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Clinical Trial
. 2024 Jul 9;150(2):91-101.
doi: 10.1161/CIRCULATIONAHA.124.068938. Epub 2024 May 14.

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)

Heerajnarain Bulluck #  1   2 , Jun Hua Chong #  3   4 , Jennifer Bryant  3 , Annitha Annathurai  5 , Ping Chai  6 , Mervyn Chan  4 , Ashish Chawla  7 , Chee Yang Chin  3 , Yiu-Cho Chung  8 , Fei Gao  9   10 , Hee Hwa Ho  11 , Andrew Fu Wah Ho  12 , John Hoe  13 , Syed Saqib Imran  14 , Chi-Hang Lee  6 , Benji Lim  15 , Soo Teik Lim  3 , Swee Han Lim  5 , Boon Wah Liew  15 , Patrick Lim Zhan Yun  14 , Marcus Eng Hock Ong  10   12 , Valeria Paradies  3 , Xuan Ming Pung  3 , Julian Cheong Kiat Tay  3 , Lynette Teo  16 , Boon Ping Ting  5 , Aaron Wong  3 , Evelyn Wong  12 , Timothy Watson  11 , Mark Y Chan  6   17 , Yeo Khung Keong  3   18 , Jack W C Tan  3 , Derek J Hausenloy  9   4   17   19 ; PITRI Investigators
Collaborators, Affiliations
Clinical Trial

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)

Heerajnarain Bulluck et al. Circulation. .

Abstract

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.

Keywords: ST-segment–elevation myocardial infarction; cangrelor; cardiovascular magnetic resonance; microvascular obstruction; myocardial infarct size; primary percutaneous coronary intervention; ticagrelor.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
CONSORT flow diagram of the PITRI trial. CABG indicates coronary artery bypass graft surgery; CMR, cardiovascular magnetic resonance; CONSORT, Consolidated Standards of Reporting Trials; IMP, investigational medicinal product; PITRI, Platelet Inhibition to Target Reperfusion Injury; PPCI, primary percutaneous coronary intervention; and STEMI, ST-segment–elevation myocardial infarction.
Figure 2.
Figure 2.
Representative T2 maps, T2* maps, and LGE images of the acute cardiovascular magnetic resonance in 2 patients. A, Patient A with subendocardial anterior MI (red arrow) and no MVO or IMH. B, Patient B with a full-thickness lateral MI (red arrow) with MVO and IMH (red arrows). IMH indicates intramyocardial hemorrhage; LGE, late gadolinium enhancement; MI, myocardial infarction; and MVO, microvascular obstruction.
Figure 3.
Figure 3.
Effect of cangrelor on acute and 6-month myocardial infarct size compared to placebo. Acute (primary efficacy end point; A) and 6-month (secondary efficacy end point; B) myocardial infarction (MI) size by cardiovascular magnetic resonance. %LVmassindicates percentage of the left ventricle mass.
Figure 4.
Figure 4.
Forest plot for prespecified subgroup analyses. LAD indicates left anterior descending; MI, myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment–elevation myocardial infarction; and TIMI, Thrombolysis in Myocardial Infarction.
See this image and copyright information in PMC

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