title: Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials.
abstract: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose.
  
  
  
  A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk.
  
  
  
  The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61-0·85) in the derivation cohort, and 0·70 (0·65-0·74) in the PLATO trial validation cohort and 0·66 (0·61-0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction=0·007), and exerted a significant ischaemic benefit only in this latter group.
  
  
  
  The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration.
  
  
  
  None.
authors.affiliation: Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland; Erasmus University Medical Center, Rotterdam, Netherlands; Department of Clinical and Experimental Medicine, Policlinic "G Martino", University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Costa
authors.affiliation: Erasmus University Medical Center, Rotterdam, Netherlands; Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: van Klaveren
authors.affiliation: Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: James
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Dik
authors.initials: D
authors.lastname: Heg
authors.affiliation: Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Räber
authors.affiliation: Istituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil.
authors.forename: Fausto
authors.initials: F
authors.lastname: Feres
authors.affiliation: Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pilgrim
authors.affiliation: Severance Cardiovascular Hospital, Yonsei University College of Medicine and Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Myeong-Ki
authors.initials: MK
authors.lastname: Hong
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: EMO-GVM Centro Cuore Columbus, Milan, Italy; Interventional Cardiology Department, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Colombo
authors.affiliation: Department of Cardiology, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, Paris, France.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zanchin
authors.affiliation: Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Bologna, Italy.
authors.forename: Tullio
authors.initials: T
authors.lastname: Palmerini
authors.affiliation: Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.affiliation: Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.affiliation: Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.affiliation: Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland; Erasmus University Medical Center, Rotterdam, Netherlands. Electronic address: marco.valgimigli@insel.ch.
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000009:adverse effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000401:mortality / Q000601:surgery*; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment / Q000379:methods; D015607:Stents; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin