Author + information
- Received April 8, 2020
- Revision received July 17, 2020
- Accepted August 4, 2020
- Published online October 5, 2020.
- Yongwhi Park, MD, PhDa,∗,
- Jin Sin Koh, MD, PhDb,∗,
- Jae-Hwan Lee, MD, PhDc,
- Jae-Hyeong Park, MD, PhDc,
- Eun-Seok Shin, MD, PhDd,
- Ju Hyeon Oh, MD, PhDe,
- Woojung Chun, MD, PhDe,
- Sang Yeub Lee, MD, PhDf,
- Jang-Whan Bae, MD, PhDf,
- Jeong Su Kim, MD, PhDg,
- Weon Kim, MD, PhDh,
- Jung-Won Suh, MD, PhDi,
- Dong Heon Yang, MD, PhDj,
- Young-Joon Hong, MD, PhDk,
- Mark Y. Chan, MD, PhDl,
- Min Gyu Kang, MDb,
- Hyun-Woong Park, MDb,
- Seok-Jae Hwang, MD, PhDb,
- Jin-Yong Hwang, MD, PhDb,
- Jong-Hwa Ahn, MD, PhDa,
- Si Wan Choi, MD, PhDc,∗ (, )
- Young-Hoon Jeong, MD, PhDa,∗∗ (, )
- on behalf of the HEALING-AMI Investigators
- aDepartment of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, South Korea
- bDepartment of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, South Korea
- cDepartment of Cardiology, Chungnam National University Hospital, Daejeon, South Korea
- dDepartment of Cardiology, Ulsan Medical Center, Ulsan Hospital, Ulsan, South Korea
- eDivision of Cardiology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
- fDepartment of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South Korea
- gDepartment of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, South Korea
- hCardiovascular Department of Internal Medicine, Kyung Hee University Hospital, Seoul, South Korea
- iDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- jDepartment of Cardiology, Kyungpook National University Hospital, Daegu, South Korea
- kDepartment of Cardiovascular Medicine, Chonnam National University Hospital, Gwangju, South Korea
- lSingapore National University Heart Center, Singapore National University Hospital, Singapore, Singapore
- ↵∗Address for correspondence:
Prof. Si Wan Choi, Chungnam National University Hospital, 282 Munwha-ro, Jung-gu, Daejeon 35015, South Korea.
- ↵∗∗Prof. Young-Hoon Jeong, Cardiovascular Center, Gyeongsang National University Changwon Hospital, 11 Samjeongja-ro, Seongsan-gu, Changwon, Gyeongsangnam-do 51472, South Korea.
Objectives The aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans.
Background Animal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction.
Methods In this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro–B-type natriuretic peptide level at 6 months.
Results Among initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro–B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m2; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m2; p = 0.056) (difference −2.3 ml/m2; 95% confidence interval: −4.8 to 0.2 ml/m2; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m2; p < 0.001), whereas no reduction was seen with clopidogrel (from 26.2 ± 8.9 to 25.6 ± 11.0 ml/m2; p = 0.366) (difference −1.8 ml/m2; 95% confidence interval: −3.5 to −0.1 ml/m2; p = 0.040).
Conclusions Ticagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534)
↵∗ Drs. Y. Park and Koh contributed equally to this paper.
This study is supported by research grants from AstraZeneca Korea and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT, and Future Planning (NRF-2015R1A5A2008833). The HEALING-AMI study was an investigator-initiated study with a research grant from AstraZeneca Korea. However, the company had no role in protocol development, study management, data collection, or data analysis other than financial sponsorship. Dr. Jeong has received honoraria for lectures from AstraZeneca, Sanofi, Daiichi-Sankyo/Lilly, Haemonetics, Otsuka, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals; and has received research grants or support from AstraZeneca, Haemonetics, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Cardiovascular Interventions author instructions page.
- Received April 8, 2020.
- Revision received July 17, 2020.
- Accepted August 4, 2020.
- 2020 American College of Cardiology Foundation
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