A 50-year-old male with past medical history of ischemic heart disease and prasugrel hypersensitivity in the form of generalized rash underwent elective PCI with one drug-eluting stent (DES) to the left anterior descending artery (LAD). He was subsequently started on dual antiplatelet therapy with aspirin 81 mg daily and ticagrelor 90 mg twice a day.\nTwo days following discharge, the patient was complaining of severe shortness of breath with minimal exertion, and occasionally at rest. He denied any fevers, chills, productive cough, orthopnea, paroxysmal nocturnal dyspnea or lower limb edema. The patient’s dyspnea was heavily investigated with basic labs, cardiac biomarkers, imaging of the chest, and repeat transthoracic echocardiogram. All results came back within normal limits. The patient’s dyspnea was deemed secondary to ticagrelor use and the drug was discontinued, with subsequent improvement of his symptoms. Given his history of prasugrel hypersensitivity and current intolerance to ticagrelor, the patient was started on clopidogrel. Three days later, he presented to the emergency department (ED) with a rash that started on his chest and spread to his arms and face (Figure ).\nThe patient was diagnosed with cutaneous hypersensitivity to clopidogrel. Given the patient’s need for dual antiplatelet therapy and previously documented prasugrel hypersensitivity as well as intolerance to ticagrelor, shifting to any of them was not an option.\nReviewing the literature, three management strategies have been described for clopidogrel hypersensitivity, including switching to another agent, implementing a desensitization protocol, and a six-day course of steroids without clopidogrel discontinuation. A shared decision was made to implement the latter approach however with a slow taper over a three-week period. The patient was started on oral prednisone 30 mg twice a day for five days, followed by a decrease of 5 mg/day every three days for 15 days. On his one-week follow-up, the patient was well-tolerating clopidogrel with complete resolution of his symptoms and no significant side effects from steroids. The patient showed no side effects related to steroids on his one-month follow-up.
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.