title: Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study.
abstract: BACKGROUND
  The relation between platelet reactivity and stent thrombosis, major bleeding, and other adverse events after coronary artery implantation of drug-eluting stents has been incompletely characterised. We aimed to determine the relation between platelet reactivity during dual therapy with aspirin and clopidogrel and clinical outcomes after successful coronary drug-eluting stent implantation.
  
  
  METHODS
  ADAPT-DES was a prospective, multicentre registry of patients successfully treated with one or more drug-eluting stents and given aspirin and clopidogrel at 10-15 US and European hospitals. We assessed platelet reactivity in those patients after successful percutaneous coronary intervention using VerifyNow point-of-care assays, and assigned different cutoffs to define high platelet reactivity. The primary endpoint was definite or probable stent thrombosis; other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. We did a propensity-adjusted multivariable analysis to determine the relation between platelet reactivity and subsequent adverse events. This study is registered with ClinicalTrials.gov, number NCT00638794.
  
  
  RESULTS
  Between Jan 7, 2008, and Sept 16, 2010, 8665 patients were prospectively enrolled at 11 sites, of which 8583 were eligible. At 1-year follow-up, stent thrombosis had occurred in 70 (0·8%) patients, myocardial infarction in 269 (3·1%), clinically relevant bleeding in 531 (6·2%), and death in 161 (1·9%) patients. High platelet reactivity on clopidogrel was strongly related to stent thrombosis (adjusted HR 2·49 [95% CI 1·43-4·31], p=0·001) and myocardial infarction (adjusted HR 1·42 [1·09-1·86], p=0·01), was inversely related to bleeding (adjusted HR 0·73 [0·61-0·89], p=0·002), but was not related to mortality (adjusted HR 1·20 [0·85-1·70], p=0·30). High platelet reactivity on aspirin was not significantly associated with stent thrombosis (adjusted HR 1·46 [0·58-3·64], p=0·42), myocardial infarction, or death, but was inversely related to bleeding (adjusted HR 0·65 [0·43-0·99], p=0·04).
  
  
  CONCLUSIONS
  The findings from this study emphasise the counter-balancing effects of haemorrhagic and ischaemic complications after stent implantation, and suggest that safer drugs or tailored strategies for the use of more potent agents must be developed if the benefits of greater platelet inhibition in patients with cardiovascular disease are to be realised.
  
  
  BACKGROUND
  Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics.
authors.affiliation: Columbia University Medical Center, New York-Presbyterian Hospital, New York, NY 10022, USA. gs2184@columbia.edu
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.forename: Bernhard
authors.initials: B
authors.lastname: Witzenbichler
authors.forename: Giora
authors.initials: G
authors.lastname: Weisz
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rinaldi
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.forename: D Christopher
authors.initials: DC
authors.lastname: Metzger
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.forename: David A
authors.initials: DA
authors.lastname: Cox
authors.forename: Peter L
authors.initials: PL
authors.lastname: Duffy
authors.forename: Ernest
authors.initials: E
authors.lastname: Mazzaferri
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Helen
authors.initials: H
authors.lastname: Parise
authors.forename: Ajay J
authors.initials: AJ
authors.lastname: Kirtane
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Brodie
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Stuckey
mesh_terms: D001241:Aspirin / Q000627:therapeutic use; D001780:Blood Coagulation Tests; D000077144:Clopidogrel; D003327:Coronary Disease / Q000188:drug therapy / Q000601:surgery*; D023921:Coronary Stenosis / Q000209:etiology / Q000517:prevention & control; D054855:Drug-Eluting Stents / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000379:methods; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019095:Point-of-Care Systems; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin