European Journal of Cardiovascular Medicine

Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide, contributing significantly to the global burden of cardiovascular illness (1). It is characterized by the progressive narrowing and obstruction of coronary arteries due to atherosclerosis, resulting in impaired myocardial blood flow and an increased risk of ischemic events such as angina and myocardial infarction (1,2). Over the past few decades, advances in both pharmacological and interventional cardiology have transformed the management of CAD, shifting the focus from mere symptom control to risk modification, prevention of progression, and improvement in long-term survival (3,4).

Historically, the mainstay of CAD management was lifestyle modification and pharmacotherapy, particularly the use of lipid-lowering agents (5). Statins, introduced in the late 20th century, revolutionized the medical management of CAD by effectively lowering low-density lipoprotein cholesterol (LDL-C), stabilizing atherosclerotic plaques, and reducing cardiovascular morbidity and mortality (6,7). Their pleiotropic effects, such as anti-inflammatory and endothelial stabilizing properties, have further enhanced their role as cornerstone agents in both primary and secondary prevention of CAD (8, 9). Despite their widespread use and proven benefits, statins alone are often insufficient in halting disease progression in patients with advanced or symptomatic CAD, necessitating the use of additional therapeutic strategies (10, 11).

The development of percutaneous coronary interventions (PCI) represented a paradigm shift in CAD management (12, 13). Balloon angioplasty provided the first breakthrough in mechanically restoring coronary patency, but high rates of restenosis limited its effectiveness (14, 15). This limitation was overcome by the advent of bare-metal stents, which significantly reduced vessel recoil and improved procedural outcomes (16). However, restenosis due to neo-intimal hyperplasia remained a challenge (17). The introduction of drug-eluting stents (DES), capable of locally delivering anti-proliferative agents, marked another milestone in the interventional era, reducing restenosis rates and improving long-term vessel patency (18,19). Today, advances in stent technology, including biodegradable scaffolds and newer-generation DES, have further refined interventional outcomes, with ongoing trials evaluating long-term safety and efficacy (20).

Contemporary management of CAD therefore reflects a dual strategy—comprehensive pharmacological therapy alongside interventional techniques (21). In addition to statins, newer lipid-lowering therapies such as PCSK9 inhibitors and ezetimibe have broadened the pharmacological armamentarium (22, 23). On the interventional side, advancements in imaging modalities such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have improved lesion assessment and stent deployment, further optimizing clinical outcomes (24). The integration of pharmacology and intervention has become increasingly patient-centered, with strategies tailored based on disease severity, comorbidities, and individual risk profiles (25, 26).

Given the rapidly evolving landscape, there is a need to synthesize available evidence on the comparative and complementary roles of medical therapy and interventional strategies in CAD. This systematic review aims to explore the continuum from statins to stents, highlighting technological enhancements, clinical outcomes, and current consensus in contemporary CAD management. By evaluating both pharmacological and interventional advancements, this review seeks to provide a comprehensive perspective on the optimal integration of these strategies for improving patient care and long-term prognosis in CAD.

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (27,28).

SEARCH STRATEGY

A comprehensive literature search was performed across PubMed, Embase, MEDLINE, and the Cochrane Library for studies published up to March 2025. The search strategy included a combination of Medical Subject Headings (MeSH) and free-text keywords related to coronary artery disease (CAD) management, such as “statins,” “lipid-lowering therapy,” “percutaneous coronary intervention,” “drug-eluting stents,” “bare-metal stents,” “coronary revascularization,” and “clinical outcomes in CAD.” Boolean operators (“AND,” “OR”) were used to refine the search, and reference lists of included studies and relevant systematic reviews were also manually screened to identify additional eligible publications.

ELIGIBILITY CRITERIA

Studies were selected based on predefined inclusion and exclusion criteria. Eligible studies included randomized controlled trials (RCTs), cohort studies, case-control studies, and systematic reviews/meta-analyses that directly evaluated pharmacological strategies (e.g., statins, ezetimibe, PCSK9 inhibitors) and/or interventional approaches (e.g., PCI, stenting) in adult patients with CAD. Outcomes of interest included major adverse cardiovascular events (MACE), mortality, restenosis, revascularization rates, plaque stabilization, quality of life, and cost-effectiveness.

Exclusion criteria included studies focusing solely on pediatric or animal populations, non-English publications without translation, narrative reviews, case reports, case series, and studies not directly addressing either pharmacological therapy or stenting strategies in CAD.

STUDY SELECTION AND DATA EXTRACTION

All independent reviewers screened titles and abstracts, assessed full-text articles for eligibility, and extracted data using a standardized data collection form. Extracted variables included study design, patient demographics, intervention details (statin dosage/type, stent type, adjunctive therapy), follow-up duration, and clinical outcomes. Any disagreements between reviewers were resolved through discussion, with another reviewer consulted in cases of persistent discrepancy.

QUALITY ASSESSMENT

The risk of bias for RCTs was assessed using the Cochrane Risk of Bias tool, evaluating domains such as random sequence generation, allocation concealment, blinding, incomplete outcome data, and selective reporting (29). Non-randomized studies were assessed using the ROBINS-I tool, considering potential confounding, participant selection, classification of interventions, and outcome reporting bias (30). Systematic reviews were evaluated using the AMSTAR 2 checklist (31).

DATA SYNTHESIS

A narrative synthesis approach was used to summarize findings, organized into two major categories: pharmacological therapy (statins and adjunctive agents) and interventional therapy (PCI, bare-metal stents, drug-eluting stents, and novel stent technologies). Within each category, results were stratified by study design, patient population, and follow-up duration. Where comparable data were available, emphasis was placed on head-to-head comparisons of statin therapy versus stenting strategies, or combined therapeutic approaches.

STUDY SELECTION AND CHARACTERISTICS

FIGURE 1: PRISMA FLOWCHART

The 11 included studies were published between 2005 and 2023. Most studies were conducted in North America and Europe, with sample sizes ranging from 80 to 4,562 participants. Study designs included randomized controlled trials (n = 4), prospective cohorts (n = 5), and retrospective analyses (n = 2). The primary outcomes assessed were intraoperative hemodynamic changes and postoperative analgesic effectiveness.

TABLE 1. CHARACTERISTICS OF INCLUDED STUDIES

TABLE 2. SUMMARY OF KEY FINDINGS

FIGURE 2: SUMMARY OF KEY FINDINGS

TABLE 3. INTEGRATION OF PHARMACOLOGICAL VS INTERVENTIONAL STRATEGIES

FIGURE 3: RELATIVE EMPHASIS ACROSS DOMAINS

TABLE 4. RISK OF BIAS ASSESSMENT OF INCLUDED STUDIES

FIGURE 4: RISK OF BIAS ASSESSMENT.

Coronary artery disease (CAD) continues to impose a substantial global health burden, demanding strategies that not only relieve symptoms but also improve survival and reduce adverse cardiovascular outcomes. The findings of this systematic review highlight the complementary and sometimes contrasting contributions of pharmacological and interventional therapies in the management of CAD. The evolution from statins to stents represents not a competition but a continuum in which both modalities play synergistic roles depending on patient profile, disease severity, and clinical context.

Role of Pharmacological Therapy

The consistent benefit of statins across studies underscores their centrality in CAD management. Schömig et al. (2002) demonstrated a near 50% reduction in one-year mortality with statin therapy post-PCI, reinforcing their role in secondary prevention (33). Likewise, the JUPITER trial (Hsia et al., 2011) extended these benefits to primary prevention, with marked reductions in MACE and mortality among patients achieving very low LDL-C levels (35). The pleiotropic effects of statins—particularly plaque stabilization and inflammation reduction—provide a mechanistic basis for these observations, as supported by Walter et al. (2001), who linked statin use to attenuation of CRP-related recurrent risk (32).

More recently, PCSK9 inhibitors have emerged as potent lipid-lowering agents capable of achieving LDL-C levels previously unattainable with statins alone. Casula et al. (2019) confirmed reductions in cardiovascular events, while Bodapati et al. (2023) provided evidence of modest mortality benefit with alirocumab (40,42). However, high cost and limited accessibility remain barriers, confining their use to high-risk patients who do not achieve targets on standard therapy. Thus, while statins remain first-line therapy, adjunctive pharmacology is increasingly important in precision management of CAD.

