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)
Authors: Bulluck Heerajnarain , Chong Jun Hua , Bryant Jennifer , Annathurai Annitha , Chai Ping , Chan Mervyn , Chawla Ashish , Chin Chee Yang , Chung Yiu-Cho , Gao Fei , Ho Hee Hwa , Ho Andrew Fu Wah , Hoe John , Imran Syed Saqib , Lee Chi-Hang , Lim Benji , Lim Soo Teik , Lim Swee Han , Liew Boon Wah , Zhan Yun Patrick Lim , Ong Marcus Eng Hock , Paradies Valeria , Pung Xuan Ming , Tay Julian Cheong Kiat , Teo Lynette , Ting Boon Ping , Wong Aaron , Wong Evelyn , Watson Timothy , Chan Mark Y. , Keong Yeo Khung , Tan Jack W.C. , Hausenloy Derek J. , Tan Jack W.C. , Hausenloy Derek J. , Chi Chee-Tang , Tay Julian , Xuan Ming Pung , Anbalakan Kamalesh , Yann San Keh , Chew Kenneth , Chan Michelle , Rilong Hong , Swee Leng Kui , Soo Teik Lim , Lee Audry , Maverick Rubillar Felix , Cai James , Yap Jonathan , Ning Yan Wong , Kay Woon Ho , Fang Yi Lim , Xia Yen Shen , Xucong Ruan , Khung Keong Yeo , Hua Chong Jun , Bryant Jennifer , Chua Terrance , Yang Chin Chee , Paradies Valeria , Wong Aaron , Bahru Leong , Teo Tina , Ru San Tan , Hak Chiaw Tang , Chin Calvin , Ang Florence , Kyaw Min-Tun , Priyalatha S. , Chua Jia-Mei , Yip Deborah , Lee Rosalind , Oh Katherina , Pei Yi Ho , Wanshan Leow , Atiqa Binte Rahmat Syamimi , Yar Chze Gan , Hausenloy Derek J. , Gao Fei , Yan Tan Shi , Chan Mervyn , Fatimah Lateef , Ho Andrew , Choon Peng Jeffrey Wee , Han Lim Swee , Ong Eng Hock Marcus , Wong Evelyn , Tan Boon Kiat Kenneth , Venkataraman Anantharaman , Chan Mark Y. , Lee Chi-Hang , Ping Chai , Fatt Hoe Adrian Low , Koo Hui Chan , Poay Huan Loh , Yi-Ting Laureen Wang , Zhengfeng Jason Chen , Dalakoti Mayank , Ng Perryn , Ching Hui Sia , Chook Shaun , Yip Alfred , Zhe Yan Ng , Hartanto Djohan Andie , Houdmont Marie , Chew Nicholas , Jiamin Siew , Ng Faclin , Teo Lynette , Ching Ong Ching , Song Junda , Kuang Low Choong , Shalini Nair , Francis Prabath Joseph , Ho Hee-Hwa , Mahadi Tasha , Watson Timothy , Ong Paul , Xin Ni Koo , Chai Jun Hui Tony , Yue Ting Ho , Zhi Lin Deanna Khoo , Lee Jin Hyun Deborah , Ki Fung Cliff Li , Low Jun Bang Randal , Joo Hor Tan , Ke Xuan Jessica Ng , Jia Min Chua , Wei Sheng Jonathan Ong , Xuyan Teoh , Shu Qi Benita Chiang , Sim Wen Jun Eran , An Shing Ang , Jia-ling Stephanie Quek , Rui Yi Pang , Ahmad Hatib Muhammad Alimi Bin , Jin Hyun Lee , Shiane Lim , Chong Keat Tan , Shonda Ng , Hoe John , Tan Jack , Chee Yang Chin , Jian Ming Fam , Raudha Siti , Annathurai Annitha , Ping Ting Boon , Chawla Ashish , Saqib Imran Syed , Lim Zhan Yun Patrick , Tan Alvin , Lim Benji , Wah Liew Boon , Thon Hon Yong 
Published: May 2024

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.