exploration in STEMI treatment.

*Corresponding author.