Background: Percutaneous coronary intervention (PCI) is a pivotal treatment for patients with stable coronary artery disease (CAD), yet its overall effectiveness remains limited. Despite technological advancements, only about 5% of patients receive PCI, comparable to the 5% who are treated with pharmacological therapies. The ongoing debate between PCI and optimal drug therapy (ODT) continues, with ethylenediaminetetraacetic acid (EDTA) emerging as a notable treatment alternative. This systematic review seeks to compare the outcomes of these interventions and offer guidance for clinical decision-making. Methods: Adhering to PRISMA 2020 guidelines, this review focused on full-text articles published in English from 2012 to 2024. To ensure the inclusion of high-quality studies, editorial pieces and review articles were excluded unless they included a DOI. A comprehensive literature search was performed across several reputable databases, including ScienceDirect, PubMed, and SagePub, to collect relevant research thoroughly. Result: The review analyzed over 800 publications from these databases. After an initial screening process, eight studies were selected for detailed examination. These selected studies underwent a rigorous review to ensure comprehensive and precise evaluation. Conclusion: While both EDTA and PCI represent advanced treatment options for CAD, their effectiveness is contested due to their complexity and high costs. The systematic review indicates that PCI may offer greater benefits for patients with chronic total occlusions (CTO), showing lower mortality and myocardial infarction (MI) rates. Future research should prioritize large-scale clinical trials to further elucidate the comparative efficacy of PCI and EDTA.