Aspirin Hypersensitivity in Patients with Coronary Artery Disease: An Updated Review and Practical Recommendations

Abstract

Acetylsalicylic acid (ASA) represents a cornerstone of antiplatelet therapy for the treatment of atherosclerotic coronary artery disease (CAD). ASA is in fact indicated in case of an acute coronary syndrome or after a percutaneous coronary intervention with stent implantation. Aspirin hypersensitivity is frequently reported by patients, and this challenging situation requires a careful evaluation of the true nature of the presumed sensitivity and of its mechanisms, as well as to differentiate it from a more frequent (and more easily manageable) aspirin intolerance. Two main strategies are available to allow ASA administration for patients with CAD and suspected ASA hypersensitivity: a low-dose ASA challenge, aimed at assessing the tolerability of ASA at the antiplatelet dose of 100 mg, and desensitization, a therapeutic procedure which aims to induce tolerance to ASA. For those patients who cannot undergo ASA challenge and desensitization due to previous serious adverse reactions, or for those in whom desensitization was unsuccessful, a number of further alternative strategies are available, even if these have not been validated and approved by guidelines. The aim of this state-of-the-art review is therefore to summarize the established evidence regarding pathophysiology, clinical presentation, diagnosis, and management of aspirin hypersensitivity and to provide a practical guide for cardiologists (and clinicians) who have to face the not uncommon situation of a patient with concomitant coronary artery disease and aspirin hypersensitivity.

Keywords: aspirin hypersensitivity; coronary artery disease; desensitization; low-dose ASA challenge.

Figure 1

Arachidonic acid pathway in inflammation. The Figure shows the arachidonic acid pathway and the formation of its metabolites (leukotrienes, prostaglandins, and thromboxane) through cyclooxygenase (COX-1 and COX-2) action. Acetylsalicylic acid, blocking COXs, inhibits metabolites effects and exerts anti-inflammatory and antiplatelet function. ASA: acetylsalicylic acid; PG: prostaglandin; TxA₂: thromboxane A2.

Figure 2

ASA hypersensitivity: diagnostic and therapeutic algorithm. When ASA hypersensitivity is suspected in a patient with atherosclerotic coronary artery disease, a diagnostic workout to confirm or exclude hypersensitivity is mandatory in order to perform percutaneous coronary interventions safely. A detailed clinical history can distinguish ASA intolerance from hypersensitivity signs and symptoms, above all in the presence of comorbidities (chronic rhinosinusitis, nasal polyps, asthma, food allergy). If ASA hypersensitivity is confirmed (or still suspected) in an emergency setting, PCI should be performed by administering an alternative antiplatelet drug. If patient conditions allow for 24–48 h waiting and allergologist consultation is available, LDAC and/or desensitization should be performed. ASA: acetylsalicylic acid; CAD: coronary artery disease; LDAC: low-dose ASA challenge; PCI: percutaneous coronary interventions.