Ticagrelor Versus Clopidogrel in Comatose Survivors of Out-of-Hospital Cardiac Arrest Undergoing Percutaneous Coronary Intervention and Hypothermia

Comatose survivors of out-of-hospital cardiac arrest increasingly undergo immediate percutaneous coronary intervention (PCI) and stenting, which is associated with the need for administration of P2Y12 inhibitor.1 Because these patients remain intubated and mechanically ventilated after reestablishment of spontaneous circulation, administration of crushed and dissolved tablets by nasogastric tube remains the only option.Because the antiplatelet effect of clopidogrel is significantly decreased during the first 48 hours after reestablishment of spontaneous circulation, 2 we hypothesized that a novel P2Y12 inhibitor, ticagrelor, which does not require metabolic activation in the liver, might result in faster and stronger platelet inhibition.Consecutive comatose survivors of out-of-hospital cardiac arrest with reestablishment of spontaneous circulation undergoing immediate PCI receiving a periprocedural bolus of 250 to 500 mg acetylsalicylic acid (Aspegic, Sanofi-Aventis) and unfractionated heparin to target activated clotting time between 250 and 300 seconds were randomized to ticagrelor (Brilique, AstraZeneca) or clopidogrel (Plavix, Bristol-Myers Squibb) with a random table and sealed envelope system.The tablets were crushed, dissolved into 15 to 20 mL of distilled water, and injected using a nasogastric tube.Ticagrelor was administered as 180 mg loading and then 90 mg every 12 hours.Clopidogrel was given as 600 mg loading and then 75 mg per day together with a 100-mg daily dose of acetylsalicylic acid.Patients were cooled to 32 o C to 34 o C for 24 hours and then were subject to spontaneous rewarming.Before PCI and 2, 4, 12, 22, and 48 hours after P2Y12 loading, platelet function was measured by VerifyNow P2Y12 Test (Accriva Diagnostics,) and Multiplate (Roche, Switzerland).For VerifyNow, platelet reactivity was expressed in P2Y12 reaction units (PRUs), and in % inhibition, it was calculated as [(1-(P2Y12 receptor blockade/Basal platelet reactivity) x 100].For Multiplate, arbitrary aggregation units were used.High on-treatment platelet reactivity was defined as >208 PRU, <11% inhibition, and >46 U. 3 In-hospital incidence of definite stent thrombosis, bleeding defined as BARC 3a and 5, 4 and survival with good neurological outcome were documented.Differences between the groups were analyzed using the χ2 test or Fischer exact test for categorical variables, and Student t test or Mann-Whitney U test was used for numeric variables.Linear mixed modeling was used to assess the significance at the various time points.P<0.05 was considered significant.The study (Clinical Trial Registration: URL: https://clinicaltrials. gov.Unique identifier: NCT02224274) was approved by the Slovenian National Ethic Committee (Number 112/04/14), which waived the need for informed consent.Among 70 consecutive patients admitted between April 2014, and June 2016, 37 were randomized to either ticagrelor (20) or clopidogrel (17).Reasons for exclusion were intraprocedural eptifibatide/thrombolysis (11), decision of attending physician (8), significant bleeding (7), P2Y12 inhibitors/warfarin pretreatment (6), and bradycardia (1).One patient randomized to clopidogrel was excluded because of essential thrombocytosis.Ticagrelor and clopidogrel groups were well balanced in terms of age,