Acetylsalicylic Acid and Cardioprotection: Antioxidant Mechanisms, Clinical Efficacy, and Emerging Therapeutic Perspectives

Abstract

Introduction: Ischemic cardiovascular disease remains the leading cause of global morbidity and mortality. Acetylsalicylic acid (ASA) has played a key role in secondary prevention, although its use in primary prevention remains debated due to the increased risk of major bleeding. Objectives: To critically review recent evidence on ASA in cardioprotection, focusing on antioxidant mechanisms, clinical efficacy, resistance, therapeutic alternatives, and emerging perspectives. Methodology: A systematic literature review was conducted using Scopus and Web of Science (2015–2025), selecting 17 relevant original and review articles published in English. Results: Beyond its antiplatelet effect, ASA reduces oxidative stress in ischemia-reperfusion models, improving antioxidant markers. In secondary prevention, it reduces atherothrombotic events (RR 0.79) and mortality (RR 0.87). In primary prevention, its benefit is limited (HR 0.89) and associated with a higher bleeding risk (HR 1.43). The Zn(ASA)₂ complex shows greater anti-inflammatory efficacy and lower gastrointestinal toxicity in animal studies. Monotherapy with P2Y₁₂ inhibitors may offer a safer alternative. Discussion: ASA remains essential in secondary prevention, though its role in primary prevention should be individualized. Factors such as drug resistance and treatment interruption reduce its effectiveness. New formulations like Zn(ASA)₂ and alternatives such as clopidogrel show promising outcomes. Conclusion: ASA retains clinical relevance, but its future use will depend on more precise patient selection, the identification of response biomarkers, and advances in emerging therapies with improved safety profiles.