title: Impact of Hemoglobin A1c Levels on Residual Platelet Reactivity and Outcomes After Insertion of Coronary Drug-Eluting Stents (from the ADAPT-DES Study).
abstract: An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether HbA1c levels are associated with high platelet reactivity (HPR) in patients loaded with clopidogrel and aspirin, thereby constituting an argument for intensified antiplatelet therapy in patients with poor glycemic control. In the prospective, multicenter Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c <6.5% (n = 551, 48.12%), 6.5% to 8.5% (n = 423, 36.9%), and >8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208 and aspirin reaction units >550, respectively. HPR on clopidogrel was frequent (48.3%), whereas HPR on aspirin was not (3.9%). Patients with HbA1c >8.5% were younger, more likely non-Caucasian, had a greater body mass index, and more insulin-treated diabetes and acute coronary syndromes. Proportions of PRU >208 (42.5%, 50.2%, and 62.3%, p <0.001) and rates of definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models that included PRU, high HbA1c levels (>8.5) remained associated with ST (hazard ratio 3.92, 95% CI 1.29 to 12.66, p = 0.02) and cardiac death (hazard ratio 4.24, 95% CI 1.41 to 12.70) but not bleeding at 2-year follow-up. There was no association between aspirin reaction units >550 and HbA1c levels. In conclusion, in this large-scale study, HbA1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control, which predicted ST and cardiac death after PCI regardless of PRU levels, warranting efforts to improve glycemic control after DES implantation in patients with diabetes mellitus.
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel M
authors.initials: MM
authors.lastname: Schoos
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
authors.forename: George D
authors.initials: GD
authors.lastname: Dangas
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; Center for Interventional Vascular Therapy, Division of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York.
authors.forename: Ajay J
authors.initials: AJ
authors.lastname: Kirtane
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Prince of Wales Clinical School, Randwick, New South Wales, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yu
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
authors.forename: Claire
authors.initials: C
authors.lastname: Litherland
authors.affiliation: Department of Cardiology, Nykoebing F Hospital, Institute of Regional Health Research, University of Southern Denmark, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Clemmensen
authors.affiliation: LeBauer Cardiovascular Research Foundation/Cone Health, Greensboro, North Carolina.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Stuckey
authors.affiliation: Department of Cardiology and Pneumology, Helios Amper-Klinikum, Dachau, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Witzenbichler
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; Center for Interventional Vascular Therapy, Division of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York; Els & Charles Bendheim Department of Cardiology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Giora
authors.initials: G
authors.lastname: Weisz
authors.affiliation: Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, North Carolina.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rinaldi
authors.affiliation: Department of Cardiology and Angiology II, Universitäts-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.affiliation: Wellmont CVA Heart Institute, Kingsport, Tennessee.
authors.forename: D Christopher
authors.initials: DC
authors.lastname: Metzger
authors.affiliation: Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota; Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.affiliation: Lehigh Valley Health Network, Allentown, Pennsylvania.
authors.forename: David A
authors.initials: DA
authors.lastname: Cox
authors.affiliation: Reid Heart Center, FirstHealth of the Carolinas, Pinehurst, North Carolina.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Duffy
authors.affiliation: LeBauer Cardiovascular Research Foundation/Cone Health, Greensboro, North Carolina.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Brodie
authors.affiliation: The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Ernest L
authors.initials: EL
authors.lastname: Mazzaferri
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; Center for Interventional Vascular Therapy, Division of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York.
authors.forename: Akiko
authors.initials: A
authors.lastname: Maehara
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; Center for Interventional Vascular Therapy, Division of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York. Electronic address: gs2184@columbia.edu.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000628:therapy*; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003920:Diabetes Mellitus / Q000097:blood*; D054855:Drug-Eluting Stents; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011446:Prospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000077144:Clopidogrel; D006442:Glycated Hemoglobin; D010975:Platelet Aggregation Inhibitors; D013988:Ticlopidine