title: Association of spontaneous and procedure-related bleeds with short- and long-term mortality after acute coronary syndromes: an analysis from the PLATO trial.
abstract: OBJECTIVE
  We sought to describe the differential effect of bleeding events in acute coronary syndromes (ACS) on short- and long-term mortality according to their type and severity.
  
  
  RESULTS
  The PLATO trial randomised 18,624 ACS patients to clopidogrel or ticagrelor. Post-randomisation bleeding events were captured according to bleeding type (spontaneous or procedure-related), with PLATO, TIMI, and GUSTO definitions. The association of bleeding events with subsequent short-term (<30 days) and long-term (>30 days) all-cause mortality was assessed using time-dependent Cox proportional hazard models. A model was fitted to compare major and minor bleeding for mortality prediction. Of 18,624 patients, 2,189 (11.8%) had at least one PLATO major bleed (mean follow-up 272.2±123.5 days). Major bleeding was associated with higher short-term mortality (adjusted hazard ratio [HR] 9.28; 95% confidence interval [CI]: 7.50-11.48) but not with long-term mortality (adjusted HR 1.28; 95% CI: 0.93-1.75). Spontaneous bleeding was associated with short-term (adjusted HR 14.59; 95% CI: 11.14-19.11) and long-term (adjusted HR 3.38; 95% CI: 2.26-5.05) mortality. Procedure-related bleeding was associated with short-term mortality (adjusted HR 5.29; 95% CI: 4.06-6.87): CABG-related and non-coronary-procedure-related bleeding were associated with a higher short-term mortality, whereas PCI or angiography-related bleeding was not associated with either short- or long-term mortality. Similar results were obtained using the GUSTO and TIMI bleeding definitions.
  
  
  CONCLUSIONS
  Major bleeding is associated with high subsequent mortality in ACS. However, this association is much stronger in the first 30 days and is strongest for spontaneous (vs. procedure-related) bleeding.
authors.affiliation: Département Hospitalo-Universitaire FIRE, AP-HP, Hôpital Bichat, Paris, France.
authors.forename: Gregory
authors.initials: G
authors.lastname: Ducrocq
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Schulte
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.forename: Anders
authors.initials: A
authors.lastname: Himmelmann
authors.forename: Riitta
authors.initials: R
authors.lastname: Lassila
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Sorbets
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
mesh_terms: D054058:Acute Coronary Syndrome / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives; D000368:Aged; D000077144:Clopidogrel; D017023:Coronary Angiography / Q000009:adverse effects*; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000401:mortality; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine