Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Patients With Stable Coronary Artery Disease Results of the SWAP-2 Study (Switching Anti Platelet-2)

被引：71

作者：

Angiolillo, Dominick J. ^{[1
]}

Curzen, Nicholas ^{[2
]}

Gurbel, Paul ^{[3
]}

Vaitkus, Paul ^{[4
]}

Lipkin, Fred ^{[4
]}

Li, Wei ^{[4
]}

Jakubowski, Joseph A. ^{[5
]}

Zettler, Marjorie ^{[5
]}

Effron, Mark B. ^{[5
]}

Trenk, Dietmar ^{[6
]}

机构：

[1] Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL 32209 USA

[2] Southampton Univ Hosp, Southampton, Hants, England

[3] Sinai Hosp, Sinai Ctr Thrombosis Res, Baltimore, MD 21215 USA

[4] Daiichi Sankyo Inc, Med Affairs, Parsippany, NJ USA

[5] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

[6] Univ Herzzentrum Freiburg Bad Krozingen, Clin Cardiol & Angiol 2, Dept Clin Pharmacol, Bad Krozingen, Germany

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2014年 / 63卷 / 15期

基金：

美国国家卫生研究院;

关键词：

drug interaction; pharmacodynamics; platelet function; prasugrel; ticagrelor; CLOPIDOGREL; REACTIVITY; INTERVENTION; INHIBITION; NONRESPONDERS; VARIABILITY; GUIDELINES; MANAGEMENT; EVENTS; UPDATE;

D O I：

10.1016/j.jacc.2013.11.032

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives The goal of this study was to evaluate the pharmacodynamic effects of switching patients from ticagrelor to prasugrel. Background Clinicians may need to switch between more potent P2Y(12) inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues. Methods After a 3-to 5-day run-in phase with a ticagrelor 180-mg loading dose (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin-treated patients (N = 110) with stable coronary artery disease were randomized to continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a 60-mg LD. Pharmacodynamic assessments were defined according to P2Y(12) reaction unit (PRU) (P2Y(12) assay) and platelet reactivity index (vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 h and 7 days after randomization. Results Platelet reactivity was significantly greater at 24 and 48 h after switching to prasugrel versus continued therapy with ticagrelor, although to a lesser extent in those receiving an LD. Mean PRU remained significantly higher in the combined prasugrel groups versus the ticagrelor group (least-squares mean difference: 46 [95% confidence interval 25 to 67]) and did not meet the primary noninferiority endpoint (upper limit of the confidence interval <= 45), although PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of high on-treatment platelet reactivity were higher at 24 and 48 h in both prasugrel groups. At 7 days, there was no difference in high on-treatment platelet reactivity rate between the combined prasugrel and ticagrelor groups. Conclusions Compared with continued ticagrelor therapy, switching from ticagrelor to prasugrel therapy was associated with an increase in platelet reactivity that was partially mitigated by the administration of an LD. (C) 2014 by the American College of Cardiology Foundation

引用

页码：1500 / 1509

页数：10

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