Platelet Reactivity and Cardiovascular Outcomes After Percutaneous Coronary Intervention A Time-Dependent Analysis of the Gauging Responsiveness With a VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) Trial

被引:354
作者
Price, Matthew J. [1 ,2 ]
Angiolillo, Dominick J. [3 ]
Teirstein, Paul S. [1 ,2 ]
Lillie, Elizabeth [1 ,2 ]
Manoukian, Steven V. [4 ,5 ]
Berger, Peter B. [6 ]
Tanguay, Jean-Francois [7 ]
Cannon, Christopher P. [8 ]
Topol, Eric J. [1 ,2 ]
机构
[1] Scripps Clin, La Jolla, CA 92037 USA
[2] Scripps Translat Sci Inst, La Jolla, CA USA
[3] Univ Florida, Coll Med, Jacksonville, FL USA
[4] Sarah Cannon Res Inst, Nashville, TN USA
[5] Hosp Corp Amer, Nashville, TN USA
[6] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA
[7] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada
[8] Brigham & Womens Hosp, Boston, MA 02115 USA
关键词
clopidogrel; platelets; randomized controlled trial; stent thrombosis; thrombosis; OF-CARE ASSAY; DOSE CLOPIDOGREL; ANTIPLATELET THERAPY; INHIBITION; AGGREGATION; VARIABILITY; RESISTANCE; PRASUGREL; STANDARD; EVENTS;
D O I
10.1161/CIRCULATIONAHA.111.029165
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-In the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial, 6 months of high-dose clopidogrel did not reduce cardiovascular events compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity (OTR) after percutaneous coronary intervention, defined as OTR >= 230 P2Y12 reaction units according to the VerifyNow P2Y12 platelet function test. The aim of this analysis was to examine the relationship between outcomes and OTR over the course of the trial. Methods and Results-OTR was measured at 12 to 24 hours and 30 +/- 7 days after percutaneous coronary intervention. Cox proportional hazards models with OTR as a time-varying covariate were used to determine the association between OTR and the primary end point of cardiovascular death, myocardial infarction, and stent thrombosis. Of the 2800 enrolled patients, 2796 (99.98%) had evaluable platelet function data. OTR <208 P2Y12 reaction units was significantly associated with a lower risk of the primary end point at 60 days (hazard ratio, 0.18; 95% confidence interval, 0.04 to 0.79; P = 0.02) and at 6 months (hazard ratio, 0.43; 95% confidence interval, 0.23 to 0.82; P = 0.01). After adjustment for other significant predictors of outcome, OTR <208 P2Y12 reaction units remained independently associated with the primary end point at 60 days (hazard ratio, 0.23; 95% confidence interval, 0.05 to 0.98; P = 0.047) and tended to be associated at 6 months (adjusted hazard ratio, 0.54; 95% confidence interval, 0.28 to 1.04; P = 0.065). Conclusions-In the GRAVITAS trial, achievement of on-clopidogrel reactivity <208 P2Y12 reaction units at 12 to 24 hours after percutaneous coronary intervention or during follow-up was associated with a lower risk for cardiovascular events. The efficacy of an individualized strategy to target a level of OTR below this threshold merits investigation.
引用
收藏
页码:1132 / 1137
页数:6
相关论文
共 36 条
  • [1] Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment
    Airoldi, Flavio
    Colombo, Antonio
    Morici, Nuccia
    Latib, Azeem
    Cosgrave, John
    Buellesfeld, Lutz
    Bonizzoni, Erminio
    Carlino, Mauro
    Gerckens, Ulrich
    Godino, Cosmo
    Melzi, Gloria
    Michev, Iassen
    Montorfano, Matteo
    Sangiorgi, Giuseppe Massimo
    Qasim, Asif
    Chieffo, Alaide
    Briguori, Carlo
    Grube, Eberhard
    [J]. CIRCULATION, 2007, 116 (07) : 745 - 754
  • [2] Clopidogrel 150 mg/day to Overcome Low Responsiveness in Patients Undergoing Elective Percutaneous Coronary Intervention Results From the VASP-02 (Vasodilator-Stimulated Phosphoprotein-02) Randomized Study
    Aleil, Boris
    Jacquemin, Laurent
    De Poli, Fabien
    Zaehringer, Michel
    Collet, Jean-Philippe
    Montalescot, Gilles
    Cazenave, Jean-Pierre
    Dickele, Marie-Claude
    Monassier, Jean-Pierre
    Gachet, Christian
    [J]. JACC-CARDIOVASCULAR INTERVENTIONS, 2008, 1 (06) : 631 - 638
  • [3] Functional effects of high Clopidogrel maintenance dosing in patients with inadequate platelet inhibition on standard dose treatment
    Angiolillo, Dominick J.
    Costa, Marco A.
    Shoemaker, Steven B.
    Desai, Bhaloo
    Bernardo, Esther
    Suzuki, Yoshie
    Charlton, Ronald K.
    Zenni, Martin M.
    Guzman, Luis A.
    Bass, Theodore A.
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 2008, 101 (04) : 440 - 445
  • [4] Functional impact of high clopidogrel maintenance dosing in patients undergoing elective percutaneous coronary interventions -: Results of a randomized study
    Angiolillo, Dominick J.
    Bernardo, Esther
    Palazuelos, Jorge
    Desai, Bhaloo
    Weisberg, Ian
    Alfonso, Fernando
    Guzman, Luis A.
    Hernandez-Antolin, Rosana
    Zenni, Martin Z.
    Macaya, Carlos
    Fernandez-Ortiz, Antonio
    Bass, Theodore A.
    [J]. THROMBOSIS AND HAEMOSTASIS, 2008, 99 (01) : 161 - 168
  • [5] Variability in individual responsiveness to clopidogrel - Clinical implications, management, and future perspectives
    Angiolillo, Dominick J.
    Fernandez-Ortiz, Antonio
    Bernardo, Esther
    Alfonso, Fernando
    Macaya, Carlos
    Bass, Theodore A.
    Costa, Marco A.
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 49 (14) : 1505 - 1516
  • [6] Increased Platelet Inhibition After Switching From Maintenance Clopidogrel to Prasugrel in Patients With Acute Coronary Syndromes Results of the SWAP (SWitching Anti Platelet) Study
    Angiolillo, Dominick J.
    Saucedo, Jorge F.
    DeRaad, Roger
    Frelinger, Andrew L.
    Gurbel, Paul A.
    Costigan, Timothy M.
    Jakubowski, Joseph A.
    Ojeh, Clement K.
    Effron, Mark B.
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2010, 56 (13) : 1017 - 1023
  • [7] Pilot Study of the Antiplatelet Effect of Increased Clopidogrel Maintenance Dosing and Its Relationship to CYP2C19 Genotype in Patients With High On-Treatment Reactivity
    Barker, Colin M.
    Murray, Sarah S.
    Teirstein, Paul S.
    Kandzari, David E.
    Topol, Eric J.
    Price, Matthew J.
    [J]. JACC-CARDIOVASCULAR INTERVENTIONS, 2010, 3 (10) : 1001 - 1007
  • [8] Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: A multicenter randomized prospective study
    Bonello, Laurent
    Camoin-Jau, Laurence
    Arques, Stephane
    Boyer, Christian
    Panagides, Dimitri
    Wittenberg, Olivier
    Simeoni, Marie-Claude
    Barragan, Paul
    Dignat-George, Francoise
    Paganelli, Franck
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2008, 51 (14) : 1404 - 1411
  • [9] Consensus and Future Directions on the Definition of High On-Treatment Platelet Reactivity to Adenosine Diphosphate
    Bonello, Laurent
    Tantry, Udaya S.
    Marcucci, Rossella
    Blindt, Ruediger
    Angiolillo, Dominick J.
    Becker, Richard
    Bhatt, Deepak L.
    Cattaneo, Marco
    Collet, Jean Philippe
    Cuisset, Thomas
    Gachet, Christian
    Montalescot, Gilles
    Jennings, Lisa K.
    Kereiakes, Dean
    Sibbing, Dirk
    Trenk, Dietmar
    Van Werkum, Jochem W.
    Paganelli, Franck
    Price, Matthew J.
    Waksman, Ron
    Gurbel, Paul A.
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2010, 56 (12) : 919 - 933
  • [10] Tailored Clopidogrel Loading Dose According to Platelet Reactivity Monitoring to Prevent Acute and Subacute Stent Thrombosis
    Bonello, Laurent
    Camoin-Jau, Laurence
    Armero, Sebastien
    Com, Olivier
    Arques, Stephane
    Burignat-Bonello, Caroline
    Giacomoni, Marie-Paule
    Bonello, Roland
    Collet, Frederic
    Rossi, Philippe
    Barragan, Paul
    Dignat-George, Francoise
    Paganelli, Franck
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 2009, 103 (01) : 5 - 10