title: Bleeding, mortality, and antiplatelet therapy: results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial.
abstract: BACKGROUND
  The association between bleeding severity and cause of mortality in the non-acute setting is unclear. We sought to investigate the association between bleeding and mortality subtype, and assess whether this association differs in patients on dual antiplatelet therapy (DAPT) versus aspirin alone.
  
  
  METHODS
  Using multivariable Cox proportional hazards survival regression, we examined the association between moderate or severe bleeding and all-cause, cardiovascular, and cancer mortality in 15,603 patients with cardiovascular disease or multiple risk factors enrolled in the CHARISMA trial.
  
  
  RESULTS
  Patients with moderate or severe bleeding had a higher incidence of all-cause, cardiovascular, and cancer mortality (P < .001 for each). After multivariable adjustment, moderate/severe bleeding remained independently associated with not only all-cause mortality (adjusted hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.24-2.21) and cardiovascular mortality (HR 2.05, 95% CI 1.38-3.04) but also cancer mortality (HR 4.76, 95% CI 2.60-8.69). However, there was a significant interaction between bleeding and potency of antiplatelet therapy for all-cause (P = .002), cardiovascular (P = .02), and cancer mortality (P = .03); in subjects on aspirin alone, moderate/severe bleeding was associated with all-cause (HR 5.27, 95% CI 3.56-7.80), cardiovascular (HR 4.33, 95% CI 2.55-7.37), and cancer mortality (HR 9.01, 95% CI 4.41-18.43), but not in subjects on DAPT (all-cause: HR 1.48, 95% CI 0.93-2.34; cardiovascular: HR 1.04, 95% CI 0.58-1.86; and cancer mortality: HR 1.79, 95% CI 0.56-5.74).
  
  
  CONCLUSIONS
  In stable patients, moderate or severe bleeding is associated with a significantly increased risk of all-cause, cardiovascular, and cancer mortality. However, this risk appeared different in subjects on single antiplatelet therapy versus DAPT.
authors: New York University School of Medicine, New York, NY, USA.
authors: Jeffrey S
authors: JS
authors: Berger
authors: Deepak L
authors: DL
authors: Bhatt
authors: P Gabriel
authors: PG
authors: Steg
authors: Steven R
authors: SR
authors: Steinhubl
authors: Gilles
authors: G
authors: Montalescot
authors: Mingyuan
authors: M
authors: Shao
authors: Werner
authors: W
authors: Hacke
authors: Keith A
authors: KA
authors: Fox
authors: Peter B
authors: PB
authors: Berger
authors: Eric J
authors: EJ
authors: Topol
authors: A Michael
authors: AM
authors: Lincoff
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000150:complications* / Q000188:drug therapy; D002423:Cause of Death / Q000639:trends; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D014943:Global Health; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine