title: Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.
abstract: Anemic patients remain at increased risk of ischemic and bleeding events. Whether the effects of hemoglobin levels on thrombotic and bleeding risk are independent of platelet reactivity on clopidogrel, however, remains unknown. Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were categorized by the presence of anemia at baseline, defined according the World Health Organization criteria. Platelet reactivity was measured with VerifyNow assay; high platelet reactivity (HPR) on clopidogrel was defined as platelet reactive units value >208. Of 8,413 patients included in the study cohort, 1,816 (21.6%) had anemia. HPR was more prevalent in patients with anemia (58.3% vs 38.4%; p <0.001), an association that persisted after multivariate adjustment (adjusted odds ratio: 2.04; 95% confidence interval [CI]: 1.82 to 2.29; p <0.0001). Patients with anemia had higher 2-year rates of major adverse cardiac events (9.5% vs 5.6%; p <0.0001), major bleeding (11.8% vs 7.7%; p <0.0001), and all-cause mortality (4.0% vs 1.4%; p <0.0001); however, after adjustment for baseline clinical confounders, including HPR, anemia was no longer significantly associated with major adverse cardiac events but was still independently associated with all-cause mortality (adjusted HR 1.61, 95% CI 1.23 to 2.12; p <0.0001) and major bleeding (adjusted HR 1.42, 95% CI 1.20 to 1.68; p <0.0001). The effect of HPR on clinical outcomes was uniform according to anemia status, without evidence of interaction. In conclusion, anemia independently correlated with HPR. After percutaneous coronary intervention with drug-eluting stents, anemia at baseline was significantly associated with higher 2-year hemorrhagic and mortality risk; conversely, its association with ischemic risk was attenuated after multivariate adjustment, including HPR.
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, The Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Giustino
authors.affiliation: Cardiovascular Research Foundation, New York, New York; Division of Cardiology, New York-Presbyterian Hospital, Columbia University Medical Center, New York, New York.
authors.forename: Ajay J
authors.initials: AJ
authors.lastname: Kirtane
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, The Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Usman
authors.initials: U
authors.lastname: Baber
authors.affiliation: Cardiovascular Research Foundation, New York, New York; Division of Cardiology, New York-Presbyterian Hospital, Columbia University Medical Center, New York, New York; Division of Cardiology, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Généreux
authors.affiliation: Department of Cardiology and Pneumology, Helios Amper-Klinikum, Dachau, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Witzenbichler
authors.affiliation: Department of Cardiology, Universitats-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.affiliation: Cardiovascular Research Foundation, New York, New York; Division of Cardiology, New York-Presbyterian Hospital, Columbia University Medical Center, New York, New York; Department of Medicine, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Giora
authors.initials: G
authors.lastname: Weisz
authors.affiliation: Cardiovascular Research Foundation, New York, New York; Division of Cardiology, New York-Presbyterian Hospital, Columbia University Medical Center, New York, New York.
authors.forename: Akiko
authors.initials: A
authors.lastname: Maehara
authors.affiliation: Sanger Heart and Vascular Institute, Carolinas HealthCare System, Charlotte, North Carolina.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rinaldi
authors.affiliation: Wellmont CVA Heart Institute, Kingsport, Tennessee.
authors.forename: Christopher
authors.initials: C
authors.lastname: Metzger
authors.affiliation: Department of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California; Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.affiliation: Department of Medicine, 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: Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Ernest L
authors.initials: EL
authors.lastname: Mazzaferri
authors.affiliation: Department of Cardiology, Cone Health, LeBauer Cardiovascular Research Foundation, Greensboro, North Carolina.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Brodie
authors.affiliation: Department of Cardiology, Cone Health, LeBauer Cardiovascular Research Foundation, Greensboro, North Carolina.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Stuckey
authors.affiliation: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Falls Church, Virginia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, The Icahn School of Medicine at Mount Sinai, New York, New York; Cardiovascular Research Foundation, New York, New York.
authors.forename: George D
authors.initials: GD
authors.lastname: Dangas
authors.affiliation: Cardiovascular Research Foundation, New York, New York.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Francese
authors.affiliation: Cardiovascular Research Foundation, New York, New York.
authors.forename: Ozgu
authors.initials: O
authors.lastname: Ozan
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, The Icahn School of Medicine at Mount Sinai, New York, New York; Cardiovascular Research Foundation, New York, New York.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Cardiovascular Research Foundation, New York, New York; Division of Cardiology, New York-Presbyterian Hospital, Columbia University Medical Center, New York, New York. Electronic address: gstone@crf.org.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D000368:Aged; D000740:Anemia / Q000150:complications*; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000150:complications / Q000601:surgery*; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005060:Europe / Q000453:epidemiology; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014481:United States / Q000453:epidemiology
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin