title: Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes.
abstract: Bleeding is a complication of current therapies for acute coronary syndrome (ACS). No studies have examined the effect of bleeding events on clinical outcomes. We analyzed pooled data from 4 multicenter, randomized clinical trials of patients who had ACS (n = 26,452) to determine an association between bleeding severity as measured by the GUSTO scale and 30-day and 6-month mortality rates using Cox proportional hazards modeling that incorporated bleeding as a time-dependent covariate. The analysis was repeated to examine procedure- and non-procedure-related bleeding and after censoring at the time of coronary artery bypass grafting. Of all the patients included, 27.6% had > or =1 bleeding episode. Patients who bled were older and sicker at presentation than were those who did not bleed. Unadjusted rates of 30-day and 6-month mortality increased as bleeding severity increased. There were stepwise increases in the adjusted hazards of 30-day mortality (mild bleeding, hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3 to 1.9; moderate bleeding, HR 2.7, 95% CI l 2.3 to 3.4; severe bleeding, HR 10.6, 95% CI 8.3 to 13.6) and 6-month mortality (mild bleeding, HR 1.4, 95% CI 1.2 to 1.6; moderate bleeding, HR 2.1, 95% CI 1.8 to 2.4; severe bleeding, HR 7.5, 95% CI 6.1 to 9.3) as bleeding severity increased. Results were consistent after censoring for coronary artery bypass grafting and for procedure- and non-procedure-related bleeds. In conclusion, the GUSTO bleeding classification identifies patients who are at risk for short- and long-term adverse events. Therapies that minimize bleeding risk and maintain an anticoagulant effect may improve outcomes among patients who have ACS.
authors.affiliation: The Duke Clinical Research Institute, Durham, North Carolina, USA. sunil.rao@duke.edu
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Rao
authors.forename: Kristi
authors.initials: K
authors.lastname: O'Grady
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pieper
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
mesh_terms: D000208:Acute Disease; D000368:Aged; D016001:Confidence Intervals; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012720:Severity of Illness Index; D015996:Survival Rate / Q000639:trends; D013577:Syndrome
chemical_list: D005343:Fibrinolytic Agents