Background: Aspirin plays a central role in the treatment of acute coronary syndromes (ACS), significantly reducing thrombotic complications. However, aspirin hypersensitivity, although uncommon, presents a serious therapeutic challenge. Rapid desensitisation is recommended in selected cases, but allergic reactions may still limit its success.
Objective: To review current evidence on the management of aspirin hypersensitivity in ACS and illustrate the clinical decision-making process through a representative case involving failed desensitisation and alternative therapeutic planning.
Methods: A literature review was conducted using PubMed and Scopus (2000–2025), focusing on the prevalence, pathophysiology, and management strategies for aspirin hypersensitivity in ACS. A case of aspirin hypersensitivity in high-risk non-ST elevation ACS is presented to contextualise the clinical challenges.
Case report: A 78-year-old man was admitted to the cardiology ward with high-risk non-ST elevation ACS, evidenced by myocardial injury biomarkers and regional wall motion abnormalities in the left anterior descending artery territory. Due to a prior history of cutaneous allergic reactions to aspirin, the patient was initially treated with clopidogrel monotherapy. A desensitisation protocol was initiated prior to planned coronary angiography. However, during the first step (10 mg aspirin), the patient developed angioedema of the lower lip, prompting immediate termination of the protocol. As a result, only diagnostic coronary angiography was performed, revealing severe left main and triple-vessel disease. Given the extent and complexity of coronary artery disease, the case was reviewed in a multidisciplinary heart team meeting. Surgical revascularisation was selected as the optimal therapeutic strategy, and the patient was referred for coronary artery bypass grafting (CABG), staying with clopidogrel in monotherapy.
Discussion: Aspirin desensitisation is often feasible and safe, but not always successful. In cases where hypersensitivity persists, careful risk–benefit assessment is essential. In selected patients, surgical revascularisation may offer a safer and more definitive option when DAPT cannot be achieved pharmacologically.
Conclusion: Aspirin hypersensitivity in ACS remains a complex clinical dilemma. This case highlights the importance of multidisciplinary decision-making in optimising outcomes for high-risk patients with limited pharmacologic options.