P186 PROLONGED ASYSTOLIA REQUIRING CRP ON THERAPY WITH TICAGRELOR AND CYCLOSPORINE

Abstract

64–year–old man, from SriLanka, affected by arterial hypertension, complicated diabetes mellitus (retinopathy, vasculopathy, peripheral neuropathy) and chronic kidney injury in hemodialysis. Liver transplantation for hepatocarcinoma due to alcholic cirrhosis required cyclosporine as immunosuppressive agent. He also suffered from chronic multifactorial anemia and mild thrombocytopenia. Home therapy included atenolol 50mg, clonidine, lercanidipine, insulin, kayexalate, cyclosporine. He was admitted in ED for a chest pain during hemodialysis, associated with high blood pressure values and lateral ST–depression on ECG. Iv nitroglycerin relieved symtoms and normalized the repolarization. Echocardiogram showed a concentric ventricular hypertrophy, without wall motion changes or significant valvulopathy. Laboratory tests detected the known anemia, thrombocytopenia (Hb 9.6g/dl, PLT 100x109/L) and renal injury (creat 10mg/dl, K + 5.1mmol/L) with a stable rise of troponin T hs 80pg/ml (n.v.<14). Aspirin and ticagrelor 180mg were administered and Patient admitted for unstable angina. Coronary angiography (femoral approach) was performed and revealed a critical stenosis of proximal IVA with subocclusion of diagonal branch; no other significant lesion was detected. Coronary artery disease was effectively treated by PCI with 2 DES. During the 2nd day of hospitalization an asystolia up to 10” occurred and atenolol was stopped. The next day, he had a new diurnal sinus arrest, lasting about 40”; external pacing had no efficacy. After CPR, he had a ROSC with recovery of sinus rhythm. No electrolyte alteration or ischemic recurrences. Aminophylline was started and ticagrelor was suspended for possible side effect enhanced by interaction with cyclosporine; shift to clopidogrel was made. No recurrence of rhythm alteration occurred neither after aminophylline interruption at 72 hours nor after reintroduction of beta–blocker on the 8th day for sinus tachycardia. Cyclosporinemia was mildly elevated. It’s known that ticagrelor is associated with a higher incidence of bradyarrhythmias mediated by increase in adenosine concentration, but these are mainly asymptomatic and nocturnal. Cyclosporine– ticagrelor interaction, through inhibition of cytochrome P450 (CYP3A4) and P–gp, increased the concentration of ticagrelor and promoted its side effect: in our case prolonged episodes of asystolia requiring CPR, solved by drug withdrawal and aminophylline with target on adenosine receptors.