A 66-year-old male with a past medical history significant for hypertension, hyperlipidemia, ischemic stroke, coronary artery disease, and asthma was admitted for cardiac catheterization for worsening angina. He had symptoms of crescendo angina with New York Heart Association (NYHA) class IV symptoms and was referred by his primary cardiologist for coronary angiography with the intent to pursue revascularization as warranted. He had established coronary artery disease in 2012, with pharmacological myocardial perfusion imaging demonstrating inferior infarct and peri-infarct ischemia with an overall preserved systolic function for which medical treatment was pursued. In 2014, he reportedly underwent coronary angiography, which demonstrated a chronic total occlusion of the right coronary artery with grade III collaterals to the right coronary system and moderate non-obstructive disease of the left circumflex artery. In the interim, he ceased tobacco smoking and received guideline-directed medical therapy. He was doing well with optimal medical therapy, which included aspirin and clopidogrel, until three weeks prior to this presentation when he noted the onset of recurrent angina. Angina initially occurred with mild exertion, subsequently progressed to angina at rest, and he was admitted to hospital with unstable crescendo angina.\nOn admission, his vital signs were stable. His physical exam was unremarkable. A 12-lead electrocardiogram (EKG) demonstrated inferior Q waves and left ventricular hypertrophy without acute ST-T abnormalities (Figure ). Cardiac biomarkers were normal (peak creatinine phosphokinase-MB (CK MB) fraction and troponin T were 9.9 ng/mL (normal range 0.0-10.4) and less than 0.03 ng/mL (<0.03 negative), respectively. Coronary angiography revealed multi-vessel coronary artery disease with a likely culprit lesion involving the proximal left circumflex artery (Videos -). He underwent successful drug-eluting stent (DES) deployment to the proximal left circumflex artery (Video ). PCI was uneventful and guideline-directed medical therapy was continued. Despite long-term adherence to clopidogrel, platelet reaction unit (PRU) was 235. Due to a high on treatment PRU, with levels greater than 208 associated with an increased risk of stent thrombosis [-], a decision was made to transition to ticagrelor. He received a single 180 mg loading dose of ticagrelor. Four hours after receiving ticagrelor, he complained of shortness of breath, throat pain, neck discomfort, and swelling of the tongue. His vital signs remained stable, and he did not exhibit any skin eruption. He demonstrated mild swelling of the tongue and significant swelling of his throat and uvula. No wheezing was noted on exam. He received supplemental oxygen and otolaryngology (ENT) consultation was sought. He was treated with dexamethasone, as well as H1 and H2 histamine blockers. After the first dose of treatment, his symptoms improved. He was closely monitored. The following morning, ENT performed flexible fiberoptic laryngoscopy, which revealed a mild edematous pharyngeal area. Based on the clinical scenario, a provisional diagnosis of ticagrelor-induced angioedema was entertained. He did not have any history of allergy to any medications, contrast medium, or heparin. The decision was made to discontinue ticagrelor. His symptoms improved over the next few days with a tapering dose of steroids and antihistamines. The final decision was made to double the dose of clopidogrel and the patient was discharged with 150 mg of clopidogrel and 81 mg of aspirin daily. He has not had any ischemic symptoms or coronary events over a six-month period of follow-up.
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.