Supplementary Table 1. Unadjusted and Adjusted Associations Between Treatment
Assignment and the Risk of Bleeding Before Coronary Angiography
Model
Hazard Ratio* (95% Confidence
Interval)
p-value
Unadjusted
Bivalirudin alone
0.94 (0.47-1.89)
0.87
Enoxaparin alone
1.28 (0.59-2.78)
0.53
Bivalirudin + GPI
3.84 (1.94-7.63)
<0.001
Unfractionated heparin + GPI
3.50 (1.66-7.37)
0.001
Enoxaparin + GPI
3.16 (1.55-6.42)
0.002
Bivalirudin alone
0.95 (0.47-1.90)
0.88
Enoxaparin alone
1.30 (0.60-2.82)
0.51
Bivalirudin + GPI
3.91 (1.97-7.77)
<0.001
Unfractionated heparin + GPI
3.40 (1.61-7.16)
0.001
Enoxaparin + GPI
3.16 (1.54-6.44)
0.002
Adjusted
Treatment assignment was included in a Cox proportional hazards model along with
the following covariates: age, sex, insulin-treated diabetes, current smoking, previous
percutaneous coronary intervention, previous coronary artery bypass graft surgery,
and weight. Time variable was time from randomization to bleeding or coronary
angiography (censored). Inclusion in the study was conditional on undergoing
coronary angiography.
*Reference: Heparin alone.
GPI = glycoprotein IIb/IIIa inhibitor
Supplemental Table 2A. Missing Data for Covariates Used in Multivariable Models
Variable
N missing/Total N
% Missing
Age
0/13,726
0.0%
Gender
0/13,726
0.0%
Insulin-treated DM
91/13,726
0.7%
Current Smoker
237/13,726
1.7%
Weight
14/13,726
0.1%
Previous PCI
117/13,726
0.9%
Previous CABG
26/13,726
0.2%
Renal insufficiency
835/13,726
6.0%
Biomarker positivity
1,059/13,726
7.7%
Heparin
0/13,726
0.0%
Bivalirudin
0/13,726
0.0%
CABG, coronary artery bypass grafting; DM, diabetes mellitus; PCI, percutaneous coronary
intervention
Supplemental Table 2B. Complete Case Analyses.
Outcome
Predictor variable
Hazard ratio
p-value
(95% CI)
Bleeding before coronary
angiography (Table 3)
Bleeding before coronary
Number of antithrombotic
drugs
HR 1.28 (1.09 –
0.003
1.51)
Bivalirudin+GPI vs.
UFH+GPI
HR 0.98 (0.74 –
1.29)
0.87
Bivalirudin alone vs.
UFH+GPI
Bleeding before coronary
HR 0.43 (0.30 –
0.61)
HR 1.94 (1.26 –
<0.001
angiography (Table 4)
Death within 1 year (Table 6)
angiography
Death within 1 year (Table 6;
Alternative Model)
Bleeding before coronary
angiography
0.003
2.98)
HR 1.93 (1.25 –
0.004
2.97)
Sensitivity analyses for multivariable adjusted Cox proportional hazards models using complete
case data. Table references within parentheses refer to the tables in which the primary models
using multiple imputation were presented. The complete case models were adjusted for the same
covariates as the primary models.
CI, confidence interval; GPI, glycoprotein inhibitor; HR, hazard ratio; UFH, unfractionated
heparin
Supplemental Table 3. Sensitivity analysis: Poisson regression model
Model
Relative Risk
(95% Confidence Interval)
p Value
Unadjusted
2.31 (1.52 – 3.51)
<0.001
Adjusted
1.91 (1.24 - 2.94)
0.003
Adjusted – alternative*
1.90 (1.23 - 2.93)
0.004
Sensitivity analysis for the primary Cox proportional hazards model presented in Table 6. A
binary indicator variable for whether or not the patient bled before coronary angiography was
included in a Poisson regression model along with the following covariates: Age, sex, insulintreated diabetes, current smoking, previous percutaneous coronary intervention, previous
coronary artery bypass graft surgery, weight, renal failure, and biomarker positivity. The
dependent variable was death within one year, using the Poisson distribution and the logarithm of
survival time.
*Included, in addition to the above covariates, treatment assignment (ie, bivalirudin alone,
bivalirudin+glycoprotein IIb/IIIa inhibitor, or heparin+glycoprotein IIb/IIIa inhibitor).
Supplemental Figure 1. Kaplan-Meier Failure Curves – Time to Bleeding Before
Angiography Stratified by Treatment Assignment
Time (hours) from enrollment in the trial to bleeding (event) or coronary angiography
(censored). GPI = glycoprotein IIb/IIIa inhibitor; UFH = unfractionated heparin.
Supplemental Figure 2. Time to Bleeding and Myocardial Infarction Before Coronary
Angiography Stratified by Objective Signs of Ischemia
(A) Time from enrollment in the trial to bleeding (event) or coronary angiography (censored).
(B) Time from enrollment in the trial to major bleeding (event) or coronary angiography
(censored). (C) Time from enrollment in the trial to myocardial infarction (MI) (event) or
coronary angiography (censored).
Supplemental Figure 2A
Supplemental Figure 2B
Supplemental Figure 2C
Supplemental Figure 3. Kaplan-Meier failure Curves – Time to Bleeding and Myocardial
Infarction Before Angiography Stratified by Thrombolysis In Myocardial Infarction Risk
Score
(A) Time from enrollment in the trial to bleeding (event) or coronary angiography (censored).
(B) Time from enrollment in the trial to myocardial infarction (event) or coronary angiography
(censored). MI = myocardial infarction; TIMI = thrombolysis in myocardial infarction.
Supplemental Figure 3A
Supplemental Figure 3B
Supplementary Figure 4. Kaplan-Meier Failure Curves – Time to Death for Patients Who
Bled Before Angiography
Landmark analysis: Time from coronary angiography to death for patients stratified according to
whether or not they had a bleeding event prior to undergoing angiography.