Inclisiran in Cardiovascular Health: A Review of Mechanisms, Efficacy, and Future Prospects

Introduction

Data from the Global Burden of Disease Database (GBD) in 2019 indicate that 61% of cardiovascular disease (CVD) is attributable to atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia identified as the second leading risk factor for ASCVD [1]. From a large number of clinical studies, genetic tests, and epidemiological investigations, it has been concluded that the main factor contributing to these risks is elevated levels of cholesterol in the body. Hypercholesterolemia induces alterations in arterial endothelial permeability, facilitating the migration of low-density lipoprotein cholesterol (LDL-C) into the arterial wall. Within the arterial wall, LDL-C binds to the low-density lipoprotein receptor (LDLR), resulting in its absorption and retention. Subsequently, LDL-C undergoes oxidation and is modified into apolipoprotein B, which is then recognized by scavenger receptors on macrophages. This recognition prompts endocytosis, leading to the transformation of macrophages into foam cells. Foam cells initiate inflammatory responses through the secretion of various cytokines. In response, smooth muscle cells in the arterial intima proliferate and produce collagen, contributing to coronary arteriosclerosis and cardiovascular disease [2]. As LDL-C is the primary target for blood lipid intervention, further research and discussion are needed to determine how to effectively control blood lipids within a specified target range based on ASCVD risk stratification. How to keep cholesterol in the required range is particularly important for the primary and secondary prevention of cardiovascular events in patients with dyslipidemia, especially hypercholesterolemia [3,4].

Currently, statins, the most commonly used medications for lowering cholesterol, have been shown to significantly reduce the risk of ASCVD events and reduce LDL-C levels by an average of 27% in studies [5]. Numerous meta-analyses of clinical studies have shown that in order to reduce the risk of CVD, LDL-C levels should be controlled as low as possible and that there is no lower limit to this level [6]. Other adjunctive therapeutic options are needed for patients who cannot achieve LDL-C control or who cannot tolerate statins. As an effective target for reducing LDL-C, protein convertase subtilisin/kexin type 9 (PCSK9) indirectly influences plasma LDL levels primarily by regulating the expression of LDLR on the cytoplasmic membrane [7,8]. Consequently, blocking the binding of PCSK9 to LDLR is crucial for controlling LDL-C levels. Current research and development of therapeutic agents primarily focus on small interfering RNA (siRNA) and monoclonal antibodies. Monoclonal antibodies are proteins that bind to PCSK9, thereby reducing serum LDL levels by inhibiting the interaction between PCSK9 and LDLR [9]. A notable example of this class of drugs is evolocumab, which has been shown to significantly decrease LDL-C levels and the incidence of adverse cardiovascular events in patients with dyslipidemia [10,11]. However, the requirement for frequent administration poses challenges to patient treatment compliance. Moreover, its suboptimal performance, high cost, and limited applicability in certain patient populations have restricted its use in clinical lipid-lowering treatment. In contrast, siRNA targets the expression of the PCSK9 gene in liver cells, inhibiting the secretion of PCSK9 and thereby reducing LDL-C levels [12,13]. Nevertheless, as an emerging lipid-lowering therapy, siRNA treatment requires further clinical trial data to establish its long-term safety, efficacy, applicability, and potential adverse reactions.

Inclisiran represents a pioneering siRNA-based therapy primarily used for the adjuvant treatment of individuals with primary hypercholesterolemia or mixed dyslipidemia. Currently, the ORION clinical trial, which is being conducted across multiple countries, is assessing the long-term safety and efficacy of inclisiran, including its use in adolescent patients with familial hypercholesterolemia (FH) and other special populations. In this article, we aim to review inclisiran with respect to its mechanism of action, safety profile, adverse reactions, applicability, and long-term efficacy. This article analyzes the advantages and disadvantages of inclisiran over conventional lipid-lowering therapies, and describes its clinical pharmacodynamics and benefit-risk assessment based on evidence-based evidence in order to provide guidance to clinicians and clinical pharmacists in formulating an optimal lipid-lowering regimen. A comprehensive summary of the research on inclisiran is presented, identifying future potential and current constraints that need to be overcome.

