title: Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention.
abstract: OBJECTIVE
  Dual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia but increases bleeding.
  
  
  OBJECTIVE
  To develop a clinical decision tool to identify patients expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI.
  
  
  METHODS
  Among 11,648 randomized DAPT Study patients from 11 countries (August 2009-May 2014), a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014).
  
  
  METHODS
  Twelve months of open-label thienopyridine plus aspirin, then randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin.
  
  
  METHODS
  Ischemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI.
  
  
  RESULTS
  Among DAPT Study patients (derivation cohort; mean age, 61.3 years; women, 25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; -1 point for age 65 to younger than 75 years; and -2 points for age 75 years or older. Among the high score group (score ≥2, n = 5917), continued thienopyridine vs placebo was associated with reduced ischemic events (2.7% vs 5.7%; risk difference [RD], -3.0% [95% CI, -4.1% to -2.0%], P < .001) compared with the low score group (score <2, n = 5731; 1.7% vs 2.3%; RD, -0.7% [95% CI, -1.4% to 0.09%], P = .07; interaction P < .001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; RD, 0.4% [95% CI, -0.3% to 1.0%], P = .26) compared with the low score group (3.0% vs 1.4%; RD, 1.5% [95% CI, 0.8% to 2.3%], P < .001; interaction P = .02). Among PROTECT patients (validation cohort; mean age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n = 2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding.
  
  
  CONCLUSIONS
  Among patients not sustaining major bleeding or ischemic events 1 year after PCI, a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00977938.
authors.affiliation: Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts2Harvard Medical School, Boston, Massachusetts3Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Yeh
authors.affiliation: Harvard Medical School, Boston, Massachusetts3Harvard Clinical Research Institute, Boston, Massachusetts4Cardiology Division, Massachusetts General Hospital, Boston.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Secemsky
authors.affiliation: Christ Hospital Heart and Vascular Center, Cincinnati, Ohio6Lindner Center for Research and Education, Cincinnati, Ohio.
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.affiliation: Harvard Medical School, Boston, Massachusetts7Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Sharon-Lise T
authors.initials: SL
authors.lastname: Normand
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom9National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Gershlick
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, Missouri11University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
authors.forename: David J
authors.initials: DJ
authors.lastname: Cohen
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, Missouri11University of Missouri-Kansas City School of Medicine, Kansas City, Missouri12Washington University in St Louis, School of Medicine, St Louis, Missouri.
authors.forename: John A
authors.initials: JA
authors.lastname: Spertus
authors.affiliation: Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Paris, France14Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique, Hôpitaux de Paris, Paris, France15National Heart and Lung Institute, Institute of Card.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Harvard Medical School, Boston, Massachusetts3Harvard Clinical Research Institute, Boston, Massachusetts16Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Cutlip
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: Institut Loraine du Coeur et des Vaisseaux, University Hospital of Nancy-Brabois, Vandoeuvre-les-Nancy, France.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Camenzind
authors.affiliation: Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis Hospital, Aalst, Belgium.
authors.forename: William
authors.initials: W
authors.lastname: Wijns
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Apruzzese
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts20Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.affiliation: Harvard Medical School, Boston, Massachusetts3Harvard Clinical Research Institute, Boston, Massachusetts21Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Laura
authors.initials: L
authors.lastname: Mauri
mesh_terms: D000367:Age Factors; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D003920:Diabetes Mellitus; D054855:Drug-Eluting Stents; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D007511:Ischemia / Q000453:epidemiology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D017239:Paclitaxel / Q000008:administration & dosage; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013927:Thrombosis / Q000453:epidemiology*; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C446540:thienopyridine; D017239:Paclitaxel; D001241:Aspirin