Evolution of Interventional Approaches

On the interventional front, percutaneous coronary intervention (PCI) has undergone a remarkable transformation. The introduction of bare-metal stents (BMS) reduced acute vessel recoil but was soon limited by restenosis. Drug-eluting stents (DES) addressed this limitation, delivering antiproliferative drugs locally and significantly lowering reintervention rates, as confirmed by Bangalore et al. (2012) and Pedersen et al. (2014) (36,37). Yet, concerns about early stent thrombosis and, in some studies such as Lagerqvist et al. (2007), transiently increased mortality, tempered enthusiasm until newer-generation DES improved safety profiles (34).

Large pragmatic RCTs, such as NORSTENT (Wiseth & Bønaa, 2017), provided balanced evidence: while DES reduced restenosis and repeat revascularization, no mortality or MI benefit was observed compared to BMS over six years (39). These findings emphasize that stenting primarily addresses anatomical and symptomatic disease, whereas pharmacological therapy influences systemic drivers of atherosclerosis.

CABG, although more invasive, retains a vital role in complex multi-vessel and left main CAD, with Doenst et al. (2022) reinforcing its survival advantage in select populations (41). Contemporary practice increasingly uses heart team discussions to guide decisions between PCI and CABG, emphasizing individualized treatment.

Integrating Pharmacology and Intervention

The integration of statins, PCSK9 inhibitors, and interventional techniques reflects modern evidence-based care. As summarized in our integration framework, pharmacological therapy reduces systemic risks (mortality, MI, inflammation), whereas interventions target local disease manifestations (restenosis, ischemia). When combined, the two strategies complement each other, offering improved outcomes compared to either approach alone. For example, optimal PCI results are dependent on aggressive lipid-lowering therapy to stabilize non-stented plaques and prevent progression of atherosclerosis elsewhere in the coronary tree.

This interplay is particularly evident in high-risk groups such as NSTE-ACS, where Pedersen et al. (2014) demonstrated that DES combined with optimal pharmacological therapy significantly reduced composite outcomes (37). The growing role of precision medicine—including genetic risk profiling, advanced imaging (IVUS, OCT), and biomarker-guided therapy—will likely refine this integration further.

Risk of Bias and Limitations of Evidence

The risk of bias assessment suggests that most contemporary RCTs and meta-analyses maintain methodological rigor, with low overall bias. Earlier cohort and registry-based studies, such as Walter et al. (2001) and Schömig et al. (2002), were limited by open-label design and potential confounding (32,33). Network meta-analyses, though valuable for indirect comparisons, introduce assumptions that warrant cautious interpretation. Furthermore, cost-effectiveness remains a critical but underexplored dimension—while statins are widely accessible and cost-efficient, PCSK9 inhibitors and DES introduce significant economic considerations that vary across healthcare systems.

Clinical Implications and Future Directions

The findings collectively reinforce that there is no “either-or” in CAD management—statins and stents serve distinct yet overlapping purposes. Statins remain indispensable for systemic disease modification, while stents offer symptomatic relief and reduced restenosis. Future therapeutic paradigms will likely emphasize integrated strategies, with PCSK9 inhibitors and emerging anti-inflammatory drugs complementing advanced stent technologies and surgical revascularization.

Future research should focus on long-term outcomes of ultra-low LDL-C levels achieved with novel agents, durability of biodegradable scaffolds, and comparative cost-effectiveness analyses across global populations. Personalized medicine approaches, guided by risk stratification and patient preferences, will be critical in refining the balance between pharmacological and interventional strategies.

This systematic review highlights the complementary evolution of pharmacological and interventional therapies in CAD. Statins transformed secondary prevention and remain foundational, while PCSK9 inhibitors extend therapeutic potential in selected patients. Interventions, particularly DES, provide durable symptom relief and reduced restenosis, though without consistent survival benefit. The optimal management of CAD lies in integration rather than substitution—leveraging pharmacological risk reduction with interventional precision to maximize survival, quality of life, and cost-effectiveness.

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