Inclisiran Mechanism of Action

siRNA interferes with the expression of specific genes that possess complementary nucleotide sequences by promoting the degradation of post-transcriptional mRNA, thereby preventing translation [14]. Research indicates that inclisiran, a long-acting synthetic siRNA, selectively targets PCSK9. Upon entering the bloodstream, it first binds specifically to N-acetylgalactosamine and the asialoglycoprotein receptor on the liver cell membrane, facilitating its entry into liver cells. Subsequently, inclisiran associates with the RNA-induced silencing complex and binds to the mRNA encoding the PCSK9 protein, mediated by the antisense strand, thus inhibiting the production of PCSK9 protein. PCSK9 is a protein that regulates the expression of LDLR on the surface of hepatocytes [15–18]. Consequently, inclisiran’s inhibition of PCSK9 indirectly enhances the expression of LDLR, resulting in a hypolipidemic effect. The current proposed mechanism of action of inclisiran in treating hyperlipidemia is illustrated in Figure 1.

Analysis of Current Hot Keywords Related to Inclisiran

Keyword co-occurrence analysis, after consolidating synonyms, used the VOSviewer tool to summarize 1,194 key terms. Subsequently, a statistical analysis of the frequency of these key terms was conducted, and a keyword co-occurrence network was constructed based on VOSviewer. From the high-frequency keywords ranked in the top 22 (Table 1) and the keyword co-occurrence network (Figure 2), it is evident that besides the search term, efficacy, PCSK9, safety, and risk are the most frequently occurring keywords. The efficacy, safety, and risk of inclisiran in patients with hypercholesterolemia are currently the most prominent topics within this domain. This suggests that ongoing research related to inclisiran primarily focuses on clinical trials, with FH and ASCVD patients being the primary beneficiaries of inclisiran studies. Controlling lipid levels is a fundamental objective of inclisiran research. Double-blind clinical trials remain the most widely used research method in this field, and comparative studies between inclisiran and the traditional lipid-lowering therapy, evolocumab, also garner significant attention.

Summary of Clinical Studies of Inclisiran

EFFICACY:

Dose-response effects were evaluated in multiple phase I/II clinical studies, demonstrating that PCSK9 and LDL-C levels improved in patients treated with inclisiran at various doses. In the multi-ascending dose clinical study ORION-1, it was observed that patients receiving 300 mg of inclisiran sodium at baseline and again at 90 days, followed by injections every 180 days, achieved the most significant LDL-C reduction, with a decrease of 48% to 51% [19,20].

SAFETY AND TOLERABILITY:

Inclisiran is a highly specific protein that effectively targets the reduction of LDL-C, significantly minimizing off-target effects and not producing any obvious adverse reactions [21]. In an analysis of 3 clinical studies, 77.3% of patients in the control group and 78.0% of patients in the inclisiran treatment group experienced at least 1 treatment-related adverse event. Serious adverse events occurred in 23% of patients in the control group and 20.4% of patients in the inclisiran treatment group. The adverse events more commonly observed in the inclisiran group included nasopharyngitis, arthralgia, back pain, urinary tract infection, diarrhea, bronchitis, and injection site reactions. The incidence rates of injection site reactions were 1.8% in the control group and 8.2% in the inclisiran treatment group. Local injection site reactions were the predominant type, all of which were mild to moderate and had no lasting effects [22]. There was no significant difference in the incidence of adverse events between the inclisiran and control groups across all age categories. However, the elderly population constituted the majority of adverse events in both groups. The recent ORION-13 and ORION-16 studies included 162 adolescent patients with FH (12 heterozygous FH [HeFH] patients in the ORION-13 study and 150 HoFH patients in the ORION-16 study). The results of these relevant studies have not yet been published. Should these results demonstrate good safety and tolerability, they may further support the safety profile of inclisiran in the adolescent population, addressing existing research gaps [23].

LONG-TERM SAFETY:

The ORION-8 study serves as a continuation of the long-term efficacy and tolerability follow-up for patients involved in the phase II (ORION-3) and phase III (ORION-9, ORION-10, and ORION-11) inclisiran lipid-lowering trials. Among these patients, the mean exposure to inclisiran, including the parent trials, was 3.7 years, with a maximum exposure of 6.8 years. The mean percentage change in LDL-C levels was −49.4% (95% CI: −50.4, −48.3). The incidence of injection site adverse events during treatment was reported at 5.9%, all classified as mild to moderate, and the proportion of patients with inclisiran-related anti-drug antibodies was 5.5% [24]. These results indicate that inclisiran can maintain good efficacy, tolerability, and safety during long-term lipid-lowering treatment in patients.

SAFETY IN PATIENTS WITH COMORBIDITIES:

The lipid-lowering effect of inclisiran is also applicable to patients with diabetes with poor blood lipid control, with the incidence of adverse events being generally similar between diabetic and non-diabetic groups [25]. The ORION-6 trial evaluated the safety of inclisiran in patients with hyperlipidemia across varying degrees of liver impairment (Child-Pugh grades). This study recruited 28 patients, of whom 12 (42.9%) experienced a total of 36 adverse events: 1 patient with normal liver function (8.3%); 8 patients with mild liver function impairment (80.0%); and 3 patients with moderate liver function impairment (50.0%). The primary adverse event reported was cough. Inclisiran was found to be safe and tolerable in patients with mild to moderate hepatic impairment. This study indicates that the lipid-lowering efficacy of inclisiran is not adversely affected by liver function impairment, and there is no need for dosage adjustment in patients with mild or moderate liver damage [26]. This finding provides valuable guidance for formulating inclisiran treatment dosages in patients with liver function impairment. However, data on patients with severe liver function impairment are lacking, suggesting that future studies may address this gap. The ORION-7 phase I and ORION-1 phase II studies assessed the pharmacodynamic properties of inclisiran in patients with renal impairment. In the ORION-7 study, inclisiran demonstrated similar lipid-lowering effects across patients with mild, moderate, and severe renal impairment, with drug concentrations completely eliminated 48 h after administration in all groups. In the ORION-1 study, the efficacy of inclisiran on blood lipids and PCSK9 was found to be independent of renal function impairment. The incidence of adverse events among patients with mild to moderate renal impairment in the 2 studies was generally comparable, and the occurrence of injection site adverse reactions was low. These studies confirmed that the efficacy of inclisiran remains unaffected by renal function impairment, demonstrating strong safety and tolerability in patients with mild to moderate renal impairment [27]. However, for patients with severe renal impairment, the limited sample size precludes drawing any definitive conclusions.

SAFETY IN SWITCHING THERAPY:

ORION-3 is a 4-year open-label extension study based on the phase II ORION-1 trial. The inclisiran group will continue to receive 2 injections (284 mg inclisiran subcutaneous injection) annually. The switching treatment group will receive treatment every 2 months during the first year, followed by 2 injections (284 mg inclisiran subcutaneous injection) annually for the subsequent 3 years. Among the participants, 233 patients (80%) in the inclisiran-only group and 80 patients (87%) in the switch group completed the full 4-year observation period. During long-term treatment, the reduction rates of LDL-C concentration and PCSK9 levels in both patient groups were generally similar, with a relatively stable maintenance status. Regarding the incidence of adverse events, the rate of serious adverse events in the inclisiran treatment group was 37%, primarily due to nasopharyngitis, while the conversion group reported a rate of 34%, mainly associated with hypertension [28]. This study demonstrates that patients switching to inclisiran and continuing treatment in clinical practice have not experienced any negative effects on drug efficacy or safety.

In comparison to traditional lipid-lowering medications, inclisiran demonstrates superior safety and tolerability, eliminating the necessity for dose adjustments in patients with specific complications, such as those with liver and kidney impairments. Furthermore, during the clinical treatment process, adjusting the treatment plan to include inclisiran does not exacerbate the patient’s disease burden.

DRUG COMBINATION APPLICATION:

The 2023 version of the Chinese blood lipid management guidelines emphasizes that the decision to initiate drug combination therapy in clinical practice generally depends on the type of dyslipidemia, as well as the baseline levels and target values to be achieved. Statins remain a primary class of lipid-lowering medications. For patients whose lipid levels do not reach the target despite the use of moderate-intensity statins, the addition of cholesterol absorption inhibitors or PCSK9 inhibitors can be considered [29]. Furthermore, the 2023 American Heart Association/American College of Cardiology guidelines for chronic coronary artery disease have classified inclisiran as a level 2b recommendation for use alongside statins when ezetimibe and PCSK9 monoclonal antibodies are not tolerated as complementary treatments [30]. The recent ORION-10 and ORION-11 studies recruited 1561 and 1617 patients with ASCVD or ASCVD risk equivalents, respectively. All patients were treated with the maximum tolerated doses of statins and cholesterol absorption inhibitors. Despite these treatments, LDL-C levels remained challenging to control. Following grouping, patients received either inclisiran (284 mg) or a placebo. In the ORION-10 study, inclisiran resulted in a 52.3% reduction in LDL-C levels by day 510, while in ORION-11, a 49.9% reduction was observed. The adverse event profile for patients treated with inclisiran was comparable to that of the placebo group, with between-group differences of 1.7% in the ORION-10 trial and 4.2% in the ORION-11 trial. Although injection site reactions were more prevalent in the inclisiran group than in the placebo group, these reactions were generally mild to moderate and did not necessitate intervention. Importantly, both trials reported no significant differences in the occurrence of serious adverse events between the treatment groups [31]. These 2 studies demonstrate that patients receiving adjuvant treatment with inclisiran, in conjunction with statin therapy and a cholesterol absorption inhibitor, can achieve greater lipid-lowering efficacy without increasing the risk of adverse events. Consequently, when a patient’s blood lipid levels do not reach the target after using the maximum tolerated dose of statin therapy, or when treatment outcomes are suboptimal due to poor compliance or other factors, inclisiran can serve as an effective adjunct for enhanced lipid lowering [32].

ADVERSE CARDIOVASCULAR EVENTS:

Based on 3 phase III clinical trials (ORION-9, ORION-10, and ORION-11), a total of 3655 individual participants (inclisiran [n=1833]; placebo [n=1822]) at high risk for cardiovascular events were included. The data were analyzed to assess the relationship between inclisiran and the risk of adverse cardiovascular events. The occurrence of major adverse cardiovascular events (MACE), as well as fatal and nonfatal myocardial infarction and fatal and nonfatal stroke, was reported. The results indicated that the inclisiran group experienced significantly fewer MACEs than the placebo group (131 cases vs 172 cases) [33]. At Day 540, Kaplan-Meier estimates indicated the rates of MACEs, fatal and nonfatal myocardial infarction, and fatal and nonfatal stroke were 7.4% vs 9.5% and 1.9% vs 2% for the inclisiran and placebo treatment groups, respectively. The rates for fatal and nonfatal stroke were 3% and 0.7% vs 0.9%. Cox proportional hazards regression analysis revealed that inclisiran, compared with placebo, had hazard ratios of 0.75 (95% CI: 0.60, 0.94) for MACEs, 0.81 (95% CI: 0.51, 1.29) for fatal and nonfatal myocardial infarction, and 0.81 (95% CI: 0.51, 1.29) for death. The hazard ratio for fatal and nonfatal stroke was 0.80 (95% CI: 0.39, 1.67). These findings confirm that early treatment with inclisiran can significantly reduce the incidence of MACE in patients at high risk for cardiovascular events, thereby enhancing patient prognosis and quality of life. However, the duration of outcome observation is limited, and further long-term clinical observational research is necessary for supplementary verification of MACE outcomes.

POPULATION STUDIES IN INCLISIRAN:

According to the high-frequency keyword table and keyword time series analysis chart, prior to 2020 (Figures 2, 3), research on inclisiran predominantly focused on verifying its efficacy and safety. After 2020, the research objectives have gradually become more refined, indicating that the overall effectiveness and safety of the drug have been largely established. The current and future trend is expected to involve more personalized group studies on patients, including evaluations of inclisiran across different races or demographic groups. The ORION-15 study specifically assessed the efficacy, safety, and pharmacokinetics of inclisiran in Japanese patients with high-risk cardiovascular disease and elevated LDL-C levels. The results indicated that over 86% of patients treated with inclisiran achieved the lipid management goals established by the Japanese Atherosclerosis Society in 2017 [34]. In terms of pharmacokinetics, inclisiran was undetectable in plasma after 48 h across all doses. Its safety profile aligns with findings from long-term global studies of inclisiran [19]. Additionally, ORION-18 represents the first phase III double-blind trial conducted in China, primarily evaluating the efficacy and safety of inclisiran in patients with ASCVD or those at high risk for ASCVD. Therefore, inclisiran is demonstrated to be safe and effective in Asian patients with ASCVD or high-risk ASCVD [35]. Future research will further validate the conclusions drawn from studies involving diverse patient groups.

Evidence from epidemiological, genetic, and clinical studies indicates that LDL-C is a significant risk factor for ASCVD. Specifically, for every 1 mmol/L decrease in LDL-C, the incidence of ASCVD events is reduced by 20% to 23%. Furthermore, data indicate that since the 20th century, the overall mortality rate from coronary heart disease in the United States has exhibited a downward trend, with risk factor control contributing 44% and reductions in total cholesterol accounting for 24% of this decline. Consequently, most countries and regions consider patients with hypercholesterolemia as the primary treatment target among those with dyslipidemia [29]. The study of inclisiran in patients with homozygous familial hypercholesterolemia (HoFH), known as the ORION-2 study, demonstrated that when combined with statins and ezetimibe, inclisiran effectively reduces LDL-C levels in HoFH patients [36]. The ORION-9 study involved 482 adults with HeFH and found that inclisiran significantly reduced LDL-C levels in patients across all HeFH genotypes. The incidence of adverse events was comparable between the 2 groups, suggesting that inclisiran offers a safe and effective treatment option for patients with hypercholesterolemia [37].

APPLICATION IN THE ONCOLOGY FIELD:

PCSK9 inhibitors and PCSK9 siRNA have been extensively investigated in the context of cancer research. Several studies indicate that PCSK9 is highly expressed in various tumor tissues [38]. The overexpression of PCSK9 can influence epithelial-mesenchymal transition and phosphatidylinositol 3-kinase signaling in tumor cells [39]. The kinase/protein kinase B signaling pathway is known to enhance the proliferation, migration, and invasion of tumor cells [40]. Additionally, PCSK9 siRNA has been shown to promote apoptosis in tumor cells via mitochondrial and endoplasmic reticulum pathways. In vitro experiments further demonstrate that PCSK9 siRNA can protect prostate cancer cells from radiation-induced damage by inhibiting apoptosis, suggesting that inclisiran has potential applications in cancer treatment [41].

Discussion

Inclisiran is a promising siRNA that inhibits the production of PCSK9 in liver cells, resulting in reduced degradation of low-density LDLR and thereby lowering LDL-C levels. It requires only 2 to 3 injections per year [42]. In the United States, inclisiran is FDA-approved as an adjunct to the highest tolerated statin therapy, with or without additional lipid-lowering treatments, for patients who are statin intolerant or contraindicated for statin use. When combined with lipid-lowering therapy, LDL-C levels can be reduced by 44% to 54% in patients with ASCVD or those at high risk of developing hypercholesterolemia [43–45]. Inclisiran is recommended for secondary prevention in patients with ACVD who are statin intolerant or require additional LDL-C lowering [46]. However, ezetimibe remains a more suitable option for primary prevention of ASCVD and for patients needing to reduce residual LDL-C levels, due to its lower cost and potential to improve cardiovascular outcomes [47]. Inclisiran has demonstrated efficacy in treating individuals at high risk for ASCVD as well as those with HeFH [48]. Strict management of patients’ blood lipid levels has significantly decreased the risk of cardiovascular events, alleviated economic burdens, and improved the overall quality of life for patients [49]. For patients with diabetes and mild hepatic hyperlipidemia who also present with renal impairment, the treatment dose and individualized regimen for inclisiran do not require modification. While the reduction in PCSK9 and LDL-C levels in patients with moderate liver damage is somewhat less pronounced than in those with normal or mild liver damage, this variance does not necessitate an adjustment in the treatment dosage. Some studies indicate that the long-term use of statin lipid-lowering agents can pose potential risks for liver function impairment and can lead to negative emotional outcomes, such as anxiety and depression, which significantly reduce treatment compliance [50]. In severe cases, sleep quality can also be adversely affected. Furthermore, chronic mood disorders and lifestyle disturbances can negatively impact the recovery of patients from physical ailments [51]. In contrast to traditional statin lipid-lowering drugs, inclisiran exerts a reduced burden on liver and kidney function [52]. However, research has yet to confirm whether it can indirectly enhance treatment outcomes by alleviating patients’ concerns and mitigating negative emotions. Although inclisiran demonstrates a weaker capacity to lower LDL-C than do PCSK9 monoclonal antibodies, its biannual dosing schedule is significantly less frequent than the bi-monthly regimen of monoclonal antibodies, making it more acceptable to patients [53]. Frequent administration of monoclonal antibodies and the prevalence of injection site adverse reactions have imposed a significant psychological burden on patients undergoing long-term treatment. A survey on the use of PCSK9 monoclonal antibodies indicated that 33.7% of patients discontinue treatment due to its high cost [54]. In contrast, the targeted specificity of inclisiran results in minimal efficacy variation among individuals, while its lipid-lowering effect is long-lasting and stable. Additionally, its method of administration is more convenient, mitigating fluctuations in patients’ blood lipid levels caused by various factors. This reduction in fluctuations lowers the risk of ASCVD and enhances patients’ prognosis and quality of life. Inclisiran is also characterized by good safety and tolerability [55]. Multiple clinical trials have established that inclisiran presents a low risk of adverse events, primarily limited to injection site reactions. To date, no serious adverse events have been reported [56,57].

Regarding the long-term effectiveness, safety, and cardiovascular outcomes of inclisiran, the earliest cohort of subjects has been monitored for approximately 8 years. Further and longer-term follow-up studies are necessary to evaluate its impact on the prevention and treatment of cardiovascular diseases. Additionally, the molecular mechanisms and pathways through which inclisiran-mediated reduction of LDL-C exerts cardiovascular protective effects remain to be elucidated. The development of new siRNA drugs targeting other lipid metabolism or cardiovascular disease-related genes may offer opportunities for personalized and precision medicine. The highly controlled nature of clinical trials often fails to reflect the complexities and diversity present in clinical practice. For instance, the populations included in current clinical trials predominantly consist of white males, highlighting the need for more comprehensive research to confirm the long-term efficacy and safety of inclisiran across various racial, ethnic, and social groups. Previous studies have demonstrated that lower LDL-C levels can significantly reduce the risk of cardiovascular events and mortality in patients with dyslipidemia [58,59]. The latest blood lipid management guidelines propose more stringent requirements for blood lipid control. While it is essential to maintain low blood lipid levels, it is equally important to avoid significant fluctuations in these levels. This indicates that the advantages of long-term, stable blood lipid control far outweigh those of short-term, fluctuating control [6]. Consequently, future research should prioritize the long-term efficacy, safety, and cardiovascular outcomes associated with inclisiran. Ongoing studies such as ORION-4, ORION-1, and ORION-2 aim to establish the long-term safety of inclisiran in patients who are at high cardiovascular risk and have elevated LDL-C. The results of the ORION-4 study are not anticipated to be announced until 2026, and its primary endpoint is the incidence of MACEs. In the ORION 9, 10, and 11 clinical studies, research conducted by Ray et al indicated that inclisiran significantly reduced the prevalence of MACEs; however, the effect of inclisiran on MACE reduction remains uncertain [60].

According to a survey report on dyslipidemia in Chinese adults, the overall prevalence of dyslipidemia among adults is as high as 35.6%, while the lipid-lowering treatment coverage rate for patients at high-risk for ASCVD is only 5.5%, and the LDL-C target achievement rate stands at just 25.5%. Dyslipidemia has become a significant threat to public health [61]. The low treatment coverage can be attributed primarily to issues related to treatment cost, convenience, and efficacy, which directly impact patient compliance. Addressing these concerns by providing cost-effective solutions, enhancing treatment accessibility, and reducing economic burdens can significantly improve patient adherence. The development of inclisiran aims to address the limitations of traditional lipid-lowering drugs. However, reducing production costs and improving manufacturing efficiency remain key challenges for developers. Currently, the price of inclisiran in the United States (2023) is $3,290.63 per dose, with actual patient expenses varying based on insurance type and coverage. Notably, inclisiran is not covered by insurance in China, further exacerbating the financial burden on patients. Despite its potential for improved therapeutic benefits and prognostic outcomes, the high cost of treatment remains a deterrent. If production costs can be reduced, inclisiran may gain wider acceptance and potentially become a first-line lipid-lowering therapy [62], offering promising prospects for effective management of dyslipidemia [63].

Angiopoietin-like 3 (ANGPTL3) and PCSK9 are prominent targets in contemporary lipid-lowering research. Zodasiran (Levodasilan), a novel drug with significant potential for targeting ANGPTL3, represents the siRNA lipid-lowering therapeutic drug, following inclisiran, specifically targeting ANGPTL3 in the liver. The clinical development of zodasiran has advanced to phase II trials, focusing on mixed hyperlipidemia and exploring its effects on ANGPTL3 deficiency and the risk of hepatic steatosis [64]. The emergence of siRNA-based lipid-lowering drugs signifies a new era in lipid management, transitioning therapy into the realm of RNA therapeutics. Additionally, this approach holds untapped potential in other fields, such as cancer therapy, which is anticipated to be further validated through ongoing and future studies.

Conclusions

In conclusion, inclisiran, as a promising new lipid-lowering agent, will provide a new optimal therapeutic strategy for patients with hyperlipidemia, as the lipid-lowering study of inclisiran continues to improve.