A 69-year-old African gentleman with a medical history of coronary artery disease after percutaneous coronary intervention to his right coronary artery in 2014 for a non-ST-segment elevation myocardial infarction and prior contrast-media allergy presented to the emergency department with atypical angina.\nShortly after his arrival, he was seen by the emergency medicine physician who initiated an acute coronary syndrome antiplatelet regimen comprising both oral aspirin 325 mg and ticagrelor 180 mg. Vital signs revealed mild hypertension with a blood pressure of 147/94 mmHg, normal pulse rate of 74 beats per minute, and an oxygen saturation of 99% on pulse oximetry on room air. His physical examination was significant for left-sided chest wall tenderness only. A 12-lead electrocardiogram (EKG) revealed sinus rhythm with a 1st degree atrioventricular block and a left anterior fascicular block with prior inferior myocardial infarction. There were no acute ischemic changes. His cardiac biomarkers were normal (peak serum levels of creatine phosphokinase-MB fraction (CK-MB) and troponin T were 1.5 ng mL−1 (normal range, 1–5 ng mL−1) and 0.034 ng mL−1 (normal range, 0-0.1 ng mL−1), respectively) and did not reflect a myocardial infarction.\nApproximately 1 hour after ticagrelor administration, the patient reported a constellation of symptoms which included worsening chest pain, sudden-onset respiratory distress, and generalized urticaria. His repeat physical examination revealed new-onset periorbital edema and angioedema (). He was immediately administered 200 mg intravenous hydrocortisone, 100 mg intravenous ranitidine, and 10 mg intravenous chlorphenamine with nebulized albuterol and ipratropium, and his symptoms resolved shortly thereafter (within an hour).\nBased on the clinical scenario, the patient's tentative diagnosis was ticagrelor-induced hypersensitivity reaction with angioedema as this was the only new medication he was given (he was on daily maintenance aspirin for his CAD and previously tolerated a 1-year course of clopidogrel after drug-eluting stent implantation). It was also noted that he was not on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. He was subsequently transferred to cardiac care unit for further observation and supportive care. The following day, a 2D transthoracic echocardiogram revealed a preserved left ventricular ejection fraction of 60% without regional wall motion abnormalities. He reported that his symptoms were much improved and was hemodynamically stable. His clinical angioedema completely resolved. The patient's atypical angina completely abated, and subsequent cardiac biomarkers and electrocardiograms were unremarkable. As a result, inpatient coronary angiography was not pursued as his TIMI risk stratification was considered low to moderate risk, and outpatient exercise stress echocardiography was the preferred management strategy to assess for ischemia. He was safely discharged on guideline-recommended, optimal medical therapy comprising aspirin, clopidogrel (which he previously tolerated as DAPT for his prior stent implantation without any adverse effects), beta-blocker, mineralocorticoid receptor antagonist with high-intensity statin, and a tapered course of oral steroid therapy.
A 57-year-old man with significant history of ischaemic heart disease underwent elective percutaneous coronary intervention to the proximal left anterior descending artery with insertion of two drug-eluting stents in February 2014. He was commenced on dual antiplatelet therapy with the addition of clopidogrel to his regular aspirin. His other past medical history included hypertension and hypercholesterolaemia. He had no previous history of drug allergy or atopy.\nEleven days after commencement of clopidogrel he developed a generalised urticarial rash including his scalp and palms, with associated peripheral paraesthesia. He was treated with antihistamines and his clopidogrel was changed to ticagrelor.\nThirty-six hours after the introduction of ticagrelor, he represented with facial angioedema associated with left sided chest pain and dysphagia without respiratory compromise. Following the cessation of ticagrelor, the symptoms resolved with intramuscular adrenaline and intravenous corticosteroids and he was discharged home after a period of observation.\nFurther cardiology consultation recommended the trial of prasugrel under close supervision. Within two hours, he developed an urticarial reaction involving the hands, feet and groin, which initially resolved with antihistamine. After the third dose of prasugrel, he experienced chest, left arm and abdominal discomfort, with periorbital and lip angioedema. Although haemodynamically stable, he was diaphoretic and required oxygen therapy. Again, he improved with intramuscular adrenaline, intravenous f luid and oral and intravenous antihistamines. All investigations were unremarkable including the tryptase level which was only collected 36 hours post symptom onset.\nThe idea of trialling a fourth antiplatelet agent, ticlopidine, was briefly considered. Given his reaction to three antiplatelet agents, and after reviewing the molecular structure of all four drugs (), as well as available literature on clopidogrel sensitisation and its cross-reactivity towards ticlopidine and prasugrel, there was significant concern about the risk of similar but more severe and rapid onset hypersensitivity reaction. The patient ultimately underwent clopidogrel desensitisation with prednisolone cover. He successfully completed the programme without complication and was maintained on strict daily dose afterwards. He continues to take clopidogrel without adverse effects four months post desensitisation.