title: Incidence, prognostic impact, and influence of antithrombotic therapy on access and nonaccess site bleeding in percutaneous coronary intervention.
abstract: OBJECTIVE
  The aim of this study was to evaluate the relative frequency of access and nonaccess site bleeding, the association of these events with 1-year mortality, and the impact of randomized antithrombotic therapy.
  
  
  BACKGROUND
  Post-percutaneous coronary intervention (PCI) bleeding has been strongly associated with subsequent mortality. The extent to which access versus nonaccess site bleeding contributes to this poor prognosis and the role of antithrombotic therapies remains poorly understood.
  
  
  METHODS
  The incidence and impact of Thrombolysis In Myocardial Infarction (TIMI) major/minor 30-day bleeding and randomized antithrombotic therapy were examined in a combined dataset from the REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events), Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY), and HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trials in 17,393 PCI patients.
  
  
  RESULTS
  The TIMI major/minor bleeding occurred in 5.3% of patients, 61.4% of which (3.3%) were nonaccess site bleeds. After multivariable adjustment, TIMI bleeding was associated with an increased risk of 1-year mortality (hazard ratio [HR]: 3.17, 95% confidence interval [CI]: 2.51 to 4.00, p < 0.0001). The HR of a nonaccess site bleed was approximately 2-fold that of an access site bleed: HR: 3.94, 95% CI: 3.07 to 5.15, p < 0.0001 versus HR: 1.82, 95% CI: 1.17 to 2.83, p = 0.008, respectively. Randomization to bivalirudin versus heparin + a glycoprotein IIb/IIIa inhibitor resulted in 38% and 43% relative reductions in TIMI major/minor and TIMI major bleeding, respectively (p < 0.0001 for both), with significant reductions in both access and nonaccess site bleeding.
  
  
  CONCLUSIONS
  Nonaccess site bleeding after PCI is common, representing approximately two-thirds of all TIMI bleeding events, and is associated with a 4-fold increase in 1-year mortality. Use of bivalirudin rather than heparin + a glycoprotein IIb/IIIa inhibitor significantly decreases both nonaccess site as well as access site bleeding events by approximately 40%.
authors.affiliation: Radboud University Medical Centre, Nijmegen, the Netherlands. f.w.a.verheugt@olvg.nl
authors.forename: Freek W A
authors.initials: FW
authors.lastname: Verheugt
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl
authors.forename: Martial
authors.initials: M
authors.lastname: Hamon
authors.forename: Harald
authors.initials: H
authors.lastname: Darius
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
authors.forename: Steven P
authors.initials: SP
authors.lastname: Marso
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Rao
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Gershlick
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000401:mortality; D000925:Anticoagulants / Q000009:adverse effects; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects*; D006470:Hemorrhage / Q000209:etiology* / Q000401:mortality; D006493:Heparin / Q000009:adverse effects; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D016016:Proportional Hazards Models; D011677:Punctures; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin