Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study

被引:199
作者
Valgimigli, Marco [1 ,2 ]
Campo, Gianluca [1 ]
de Cesare, Nicoletta [3 ]
Meliga, Emanuele [4 ]
Vranckx, Pascal [5 ]
Furgieri, Alessandro [6 ]
Angiolillo, Dominick J. [7 ]
Sabate, Manel [8 ]
Hamon, Martial [9 ]
Repetto, Alessandra [10 ]
Colangelo, Salvatore [11 ]
Brugaletta, Salvatore [8 ]
Parrinello, Giovanni [12 ]
Percoco, Gianfranco [13 ]
Ferrari, Roberto [1 ,2 ]
机构
[1] Univ Ferrara, Dept Cardiol, I-44100 Ferrara, Italy
[2] IRCCS, Salvatore Maugeri Fdn, Cardiovasc Res Ctr, Gussago, BS, Italy
[3] Policlin S Marco, Zingonia, BG, Italy
[4] San Giovanni Bosco Hosp, Cardiovasc Intervent Lab, Turin, Italy
[5] Virga Jesseziekenhuis, Hasselt, Belgium
[6] Cecilia Hosp, Dept Med & Surg Cardiol, Cotignola, RA, Italy
[7] Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA
[8] St Paul Univ Hosp, Dept Cardiol, Intervent Cardiol Unit, Barcelona, Spain
[9] Univ Hosp Caen, Dept Cardiol, Normandy, France
[10] Policlin San Matteo, Fdn IRCCS, Ist Ricovero & Cura Carattere Sci, I-27100 Pavia, Italy
[11] Azienda Osped S Giovanni Battista, Unit Cardiol, Turin, Italy
[12] Univ Brescia, Med Stat Unit, Brescia, Italy
[13] Lagosanto Hosp, Lagosanto, Italy
关键词
angioplasty; aspirin; clinical trials; clopidogrel; glycoproteins; OF-CARE ASSAY; MYOCARDIAL-INFARCTION; CLINICAL-TRIAL; REACTIVITY; VARIABILITY; ABCIXIMAB; EVENTS; IMPACT; RISK; RESPONSIVENESS;
D O I
10.1161/CIRCULATIONAHA.108.833236
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Inhibition of platelet aggregation after aspirin or clopidogrel intake varies greatly among patients, and previous studies have suggested that poor response to oral antiplatelet agents may increase the risk of thrombotic events, especially after coronary angioplasty. Whether this reflects suboptimal platelet inhibition per se, which might benefit from more potent antiplatelet agents such as tirofiban, is unknown. Methods and Results-We screened 1277 patients to enroll 93 aspirin, 147 clopidogrel, and 23 dual poor responders, based on a point-of-care assay, who underwent elective coronary angioplasty at 10 European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double-blind manner to receive either tirofiban (n=132) or placebo (n=131) on top of standard aspirin and clopidogrel therapy. The primary end point, consisting of troponin I/T elevation at least 3 times the upper limit of normal, was attained in 20.4% (n=27) in the tirofiban group compared with 35.1% (n=46) in the placebo group (relative risk, 0.58; 95% confidence interval, 0.39 to 0.88; P=0.009). The rate of major adverse cardiovascular events within 30 days in the tirofiban group also was reduced (3.8% versus 10.7%; P=0.031). The overall incidence of bleeding was low, likely explained by a substantial use of the transradial approach, and did not differ between the 2 groups. Conclusions-In low-risk patients according to clinical presentation who had poor responsiveness to standard oral platelet inhibitors via a point-of-care assay, intensified platelet inhibition with tirofiban lowers the incidence of myocardial infarction after elective coronary intervention. (Circulation. 2009; 119: 3215-3222.)
引用
收藏
页码:3215 / 3222
页数:8
相关论文
共 37 条
[21]   Clopidogrel loading with eptifibatide to arrest the reactivity of platelets - Results of the clopidogrel loading with eptifibatide to arrest the reactivity of platelets (CLEAR PLATELETS) study [J].
Gurbel, PA ;
Bliden, KP ;
Zaman, KA ;
Yoho, JA ;
Hayes, KM ;
Tantry, US .
CIRCULATION, 2005, 111 (09) :1153-1159
[22]   Platelet function monitoring in patients with coronary artery disease [J].
Gurbel, Paul A. ;
Becker, Richard C. ;
Mann, Kenneth G. ;
Steinhubl, Steven R. ;
Michelson, Alan D. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 50 (19) :1822-1834
[23]   Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement [J].
Hochholzer, Willibald ;
Trenk, Dietmar ;
Bestehorn, Hans-Peter ;
Fischer, Benjamin ;
Valina, Christian M. ;
Ferenc, Miroslaw ;
Gick, Michael ;
Caputo, Angelika ;
Buettner, Heinz Joachim ;
Neumann, Franz-Josef .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2006, 48 (09) :1742-1750
[24]   A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel [J].
Kastrati, A ;
Mehilli, J ;
Schühlen, H ;
Dirschinger, J ;
Dotzer, F ;
ten Berg, JM ;
Neumann, F ;
Bollwein, H ;
Volmer, C ;
Gawaz, M ;
Berger, PB ;
Schomig, A .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (03) :232-238
[25]   Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention - The role of dual drug resistance [J].
Lev, EI ;
Patel, RT ;
Maresh, KJ ;
Guthikonda, S ;
Granada, J ;
DeLao, T ;
Bray, PF ;
Kleiman, NS .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2006, 47 (01) :27-33
[26]   The 2007 revised ESC/ESH Guidelines in the management of hypertension: clarifying individual patient care [J].
MacFadyen, R. J. .
JOURNAL OF HUMAN HYPERTENSION, 2007, 21 (10) :757-761
[27]  
Marcucci Rossella, 2007, Atherosclerosis, V195, pe217, DOI 10.1016/j.atherosclerosis.2007.04.048
[28]   Variable platelet response to aspirin and clopidogrel in atherothrombotic disease [J].
Maree, Andrew O. ;
Fitzgerald, Desmond J. .
CIRCULATION, 2007, 115 (16) :2196-2207
[29]   Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction [J].
Matetzky, S ;
Shenkman, B ;
Guetta, V ;
Schechter, M ;
Bienart, R ;
Goldenberg, I ;
Novikov, I ;
Pres, H ;
Savion, N ;
Varon, D ;
Hod, H .
CIRCULATION, 2004, 109 (25) :3171-3175
[30]   Randomized clinical trial of abciximab in diabetic patients undergoing elective percutaneous coronary interventions after treatment with a high loading dose of clopidogrel [J].
Mehilli, J ;
Kastrati, A ;
Schühlen, H ;
Dibra, A ;
Dotzer, F ;
von Beckerath, N ;
Bollwein, H ;
Pache, J ;
Dirschinger, J ;
Berger, PP ;
Schömig, A .
CIRCULATION, 2004, 110 (24) :3627-3635