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 drugeluting 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. Findings 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). Interpretation 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.
Bibliographical noteFunding Information:
GWS has served as a consultant for Osprey, Reva, Merck, Boston Scientific, Abbott Vascular, AstraZeneca, Eli Lilly-Daiichi Sankyo partnership, Bristol-Myers Squibb-Sanofi partnership, Otsuka, The Medicines Company, Ortho-McNeil, Gilead, InspireMD, TherOx, Atrium, Volcano, InfraReDx, Medtronic, Genentech, GlaxoSmithKline, Miracor, MPP Group, Lutonix, Velomedix, CSI, AGA, and Thoratec; has received honoraria from Edwards and Vascular Solutions; and has hold stock or options from CoreValve, Biostar I and II funds, MedFocus I, II, and Accelerator funds, Caliber, Flowcardia, Guided Delivery Systems, Arstasis, Micardia, Access Closure, Embrella and VNT. BW has received lecture honoraria from Volcano Corp, Boston Scientific, and Abbott Vascular. GW has been a board member on Bloxr; has served as a consultant for Tryton, Bloxr, Infraredx, Phillips, Svelte, Sync-Rx, Simbionix; and his wife holds a patent and stock options in MGVS. F-JN has served as a consultant for Eli Lilly, Daiichi Sankyo, and AstraZeneca; has received grants from Eli Lilly, Daiichi Sankyo, AstraZeneca, The Medicines Company, Boston Scientific, Medtronic, Cordis, and Roche Pharma; and has received speaker fees from Eli Lilly, Daiichi Sankyo, AstraZeneca, The Medicines Company, Biotronik, Boston Scientific, and Medtronic. CM has served as a consultant for Abbott Vascular and The Medicines Company; and has received honoraria from Abbott Vascular and speaker fees from The Medicines Company. DAC has served as a consultant for Abbott Vascular, Boston Scientific, and The Medicines Company. PAG has served as a consultant to Daiichi Sankyo, Lilly, Boehringer Ingleheim, Merck, Medtronic, Iverson Genetics, Pozen, Novartis, Bayer, Astrazeneca, Accumetrics, Nanosphere, Sanofi-Aventis, CSL, and Hemonetics; has received grants from NIH, Daiichi Sankyo/Lilly, Pozen, CSL, Astra Zeneca, Sanofi-Aventis, Haemoscope, HCRI, and DCRI; has received lecture honoraria from Lilly/ Daiichi Sankyo; has received payment for preparation of educational presentations from Schering Plough, Discovery Channel, Primed; and has stock or stock options from Merck, Pfizer, and Medtronic. RM has served as a consultant for AstraZeneca, Janssen (Johnson & Johnson), Regado, Abbott, Merck, Maya Medical; and has received grants from Sanofi/BMS, The Medicines Co, and Lilly/Daiichi Sankyo. TDS has received honoraria and lecture fees from Boston Scientific. The other authors declare they have no conflicts of interest.
The study was sponsored by the Cardiovascular Research Foundation, New York, NY, USA, under a US Food and Drug Administration investigational device exemption. The study was funded by research grants from Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics.