20.500.12556/RUL-165128 Inhibicija trombocitov s kangrelorjem pri komatoznih bolnikih po izvenbolnišničnem srčnem zastoju in primarni perkutani koronarni intervenciji Platelet inhibition with cangrelor in comatose survivors of out-of-hospital cardiac arrest undergoing primary percutaneous coronary intervention Utemeljitev in namen. Komatozni bolniki po izvenbolnišničnem srčnem zastoju (OHCA) in urgentni perkutani koronarni intervenciji (PCI), ki jih zdravimo s terapevtsko hipotermijo (TTM), imajo visoko tveganje za trombozo v stentu. Delno je vzrok zapoznela zavora trombocitov kljub uporabi potentnih zaviralcev receptorjev P2Y12. Želeli smo preučiti ali infuzija parenteralnega zaviralca P2Y12 kangrelorja, takoj in ustrezno zavre trombocite do učinkovanja tikagrelorja, apliciranega po enteralni sondi in s tem premosti obdobje nezadostne inhibicije trombocitov. Metode. Med julijem 2019 in novembrom 2021 smo randomizirali 30 zaporednih bolnikov po OHCA in PCI, zdravljenih s TTM, v preiskovano skupino bolnikov s kangrelorjem in kontrolno skupino. Vsi bolniki so prejeli acetilsalicilno kislino in nefrakcionirani heparin ter po enteralni sondi apliciran tikagrelor. Preiskovana skupina je ob začetku PCI prejela še intravenski polnilni odmerek in štiriurno infuzijo kangrelorja. Reaktivnost trombocitov smo izmerili z metodama VerifyNow® and Multiplate® ADP ob začetku PCI ter 1, 3, 5 in 8 ur po začetku PCI. Rezultati. Med skupinama nismo ugotavljali razlik v karakteristikah bolnikov. Reaktivnost trombocitov z VerifyNow® je bila znižana v skupini bolnikov, ki so prejeli kangrelor po eni (30 proti 221 PRU; p < 0,001) in treh urah (24 proti 180 PRU; p < 0,001), razlik po petih in osmih urah nismo ugotavljali. Delež bolnikov z visoko reaktivnostjo trombocitov je bil nižji pri preiskovani skupini; 0 % proti 67 % po eni (p < 0,001) ter 0 % proti 47 % po treh urah (p = 0,007). Meritve z Multiplate® ADP so bile skladne z VerifyNow®, z razliko po eni (14 proti 48 AU, p < 0,001) in treh urah (11 proti 42 AU, p = 0,001). Pogostejših krvavitev v preiskovani skupini nismo beležili. Sklepi. Infuzija kangrelorja pri preiskovanem vzorcu bolnikov inducira takojšnjo in zadostno zavoro trombocitov v času neučinkovite inhibicije do ustreznega delovanja tikagrelorja. Interakcije med obema zdraviloma nismo ugotavljali. Background and aim. Comatose survivors of out-of-hospital cardiac arrest (OHCA) undergoing percutaneous coronary intervention (PCI) and target temperature management are at increased risk of stent thrombosis (ST) which may be partially explained by delayed onset of platelet inhibition even after novel P2Y12 agents. We hypothesized that periprocedural intravenous cangrelor will induce immediate and profound platelet inhibition and thereby bridge the “P2Y12 inhibition gap”. Methods. Between July 2019 and November 2021, 30 consecutive comatose patients after OHCA undergoing PCI and mild therapeutic hypothermia were randomized to cangrelor and control groups. All patients received standard doses of unfractioned heparin, acetylsalicylic acid and crushed/dissolved tablets of ticagrelor via enteral tube. The cangrelor group received an intravenous bolus of cangrelor followed by 4-hour infusion. Platelet aggregation was measured by VerifyNow® and Multiplate® ADP at baseline and 1, 3, 5 and 8 hours after passage of PCI guidewire. Results. There was no significant difference in patient characteristics. Platelet reactivity according to VerifyNow® was decreased in cangrelor group at one (30 vs 221 PRU; p < 0,001) and three hours (24 vs 180 PRU; p < 0,001) with no change at five and eight hours. This effect was mirrored in decreased high on-treatment platelet reactivity (HPR) in cangrelor group at one (0 % vs 67%; p < 0,001) and three hours (0 % vs 47 %; p = 0,007). Multiplate® ADP was also significantly decreased at one (14 vs 48 U; p < 0,001) and three hours (11 vs 42 U; p = 0,001). No difference in bleeding rates was observed. Conclusions. In comatose survivors of OHCA undergoing PCI and mild therapeutic hypothermia, cangrelor safely induced immediate and profound platelet inhibition thereby bridging the “P2Y12 inhibition gap” after ticagrelor. There was no rebound in platelet reactivity after discontinuation of cangrelor infusion indicating lack of drug-drug interaction. Primarni izvenbolnišnični srčni zastoj Inhibicija trombocitov Kangrelor Primarna perkutana koronarna intervencija Terapevtska hipotermija Primary out-of-hospital cardiac arrest Platelet inhibition Cangrelor Primary percutaneous coronary intervention Therapeutic hypothermia true false false Slovenski jezik Angleški jezik Doktorsko delo/naloga 2024-11-23 08:15:31 2024-11-23 08:15:36 2024-11-24 04:08:52 0000-00-00 00:00:00 2024 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 30253 6528.pdf 6528.pdf 1 96EFC291AEFF05AD0B8D319938EAD535 ec23d75a9a5b8a9bdfe394d0e69f10ddaf15a0312ddc96241005e46bb2acb4d1 55569854-a96a-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=196103 Medicinska fakulteta 0 0 0