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Thromb Haemost 2021; 121(10): 1376-1386
DOI: 10.1055/a-1346-3300
Atherosclerosis and Ischaemic Disease

Pharmacodynamic Profile and Prevalence of Bleeding Episode in East Asian Patients with Acute Coronary Syndromes Treated with Prasugrel Standard-Dose versus De-escalation Strategy: A Randomized A-MATCH Trial

Young-Hoon Jeong  ‡   *
1   Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon, South Korea
2   Institute of the Health Sciences, Gyeongsang National University, Jinju, South Korea
,
Ju-Hyeon Oh‡   *
3   Division of Cardiology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
,
Hyuck-Jun Yoon
4   Division of Cardiology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Daegu, South Korea
,
Yongwhi Park
1   Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon, South Korea
2   Institute of the Health Sciences, Gyeongsang National University, Jinju, South Korea
,
Jon Suh
5   Division of Cardiology, Department of Internal Medicine, Soon Chun Hyang University Bucheon Hospital, Bucheon, South Korea
,
Se-Whan Lee
6   Department of Cardiology, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea
,
Kyounghoon Lee
7   Department of Cardiology, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea
,
Jeong-Su Kim
8   Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, South Korea
,
Woo-Jung Chun
3   Division of Cardiology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
,
Yong-Hwan Park
3   Division of Cardiology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
,
Chang-Wook Nam
4   Division of Cardiology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Daegu, South Korea
,
June-Hong Kim
8   Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, South Korea
,
Jong-Hwa Ahn
9   Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, South Korea
,
Seok-Jae Hwang
9   Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, South Korea
,
Jin-Yong Hwang
2   Institute of the Health Sciences, Gyeongsang National University, Jinju, South Korea
9   Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, South Korea
,
Udaya S. Tantry
10   Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, Maryland, United States
,
Paul A. Gurbel
10   Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, Maryland, United States
,
Eun-Seok Shin
11   Division of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
› Author Affiliations Funding This study was supported by research grants from the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT, and Future Planning (NRF-2015R1A5A2008833).
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Abstract

Compared with Caucasian patients, East Asian patients have the unique risk–benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a de-escalation strategy. Before discharge, ACS patients with age <75 years or weight ≥60 kg (n = 255) were randomly assigned to the standard-dose (10-mg group) or de-escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 reaction unit [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85 ≤ PRU ≤ 208). The 250 patients completed 1-month treatment. The percentage of patients within the therapeutic window was significantly lower in the 10-mg group (n = 85) compared with the 5-mg (n = 83) and PFT-guided groups (n = 82) (35.3 vs. 67.5 vs. 65.9%) (odds ratio [OR]: 3.80 and 3.54; 95% confidence interval [CI]: 2.01–7.21 and 1.87–6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with de-escalation strategies (35.3 vs. 24.1% vs. 23.2%) (hazard ratio [HR]: 0.58 and 0.55; 95% CI: 0.30–1.14 and 0.28–1.09, respectively). “PRU < 127” was the optimal cut-off for predicting 1-month bleeding events (area under the curve: 0.616; 95% CI: 0.543–0.689; p = 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR: 2.00; 95% CI: 1.28–3.03; p = 0.001). In conclusion, compared with the standard-dose prasugrel, the prasugrel de-escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes.

Registration URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.

Keywords

acute coronary syndrome - prasugrel - East Asians - de-escalation strategy - platelet function test

* These authors contributed equally to this work.


Supplementary Material



Publication History

Received: 24 October 2020

Accepted: 02 January 2021

Accepted Manuscript online:
05 January 2021

Article published online:
03 March 2021

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