The time dependence of antithrombin initiation in patients with non-ST-segment elevation acute coronary syndromes: subgroup analysis from the ACUITY trial.
OBJECTIVE
Antithrombins are among standard treatment agents for patients with non-ST-segment elevation acute coronary syndromes. We aimed to determine the association between time from emergency department (ED) presentation to treatment with an antithrombin and adverse cardiac events.


METHODS
The study cohort was a subgroup of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, enrolled from March 1, 2005, to December 5, 2005. The ACUITY trial enrolled patients with moderate- and high-risk non-ST-segment elevation acute coronary syndromes and who were undergoing an early invasive strategy (<72 hours from randomization). All patients received an antithrombin (unfractionated heparin, low-molecular-weight heparin, or bivalirudin), in addition to other agents. A formal ED case report form was introduced in March 2005. Time from presentation to antithrombin initiation was evaluated as a continuous variable in hours. The endpoints were defined as major ischemic events (death, myocardial infarction, unplanned revascularization) or major bleeding within 30 days, or inhospital major bleeding. Logistic regression was used to adjust for demographics, severity of disease, comorbidities, and treatment differences.


RESULTS
Of the 2,722 patients enrolled with an ED case report form, complete time data were available in 2,632 (96%). Median time to antithrombin administration was 4.87 hours (interquartile range 2.67 to 9.83). After multivariable analysis, there was no association of major ischemic events with log time (hours) to antithrombin treatment (adjusted odds ratio [OR] 0.99; 95% confidence interval [CI] 0.97 to 1.01). There was an increase in major bleeding at 30 days and inhospital major bleeding complications with longer log time (hours) to antithrombin initiation (adjusted OR 1.44, 95% CI 1.15 to 1.80; OR 1.43, 95% CI 1.13 to 1.83, respectively).


CONCLUSIONS
In this study of patients with non-ST-segment elevation acute coronary syndromes who were undergoing an early invasive management strategy, we were unable to demonstrate an association between adverse ischemic outcomes with the timing of antithrombin administration. However, there was an increase in bleeding outcomes as time to antithrombin administration increased.
Diercks
Deborah B
DB
University of California, Davis Medical Center, Sacramento, CA, USA. dbdiercks@ucdavis.edu
Pollack
Charles V
CV
Hollander
Judd E
JE
Blomkalns
Andra L
AL
Emerman
Charles L
CL
Rokos
Ivan C
IC
Larson
David M
DM
Hoekstra
James W
JW
Mehran
Roxana
R
Stone
Gregg W
GW
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016001:Confidence Intervals; D004636:Emergency Service, Hospital; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006629:Hirudins / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D017202:Myocardial Ischemia / Q000517:prevention & control; D016017:Odds Ratio; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D013997:Time Factors
D000991:Antithrombins; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin