Yongwhi Park1, Jin Sin Koh2, Jae-Hwan Lee3, Jae-Hyeong Park3, Eun-Seok Shin4, Ju Hyeon Oh5, Woojung Chun5, Sang Yeub Lee6, Jang-Whan Bae6, Jeong Su Kim7, Weon Kim8, Jung-Won Suh9, Dong Heon Yang10, Young-Joon Hong11, Mark Y Chan12, Min Gyu Kang2, Hyun-Woong Park2, Seok-Jae Hwang2, Jin-Yong Hwang2, Jong-Hwa Ahn1, Si Wan Choi13, Young-Hoon Jeong14. 1. Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, South Korea. 2. Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, South Korea. 3. Department of Cardiology, Chungnam National University Hospital, Daejeon, South Korea. 4. Department of Cardiology, Ulsan Medical Center, Ulsan Hospital, Ulsan, South Korea. 5. Division of Cardiology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea. 6. Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South Korea. 7. Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, South Korea. 8. Cardiovascular Department of Internal Medicine, Kyung Hee University Hospital, Seoul, South Korea. 9. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. 10. Department of Cardiology, Kyungpook National University Hospital, Daegu, South Korea. 11. Department of Cardiovascular Medicine, Chonnam National University Hospital, Gwangju, South Korea. 12. Singapore National University Heart Center, Singapore National University Hospital, Singapore, Singapore. 13. Department of Cardiology, Chungnam National University Hospital, Daejeon, South Korea. Electronic address: siwanc@cnu.ac.kr. 14. Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, South Korea. Electronic address: goodoctor@naver.com.
Abstract
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).
RCT Entities:
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).
Authors: Leonid N Maslov; Sergey V Popov; Alexandr V Mukhomedzyanov; Ivan A Derkachev; Vyacheslav V Ryabov; Alla A Boshchenko; N Rajendra Prasad; Galina Z Sufianova; Maria S Khlestkina; Ilgiz Gareev Journal: Korean Circ J Date: 2022-10 Impact factor: 3.101