title: Relation Between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.
abstract: Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation.
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, Icahn School of Medicine at Mount Sinai, New York, New York; Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Giustino
authors.affiliation: Clinical Trials Center, 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: Clinical Trials Center, 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, Quebec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Généreux
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Usman
authors.initials: U
authors.lastname: Baber
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 and Angiology II, Universitats-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; Division of Cardiology, New York-Presbyterian Hospital, Columbia University Medical Center, New York, New York; Department of Cardiology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Giora
authors.initials: G
authors.lastname: Weisz
authors.affiliation: Clinical Trials Center, 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 & 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, First Health 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: Interventional Cardiovascular Research and Clinical Trials, 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: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Francese
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
authors.forename: Claire
authors.initials: C
authors.lastname: Litherland
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, 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; 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; D001792:Blood Platelets / Q000502:physiology*; D002423:Cause of Death / Q000639:trends; D003328:Coronary Thrombosis / Q000097:blood* / Q000453:epidemiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010976:Platelet Count; D019106:Postoperative Hemorrhage / Q000097:blood* / Q000139:chemically induced / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D010975:Platelet Aggregation Inhibitors