Innovations of Diagnosis and Treatment of Coronary Artery Disease

1. Introduction

Coronary artery disease (CAD) is the leading cause of death worldwide, responsible for over 19.2 million deaths in 2023 and one in three global fatalities.[1] Innovations in diagnosis and management have significantly improved outcomes; however, the burden persists, especially in low-resource settings.

CAD, resulting from occlusion of the coronary arteries and causing a demand-supply mismatch of oxygen, can lead to severe complications such as acute coronary syndrome and heart failure.[2] Despite significant progress in prevention and treatment, the global burden of CAD continues to rise, highlighting the need for advancements in diagnostic, interventional, and therapeutic strategies.[3]

Dyslipidaemia, hypertension, obesity, smoking, diabetes, genetics, immune responses, and infections can increase the risk of developing CAD. These conditions contribute to the gradual buildup of plaque in the arteries.[4] Many personal factors affect how individuals respond to CAD treatment. Using a tailored approach based on individual risks—like bleeding or ischemia—can lead to better outcomes, but choosing the proper treatment for each person is still a challenge.[5] Risk stratification is essential for guiding treatment decisions in both acute and chronic cases of the disease. A range of invasive and non-invasive methods can be used to tailor care based on individual patient profiles.[5]

This review brings together the most recent developments in CAD management, with an emphasis on three primary areas: advancements in diagnostics, progress in interventional cardiology, and breakthroughs in pharmacological therapy.

Despite these advancements, several critical challenges remain unaddressed in CAD management, including the need for validated biomarkers and imaging modalities to identify vulnerable atheroma before symptoms arise.[5]

2. Methods

This narrative review provides a comprehensive overview of recent advancements in the diagnosis, intervention, and pharmacological management of CAD, with a focus on emerging technologies shaping its future. A narrative review approach was employed to integrate evidence from diverse sources, including clinical trials, systematic reviews, meta-analyses, and preclinical studies, to provide a comprehensive overview of the current landscape and emerging trends in CAD management. This review is structured around four key domains —diagnostic innovations, advances in interventional cardiology, pharmacological breakthroughs, and future directions —that reflect the multifaceted evolution of CAD care.

The literature included in this review was sourced from original research articles and review papers published between January 2010 and December 2025. These references were identified through systematic literature search on PubMed, Scopus, Google Scholar, and institutional websites (e.g., The University of Edinburgh), using keywords such as "coronary artery disease," "CT angiography," "artificial intelligence," "fractional flow reserve," "high-sensitivity troponin," "lipoprotein(a)," "drug-eluting stents," "robotic PCI," "SGLT2 inhibitors," "nanomedicine," "3D bioprinting,” " lipid-lowering agents, " and " drug-coated balloons.” Case reports, series, and editorials were excluded.

Figure 1. Subtopics under the advancement in coronary artery disease.

Figure 1. Subtopics under the advancement in coronary artery disease.

3. Diagnostic Innovations

3.1. Advanced Imaging Techniques

3.1.1. High-Resolution CT Angiography and AI-Driven Analysis for Early Plaque Detection

High-resolution coronary computerised tomography coronary angiography (CTCA), enabled by multidetector CT scanners, provides detailed imaging of the heart and coronary arteries, making it a class 1, evidence level A tool for detecting CAD.[6] While effective in identifying coronary calcium, plaque, and stenosis significance, its labour-intensive nature and demands highly skilled experts for image interpretation limit accessibility.[7] Advances in artificial intelligence (AI), particularly deep learning, enhance CTCA by accelerating analysis, detecting high-risk plaque features, and enabling precise risk stratification.[8] AI also supports longitudinal studies on plaque progression and treatment efficacy, advancing personalised CAD management.[8] This integration promises improved early detection, diagnosis, and patient outcomes.[8]

3.1.2. Non-Invasive Fractional Flow Reserve (FFR-CT) to Assess Blood Flow

FFR-CT is a computational post-processing technique that is applied to standard CT (CTCA) images. It employs artificial intelligence and computational fluid dynamics (CFD) to analyse hemodynamic parameters, aiding in the identification of ischemia-inducing coronary lesions. Unlike traditional CTCA, which provides only anatomical details, FFR-CT adds a functional perspective, enhancing diagnostic accuracy. By combining FFR-CT with plaque characterisation, clinicians can better stratify patient risk and make informed treatment decisions.[9,10,11,12]

FFR-CT can effectively minimise unnecessary invasive procedures, thereby reducing the potential complications associated with them. Specifically, individuals with FFR-CT values exceeding 0.80 generally exhibit results similar to those without substantial coronary artery disease. Integrating FFR-CT into diagnostic workflows also contributes to lower healthcare expenses, mainly by reducing the need for invasive angiography. For example, data from the PLATFORM trial show that using CTCA combined with FFR-CT can substantially reduce costs in comparison to traditional approaches relying on immediate ICA.[9,13]

Despite the ongoing advancements in FFR-CT technology, including improved AI models and real-time analysis, challenges such as image quality dependency, computational demands, and the need for widespread clinical validation remain. Further research is needed to expand its applicability to more complex cases, such as multi-vessel disease and in-stent restenosis assessment.[14]

3.2. Biomarkers

3.2.1. High-Sensitivity Troponin Assays for Early Detection of Myocardial Injury

High-sensitivity cardiac troponin (hs-cTn) assays have revolutionised the early detection of myocardial injury, particularly in diagnosing acute myocardial infarction (AMI). These assays enable the measurement of very low concentrations of cardiac troponins, allowing for the identification of minor myocardial injuries that were previously undetectable with conventional assays.[15]

The primary advantage of hs-cTn assays lies in their ability to rapidly and accurately rule out AMI in patients with chest pain. Studies have demonstrated that a single hs-cTn measurement at presentation, with thresholds near the assay's limit of detection, can effectively exclude AMI. For instance, a systematic review highlighted that a single test at presentation using a threshold at or near the assay limit of detection could reliably rule out non-ST-segment elevation myocardial infarction (NSTEMI) for various hs-cTn assays.[15]

Moreover, serial hs-cTn measurements enhance diagnostic accuracy by detecting dynamic changes in troponin levels and distinguishing acute from chronic myocardial injury. This approach is particularly beneficial for patients presenting early after symptom onset, as initial troponin values may be normal owing to the time dependency of troponin release. A meta-analysis indicated that serial measurement strategies are necessary in early presenters to overcome the troponin-blind period typically seen in the early hours of AMI.[16]

Due to the increased sensitivity, troponin elevations can be observed in a broader range of conditions, including type 1 myocardial infarction, heart failure, chronic kidney disease, cardiac arrhythmias, myocarditis, sepsis and other cardiac and non-cardiac conditions. It is crucial to interpret troponin results within the context of the patient’s clinical presentation, including symptoms and ECG findings. Serial troponin sampling is essential not only to permit the safe rule-out of myocardial infarction but also to minimise the risk of misdiagnosis in patients with elevated cardiac troponin concentrations.[17,18]

3.2.2. Interleukin-6 (IL-6)

Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a crucial role in immune response and inflammation. IL-6 is involved in the activation of acute-phase proteins, such as C-reactive protein (CRP), and has been shown to promote endothelial dysfunction, which is a critical step in the development of atherosclerosis.[19]

Elevated IL-6 levels have been consistently associated with an increased cardiovascular risk, including higher rates of myocardial infarction, stroke, and heart failure. For instance, a narrative review summarising data from prospective studies found that higher IL-6 levels correlate with adverse cardiovascular outcomes across diverse populations.[19]

The relationship between IL-6 and CAD severity has also been explored using angiographic assessments. A study stratified by IL-6 levels in patients with CAD found that higher IL-6 levels are associated with greater disease severity, as indicated by higher Gensini scores and more extensive arterial involvement. This finding underscores IL-6’s role as a predictor of CAD progression.[20]

3.2.3. Lipoprotein [Lp(a)]

Lipoprotein (Lp [a] ) is a lipoprotein variant consisting of an LDL-like particle attached to a specific protein called apolipoprotein(a). Lp(a) is an independent risk factor for cardiovascular diseases, particularly CAD. Unlike other lipoproteins, Lp(a) levels are primarily determined by genetics and remain relatively stable throughout an individual’s life.[21,22]

Lp(a) has been shown to promote atherogenesis through several mechanisms, including inhibition of fibrinolysis, endothelial dysfunction, and increased arterial wall cholesterol deposition. Elevated Lp(a) levels have been linked to an increased risk of CAD, particularly in individuals who have a family history of premature cardiovascular disease.[21]

Lp(a) is associated with coronary artery calcification, a marker of atherosclerotic burden. Research indicates that elevated Lp(a) levels are associated with increased coronary artery calcification, suggesting a role in plaque development and stability.

Longitudinal studies have demonstrated that elevated Lp(a) levels predict plaque progression in patients with CAD. This finding highlights the potential of Lp(a) as a biomarker for monitoring disease progression and tailoring therapeutic strategies.[23]

A subsequent analysis revealed that elevated Lp(a) concentrations exceeding 100 mg/dL were independently associated with an increased risk of severe degenerative aortic stenosis and the subsequent need for aortic valve replacement, irrespective of the initial severity of stenosis.[24]

In summary, accumulating evidence positions IL-6 and Lp(a) as crucial markers for predicting CAD progression. Their measurement could enhance risk stratification and inform personalised treatment strategies. Ongoing research is essential to fully elucidate their roles and develop targeted interventions to mitigate their pro-atherogenic effects.

4. Advances in Interventional Cardiology for Coronary Artery Disease

The evolution of interventional cardiology has significantly improved the management of CAD, which is one of the leading causes of morbidity and mortality worldwide. This review focuses on three pivotal areas: drug-coated balloons, drug-eluting stents (DES), and robot-assisted percutaneous coronary intervention (PCI). These technologies address complex clinical challenges and enhance outcomes for CAD patients by enabling precision, ensuring safety, and reducing complication rates.[25]

4.1. Drug-Coated Balloons in CAD Management

Drug-coated balloons (DCBs) are a promising therapeutic modality for the management of CAD, providing targeted pharmacological intervention without the need for permanent vascular scaffold placement. Originally designed to address in-stent restenosis (ISR), their utility has expanded to include small-calibre vessels and bifurcation lesions, where conventional stenting may pose technical or long-term challenges.[26,27]

4.1.1. DCBs for ISR

ISR remains the most well-established indication for DCB therapy, primarily because it allows avoiding the use of multiple metallic stent layers. Among the available technologies, paclitaxel-coated balloons have undergone extensive evaluation in randomised controlled trials and now serve as the standard for emerging DCB platforms. Comparative studies have consistently demonstrated the superiority of DCBs over conventional balloon angioplasty for ISR management, with notable reductions in luminal narrowing and the need for repeat revascularisation procedures.[27,28,29]

4.1.2. DCB in Denovo Lesion

Early comparisons between DCBs and DES for de novo small vessel lesions, such as in the PICOLETTO trial, revealed limitations of first-generation DCBs. It was primarily due to suboptimal drug delivery and inadequate vessel preparation.[30] However, subsequent randomised trials using improved paclitaxel-coated balloons demonstrated noninferiority to DES, supporting a DCB-only strategy in select cases.[31,32]

4.1.3. Future of DCBs

Bifurcation lesions pose procedural challenges and are associated with suboptimal long-term outcomes, making drug-coated balloons (DCBs) in the side branches an attractive alternative to conventional angioplasty. While observational data suggest improved patency and safety at 12 months, randomised trials remain limited and mixed in outcomes.[33,34]

In addition to bifurcations, DCBs may offer distinct advantages in specific populations. Their scaffold-free design reduces vessel trauma and may lower the risk of thrombosis, potentially shortening the duration of dual antiplatelet therapy. This is particularly beneficial for patients at high risk of bleeding.[35] DCBs hold particular promise in patients with diabetes, where coronary disease tends to diffuse with longer lesions and DES underperforms with a higher incidence of ISR. DCBs may allow for shorter stented segments but longer areas of treatment, with the option of bail-out stenting if required, thereby decreasing the risk of restenosis.[27]

4.2. Drug-Eluting Stents in CAD Management

4.2.1. Historical Context

Bare-metal stents (BMS) were the first breakthrough in CAD treatment, reducing acute vessel recoil and restenosis rates. However, the limitations of BMS, including high rates of in-stent restenosis (up to 30%), led to the development of DES. These stents combine a metallic scaffold, a polymer coating, and an antiproliferative drug to prevent neointimal hyperplasia. [36]

4.2.2. Modern Innovations

• Thinner Strut Designs

Contemporary DES are engineered with ultrathin struts, typically below 80 microns, enhancing deliverability through tortuous vessels, minimising vessel trauma, and accelerating endothelial healing. At the same time, clinical studies highlight their improved outcomes in patients with complex anatomies, including bifurcations and calcified lesions.[37]

2.

Biodegradable Polymers

Bioresorbable polymer coatings in drug-eluting stents, such as the Orsiro DES and Synergy stent, release their therapeutic drug over a predetermined period before degrading, leaving a bare-metal scaffold that reduces the long-term risk of late stent thrombosis.[38,39]

3.

Polymer-Free Stents

The BioFreedom stent exemplifies an innovative approach to stent design by employing microporous or nanoporous surfaces for drug delivery, eliminating the need for a polymer coating and thereby addressing concerns about polymer-induced inflammation and hypersensitivity.[40]

4.

Advanced Drugs

Antiproliferative Agents: Modern DES employ sirolimus analogues such as everolimus, zotarolimus, and biolimus, which are more effective and better tolerated than earlier agents, such as paclitaxel.[39]

4.2.3. Clinical Benefits

DES have significantly reduced restenosis rates to 2–10%, compared to 30% with BMS. At the same time, biodegradable polymers lower the risk of late thrombosis, and faster endothelial coverage shortens the required duration of dual antiplatelet therapy, offering particular benefits for patients at high bleeding risk.[39,41]

4.2.4. Challenges

Neoatherosclerosis, characterised by the development of new atherosclerotic plaques within the stent, poses a challenge for advanced DES, which, despite their benefits, are more expensive and thus less accessible in specific healthcare settings. At the same time, research continues to explore personalised approaches to stent selection.[42]

4.3. Robotic-Assisted Percutaneous Coronary Intervention

Robotic percutaneous coronary intervention (R-PCI) is an innovative method for PCI, enabling operators to remotely manipulate guidewires and catheter devices via advanced, precision-controlled technology.[10,43]

4.3.1. Key Features

• Precision and Stability

Robotic systems, such as the CorPath GRX, provide sub-millimetre accuracy, essential for navigating complex lesions, including bifurcations and chronic total occlusions, enabling precise stent and balloon placement.[43,44]

2.

Radiation Protection

Operators work from a shielded console, minimising radiation exposure and alleviating the need for heavy lead aprons.[10,44,45,46]

3.

Remote Operation (Tele-Stenting)

When controlled remotely, robotic systems enable the expansion of advanced treatment capabilities to underserved regions. For instance, proof-of-concept trials have demonstrated the success of tele-stenting procedures, showcasing the potential of this technology to revolutionise access to specialised care.[47]

4.3.2 Clinical and Operator Benefits

Improved procedural accuracy, achieved through enhanced precision, minimises complications, such as malposition and edge dissection. This advancement has led to higher success rates, particularly in cases involving high-risk or anatomically challenging lesions. [43]Furthermore, operator ergonomics are significantly improved, reducing physical strain and occupational hazards, which contribute to a safer and more efficient procedural environment. [47]

Challenges

The adoption of robotic systems is hindered by their high cost, which makes them less accessible in low-resource settings. Additionally, their practical use requires extensive training and experience to achieve optimal outcomes. Current robotic systems also face limitations when addressing complex cases, such as multi-vessel disease and highly tortuous anatomies, further restricting their application in specific scenarios.[48]

4.4. Shielding Systems for Radiation Protection

Interventional cardiology procedures expose medical personnel to significant ionising radiation, leading to occupational health risks such as cataracts, thyroid disorders, and musculoskeletal issues from heavy lead aprons.[49,50] To address these concerns, advanced fixed shielding systems have emerged as vital innovations. These systems create a protective barrier between the operator and the radiation source, aligning with the "As Low As Reasonably Achievable" (ALARA) principle and facilitating a shift towards a "lead-free" environment in cardiac catheterisation laboratories by minimising the reliance on traditional personal protective equipment.[49]

Innovations in fixed shielding include comprehensive integrated systems, such as the Protego radiation shielding system (Image Diagnostics Inc.), and suspended-body shielding units, such as the Zero-Gravity system (BIOTRONIK). The Protego system features an angulated upper shield, a lower shield, accessory side shields, flexible drapes with vascular access portals, and specialised arm boards, all designed to allow unimpeded C-arm motion while providing superior protection against radiation exposure.[50] The Zero-Gravity system, a 1-mm lead body shield suspended from the floor or ceiling, effectively reduces operator radiation exposure and alleviates the orthopaedic strain associated with lead aprons.[49]

The adoption of these fixed shielding systems offers substantial benefits, including enhanced and consistent radiation protection and significantly reduced operator radiation exposure, well below recommended safety limits. They also mitigate the orthopaedic burden on interventional cardiologists, improving comfort, focus, and career longevity. These technologies represent a critical advancement in occupational radiation safety within interventional cardiology, ultimately benefiting both medical staff and patients.[49,50]

5. Pharmacological Breakthroughs

5.1. Lipoprotein(a) Reduction

Elevated lipoprotein (a) [Lp (a)] levels are an independent risk factor for CAD. Muvalaplin demonstrated a reduction in lipoprotein(a) levels, as assessed through both intact lipoprotein(a) and apolipoprotein(a)-based assays, while exhibiting good tolerability. Further studies are required to evaluate their impact on cardiovascular outcomes.[51]

Furthermore, Evolocumab effectively lowers lipoprotein(a) levels, with patients who start with higher levels showing larger drops and gaining more heart-related benefits from PCSK9 inhibitor treatment.[52]

5.2. Anti-Inflammatory Therapies

Chronic inflammation plays a pivotal role in atherosclerosis and subsequent cardiovascular events. The CANTOS trial investigated canakinumab, an IL-1β inhibitor, and revealed that targeting inflammation without affecting cholesterol levels can significantly reduce recurrent cardiovascular events. This approach represents a transformative change in CAD management, focusing on the inflammatory component of the disease.[53,54]

5.3. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors

Initially developed for the management of type 2 diabetes, SGLT2 inhibitors have shown cardiovascular benefits. [55] Sotagliflozin (Inpefa), a novel SGLT inhibitor, demonstrated a 23% reduction in heart attacks, strokes, and cardiovascular-related deaths compared to placebo. This positions sotagliflozin as a multifaceted therapeutic agent addressing interconnected health issues such as heart failure and diabetes.[56]

Among the available SGLT2 inhibitors, dapagliflozin has emerged as a cornerstone therapy for cardiovascular care. The DAPA-HF trial established dapagliflozin’s efficacy in reducing the risk of worsening heart failure and cardiovascular death in patients with reduced ejection fraction, regardless of diabetes status.[57] More recently, the DAPA-MI trial evaluated dapagliflozin in patients with acute myocardial infarction without prior diabetes or chronic heart failure. The study demonstrated improved cardiometabolic outcomes, including reduced incidence of new-onset type 2 diabetes and favourable weight reduction. However, it did not show a statistically significant reduction in major adverse cardiovascular events compared to placebo.[58]

5.4. New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk

Advancements in lipid-lowering therapies beyond traditional statins for managing coronary artery disease (CAD), like proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (evolocumab and alirocumab), which effectively reduce LDL cholesterol levels and lower cardiovascular risk, particularly in patients intolerant to statins. [59,60]Another breakthrough is inclisiran, an siRNA-based therapy that provides sustained LDL reduction with biannual dosing, enhancing patient adherence.[60] In a recent meta-analysis, inclisiran was shown to substantially reduce total cholesterol, ApoB, and non-HDL-C, respectively, by 37%, 41%, and 45%.[61]

6. Future Directions & Challenges

Atherosclerosis, a leading cause of heart attacks and strokes, is primarily driven by hypercholesterolemia and chronic inflammation within arterial walls.[3] Although statins and other standard therapies can slow disease progression, they often come with limitations such as side effects, high costs, and an inability to reverse established plaques.[62] In advanced cases, surgical interventions like coronary artery bypass grafting (CABG) are necessary, yet these procedures face significant hurdles, including limited graft availability and complications related to surgical trauma.[63] Given these challenges, innovative approaches such as nanomedicine and 3D bioprinting have emerged as promising alternatives for improving cardiovascular treatment.

6.1. Advancements in Nanomedicine

Nanomedicine, which utilises nanoparticles and nanocarriers to deliver drugs directly to atherosclerotic plaques, is revolutionising the management of cardiovascular disease.[64]These nanoparticles can be engineered to target inflamed arterial sites, increasing drug accumulation in plaques while minimising off-target effects.[65]

Cholesterol clearance is a promising application of nanomedicine. Supramolecular nanotherapy has demonstrated the ability to dissolve cholesterol crystals, reducing plaque burden in preclinical studies.[65] Additionally, nanoparticles designed to inhibit macrophage-driven inflammation have been shown to stabilise plaques by blocking inflammatory signals. [66] Beyond plaque reduction, some nanosystems also facilitate vascular repair by restoring endothelial function, stabilising vessel walls, and preventing further narrowing of arteries.[67]

Although these advancements are promising, translating nanomedicine from preclinical models to clinical applications remains challenging. Although lipid nanoparticle-based cholesterol efflux therapies have demonstrated efficacy in laboratory studies, only a few nanomedicine treatments have progressed to human trials.[68] Further research is needed to refine nanoparticle formulations, improve targeting precision, and ensure safety before widespread clinical adoption.[68,69]

6.2. 3D-Printed Artificial Blood Vessels

In addition to nanomedicine, 3D bioprinting is emerging as a revolutionary technology in cardiovascular surgery. Researchers at the University of Edinburgh have developed a novel 3D bioprinting technique to fabricate artificial blood vessels that mimic natural veins.[70] The process involves printing a tubular gelatin hydrogel on a rotating spindle, followed by electrospinning an ultrathin biodegradable polyester nanofiber coating to enhance mechanical strength.[71]

These 3D-printed vascular grafts offer several advantages over conventional grafts. By eliminating the need for vein harvesting, they reduce surgical trauma, post-operative pain, and the risk of infection.[70,71] Additionally, they are designed to be more biocompatible than synthetic small-diameter grafts, which often fail due to poor integration and thrombosis. [71,72] Future iterations of these grafts may incorporate patient-derived cells, creating living vessels that promote long-term integration and function.[72]

Despite their potential, 3D-printed blood vessels remain in the preclinical stages. Ongoing studies are evaluating their durability, patency, and integration with native tissue in animal models. Before they can be used widely in cardiovascular surgery, large-scale human trials will be necessary to confirm their safety and efficacy.[72]

6.3. Clinical Implications and Future Directions

Emerging technologies such as nanomedicine and 3D bioprinting have the potential to enhance current cardiovascular treatment strategies significantly. Targeted nanoparticle therapies have the potential to stabilise or shrink plaques, potentially reducing the need for invasive procedures. [73] Meanwhile, customised 3D-printed grafts may serve as durable and biocompatible replacements for diseased blood vessels, addressing a long-standing challenge in CABG surgery.[70,71,72]

However, several hurdles remain before these technologies can be fully integrated into clinical practices. For nanomedicine, concerns about safety, scalability, and regulatory approval must be addressed.[69] Similarly, for 3D-printed blood vessels, extensive testing in human trials is required to establish long-term outcomes and reliability.[73]

As research progresses, these advancements in nanomedicine and 3D bioprinting are expected to revolutionise cardiovascular therapy, offering new hope to patients with atherosclerosis and other vascular diseases.

7. Discussion

Despite significant advancements in the diagnosis, intervention, and pharmacological treatment of coronary artery disease (CAD), several challenges continue to hinder optimal patient outcomes clinically and economically.

Clinically, current care pathways remain heavily focused on late-stage ischemia and obstructive lesions, often overlooking the early detection of subclinical atheroma. This reactive model delays intervention until irreversible myocardial damage has occurred. Although emerging imaging modalities and biomarkers offer promise for earlier diagnosis, their routine implementation remains limited by cost, availability, and guideline inertia.

From the economic prospective, the burden of CAD is profound. In 2023, global healthcare spending on cardiovascular disease exceeded $1 trillion, with CAD accounting for a substantial proportion of direct and indirect costs.[74] Hospitalizations, long-term pharmacotherapy, and productivity losses due to disability contribute to this financial strain. Investment in early detection and population-based prevention strategies could hold substantial long-term savings and reduce reliance on high-cost interventions.

8. Conclusion

While technological and therapeutic advances have reshaped the landscape of CAD management, addressing these persistent clinical, economic, and accessibility challenges is vital to reducing the global burden of disease. Future efforts must prioritize early detection, equitable access, and cost-effective, personalized care to achieve sustainable improvements in cardiovascular outcomes.