Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Autor:	Bulluck H; Leeds Teaching Hospital, National Health Service Trust, United Kingdom (H.B.).; Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, United Kingdom (H.B.)., Chong JH; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore.; Cardiovascular & Metabolic Disorders Program (J.H.C., M.C., D.J.H.), Duke-National University of Singapore Medical School., Bryant J; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore., Annathurai A; Department of Emergency Medicine, Sengkang General Hospital, Singapore (A.A., S.H.L., B.P.T.)., Chai P; Department of Cardiology, National University Heart Centre Singapore (P.C., C.-H.L., M.Y.C.)., Chan M; Cardiovascular & Metabolic Disorders Program (J.H.C., M.C., D.J.H.), Duke-National University of Singapore Medical School., Chawla A; School of Medicine, University of Colorado, Denver (A.C.)., Chin CY; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore., Chung YC; Siemens Healthcare, Singapore (Y.-C.C.)., Gao F; National Heart Research Institute Singapore (F.G., D.J.H.), National Heart Centre Singapore.; Health Services and Systems Research (F.G., M.E.H.O.), Duke-National University of Singapore Medical School., Ho HH; Department of Cardiology, Tan Tock Seng Hospital, Singapore (H.H.H., T.W.)., Ho AFW; Department of Emergency Medicine, Singapore General Hospital (A.F.W.H., M.E.H.O., E.W.)., Hoe J; Department of Radiology, Mount Elizabeth Novena Hospital, Singapore (J.H.)., Imran SS; Department of Cardiology, Khoo Teck Puat Hospital, Singapore (S.S.I., P.L.Z.Y.)., Lee CH; Department of Cardiology, National University Heart Centre Singapore (P.C., C.-H.L., M.Y.C.)., Lim B; Department of Cardiology, Asian Heart & Vascular Centre, Singapore (B.L., B.W.L.)., Lim ST; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore., Lim SH; Department of Emergency Medicine, Sengkang General Hospital, Singapore (A.A., S.H.L., B.P.T.)., Liew BW; Department of Cardiology, Asian Heart & Vascular Centre, Singapore (B.L., B.W.L.)., Zhan Yun PL; Department of Cardiology, Khoo Teck Puat Hospital, Singapore (S.S.I., P.L.Z.Y.)., Ong MEH; Health Services and Systems Research (F.G., M.E.H.O.), Duke-National University of Singapore Medical School.; Department of Emergency Medicine, Singapore General Hospital (A.F.W.H., M.E.H.O., E.W.)., Paradies V; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore., Pung XM; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore., Tay JCK; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore., Teo L; Department of Diagnostic Imaging, National University Hospital, Singapore (L.T.)., Ting BP; Department of Emergency Medicine, Sengkang General Hospital, Singapore (A.A., S.H.L., B.P.T.)., Wong A; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore., Wong E; Department of Emergency Medicine, Singapore General Hospital (A.F.W.H., M.E.H.O., E.W.)., Watson T; Department of Cardiology, Tan Tock Seng Hospital, Singapore (H.H.H., T.W.)., Chan MY; Department of Cardiology, National University Heart Centre Singapore (P.C., C.-H.L., M.Y.C.).; Yong Loo Lin School of Medicine, National University Singapore (M.Y.C., D.J.H.)., Keong YK; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore.; Cardiovascular System Academic Clinical Program (Y.K.K.), Duke-National University of Singapore Medical School., Tan JWC; Department of Cardiology (J.H.C., J.B., C.Y.C., S.T.L., V.P., X.M.P., J.C.K.T., A.W., Y.K.K., J.W.C.T.), National Heart Centre Singapore., Hausenloy DJ; National Heart Research Institute Singapore (F.G., D.J.H.), National Heart Centre Singapore.; Cardiovascular & Metabolic Disorders Program (J.H.C., M.C., D.J.H.), Duke-National University of Singapore Medical School.; Yong Loo Lin School of Medicine, National University Singapore (M.Y.C., D.J.H.).; Hatter Cardiovascular Institute, University College London, United Kingdom (D.J.H.).
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2024 Jul 09; Vol. 150 (2), pp. 91-101. Date of Electronic Publication: 2024 May 14.
DOI:	10.1161/CIRCULATIONAHA.124.068938
Abstrakt:	Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P <0.05 was considered statistically significant. Results: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P =0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P =0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P =0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. Conclusions: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723. Competing Interests: L.T. is on the Astra Zeneca international advisory board of management of adverse events with the new antibody drug conjugate T-DXd in Asian patients with metastatic breast cancer, Roche Singapore immunotherapy in early stage NSCLC patient journey advisory board. L.T. has received a Philips speaker honorarium in kind and a Siemens Healthineers speaker honorarium. Y.K.K. has received research funding from Amgen, Astra Zeneca, Abbott Vascular, Bayer, Boston Scientific, Shockwave Medical, and Novartis (via institution); consulting fees from Abbott Vascular, Medtronic, Novartis, and Peijia Medical; and speaker fees from Shockwave Medical, Abbott Vascular, Boston Scientific, Medtronic, Alvimedica, Biotronik, Orbus Neich, Amgen, Novartis, Astra Zeneca, Microport, Terumo, and Omnicare. Y.K.K. is also cofounder and owns equity in Trisail, for which OrbusNeich is an investor. D.J.H. has received consultant fees from Faraday Pharmaceuticals Inc and Boehringer Ingelheim International GmbH, honoraria from Servier, and research funding from Astra Zeneca and Merck Sharp & Dohme Corp. C.Y.C. has received speaker fees from Novartis and consultancy fees from Boston Scientific and Philips. The other authors report no conflicts.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu