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, Jun Hua Chong, Jennifer Bryant, Annitha Annathurai, Ping Chai, Mervyn H.H. Chan, Ashish Chawla, Chee Yang Chin, Yiu‐Cho Chung, Fei Gao, Hee Hwa Ho, Andrew Fu Wah Ho, John Hoe, Syed Saqib Imran, Chi‐Hang Lee, Benji Lim, Soo Teik Lim, Swee Han Lim, Boon Wah Liew, Patrick Zhan‐Yun Lim, Marcus Eng Hock Ong, Valeria Paradies, Xuan Ming Pung, Julian Cheong Kiat Tay, Lynette Teo, Boon Ping Ting, Aaron Wong, Evelyn Wong, Timothy Watson, Mark Y. Chan, Yeo Khung Keong, Jack Wei Chieh Tan, Derek J. Hausenloy, Jack W. Tan, Derek J. Hausenloy, C. Chi, Julian Tay, Pung Xuan Ming, Kamalesh Anbalakan, Keh Yann San, Kenneth Keen Yip Chew, Michelle MY Chan, Hong Rilong, Kui Swee Leng, Lim Soo Teik, Audry Lee, Felix Maverick Rubillar, James J. Cai, Jonathan Yap, W. Yan, Ho Kay Woon, Lim Fang Yi, Shen Xia Yen, Ruan Xucong, Yeo Khung Keong, Jun Hua Chong, Jennifer Bryant, Terrance Chua, Chee Yang Chin, Valeria Paradies, Aaron Wong, Leong Bahru, Tina Teo, Tan Ru San, Tang Hak Chiaw, Calvin Chin, F Ang, Min-Tun Kyaw, S. Priyalatha, Jia-Mei Chua, Deborah Yip, Rosalind Lee, Katherina Oh, Ho Pei Yi, Leow Wanshan, Syamimi Atiqa Binte Rahmat, Gan Yar Chze, Derek J. Hausenloy, Fei Gao, Shi Yan Tan, Mervyn H.H. Chan, Lateef Fatimah, Andrew Fu Wah Ho, Wee Choon Peng Jeffrey, Swee Han Lim, Marcus Ong Eng Hock, Evelyn Wong, Kenneth Tan Boon Kiat, Venkataraman Anantharaman, Mark Y. Chan, Chi‐Hang Lee, Chai Ping, Low Adrian, CHAN Kok Hui, Loh Poay Huan, Wang Yi-Ting Laureen, Chen Zhengfeng Jason, Mayank Dalakoti, Perryn Ng, Sia Ching Hui
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.