title: Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study.
abstract: BACKGROUND
  The antiplatelet effects of the Platelet Inhibition and Patient Outcomes (PLATO) trial dose of ticagrelor in patients nonresponsive to clopidogrel and after they switch agents are unknown.
  
  
  RESULTS
  Patients with stable coronary artery disease on aspirin therapy received a 300-mg clopidogrel load; nonresponders were identified by light transmittance aggregometry. In a 2-way crossover design, nonresponders (n=41) and responders (n=57) randomly received clopidogrel (600 mg/75 mg once daily) or ticagrelor (180 mg/90 mg twice daily) for 14 days during period 1. In period 2, all nonresponders switched treatment; half of the responders continued the same treatment, whereas the others switched treatment. Inhibition of platelet aggregation was higher in nonresponders treated with ticagrelor compared with clopidogrel (P<0.05). Treatment with ticagrelor among nonresponders resulted in a >10%, >30%, and >50% decrease in platelet aggregation from baseline in 100%, 75%, and 13% of patients, respectively. Platelet aggregation fell from 59+/-9% to 35+/-11% in patients switched from clopidogrel to ticagrelor and increased from 36+/-14% to 56+/-9% in patients switched from ticagrelor to clopidogrel (P<0.0001 for both). Platelet reactivity was below the cut points previously associated with ischemic risk measured by light transmittance aggregometry, VerifyNow P2Y(12) assay, and vasodilator-stimulated phosphoprotein phosphorylation in 98% to 100% of patients after ticagrelor therapy versus 44% to 76% of patients after clopidogrel therapy.
  
  
  CONCLUSIONS
  Ticagrelor therapy overcomes nonresponsiveness to clopidogrel, and its antiplatelet effect is the same in responders and nonresponders. Nearly all clopidogrel nonresponders and responders treated with ticagrelor will have platelet reactivity below the cut points associated with ischemic risk. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00642811.
authors.affiliation: Sinai Center for Thrombosis Research, Cardiac Catheterization Laboratory, Baltimore, MD 21215, USA. pgurbel@lifebridgehealth.org
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bliden
authors.forename: Kathleen
authors.initials: K
authors.lastname: Butler
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Antonino
authors.forename: Cheryl
authors.initials: C
authors.lastname: Wei
authors.forename: Renli
authors.initials: R
authors.lastname: Teng
authors.forename: Lars
authors.initials: L
authors.lastname: Rasmussen
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Tonny
authors.initials: T
authors.lastname: Nielsen
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Georges
authors.initials: G
authors.lastname: Sabe-Affaki
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: David
authors.initials: D
authors.lastname: Henderson
authors.forename: Dharmendra V
authors.initials: DV
authors.lastname: Patel
authors.forename: Udaya S
authors.initials: US
authors.lastname: Tantry
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine