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 68-year-old male developed pruritic and exanthematous eruptions over a 24-hour period. He had a history of angina for the past 6 months, and he underwent elective percutaneous coronary intervention in the left anterior descending artery and left circumflex artery on June 24, 2015. Three drug-eluting stents were inserted (2 paclitaxel eluting stents, YINYI Biomedical Materials R&D Center Co., Ltd., Liaoning, China; and 1 sirolimus eluting stent, Lepu Medical Technology Co., Ltd., Beijing, China). All 3 stents were made of 316L stainless steel. Moreover, he also had a previous history of hypertension and hypercholesterolaemia. He had no history of prior drug allergy.\nDrugs included aspirin, ticagrelor, bisoprolol, and rosuvastatin. He has taken aspirin, bisoprolol, and rosuvastatin for the last 5 months, showing a good tolerance. After taking ticagrelor for 2 days, he developed pruritic and maculopapular rash on his bilateral costal margin, which was then generalized to the trunk (predominantly affected the chest and abdomen). His extremities were not affected, with no angioedema, no fever, and no arthralgia.\nThe laboratory test result showed an elevation in the leukocyte count (11.4 ×109/L) and in the neutrophil count (8.21 ×109/L). The lymphocyte count was 1.72 ×109/L and the eosinophil count was 0.58 ×109/L. The liver function test results were as follows: alanine aminotransferase, 14 U/L; aspartate aminotransferase, 27 U/L; total protein, 61.9 g/L; albumin, 40.2 g/L; total bilirubin, 36.8 µmol/L; direct bilirubin, 5.59 µmol/L; γ-glutamyltranspetidase, 61 U/L; total bile acid, 0.9 µmol/L; and lactate dehydrogenase, 380 U/L.\nHe showed to have a hypersensitive reaction to ticagrelor, and he was treated with antihistamines. Ticagrelor was switched to clopidogrel. Soon thereafter, his rash was gradually improved.\nHowever, 10 days later, he developed severe chest pain and received emergency coronary angiogram. Subacute definite stent thrombosis was confirmed, and thrombectomy was performed. After the procedure, a platelet function test was conducted, revealing a low response to clopidogrel.\nTo achieve therapeutic platelet aggregation inhibition, ticagrelor was reused under close supervision. Within approximately 2 hours, he developed generalized maculopapular rash in the whole trunk, which was resolved with intravenous corticosteroids. Ticagrelor was discontinued to avoid further hypersensitive reaction. Our patient showed delayed-type hypersensitivity reaction from the use of ticagrelor, represented in the form of generalized maculopapular rashes. Ticagrelor desensitization might not be appropriate for this patient.\nSwitching to other kinds of P2Y12 receptor antagonist antiplatelet drug was considered. Drugs that are structurally different from ticagrelor may be a good substitute for those with ticagrelor hypersensitivity. The chemical class of ticagrelor is cyclopentyl-triazolo-pyrimidine, and the other chemical class consists of thienopyridines (clopidogrel, prasugrel, ticlopidine) []. This patient presented a low response to clopidogrel and had suffered subacute in-stent thrombosis. Currently, prasugrel has not been approved for use in China. Ticlopidine has been associated with toxic side effects, such as rash, severe neutropenia, diarrhea, and thrombocytopenic purpura. Therefore, antithrombotic therapy was significantly difficult in this patient.\nThe patient ultimately received aspirin and warfarin as an antithrombotic treatment. He was given subcutaneous injection of low molecular weight heparin for 7 days. The regulated dose of warfarin was maintained in between 2 and 3 of the international normalized ratio (INR). During the follow-up period, our patient did not report any discomfort.