ONLINE-ONLY DATA SUPPLEMENT:
TABLE_I: KEY ELEMENTS OF THE BLEEDING CLASSIFICATIONS USED IN THIS ANALYSIS
BARC BLEEDING CLASSIFICATION (7)
TYPE 2
Any overt, actionable sign of hemorrhage (eg, more bleeding than
would be expected for a clinical circumstance, including bleeding
found by imaging alone) that does not fit the criteria for type 3, 4, or 5
but does meet at least one of the following criteria:
(1) requiring nonsurgical, medical intervention by a healthcare
professional,
(2) leading to hospitalization or increased level of care, or
(3) prompting evaluation
TYPE 3
TYPE 3A

Overt bleeding plus hemoglobin drop of 3 to <5 g/dL* (provided
hemoglobin drop is related to bleed)

Any transfusion with overt bleeding
TYPE 3B

Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided
hemoglobin drop is related to bleed)

Cardiac tamponade

Bleeding requiring surgical intervention for control (excluding
dental/nasal/skin/hemorrhoid)

Bleeding requiring intravenous vasoactive agents
TYPE 3C

Intracranial hemorrhage (does not include microbleeds or
hemorrhagic
transformation, does include intraspinal)

Subcategories confirmed by autopsy or imaging or lumbar
puncture

TYPE 5
Intraocular bleed compromising vision
TYPE 5A

Probable fatal bleeding; no autopsy or imaging confirmation but
clinically suspicious
TYPE 5B

Definite fatal bleeding; overt bleeding or autopsy or imaging
confirmation
TIMI BLEEDING CLASSIFICATION (13)*
MAJOR

Intracranial hemorrhage or a ≥5 g/dl decrease in the
hemoglobin concentration or a ≥15% absolute decrease in the
hematocrit
MINOR

Observed blood loss: ≥3 g/dl but < 5 g/dl decrease in the
hemoglobin concentration or ≥10% but < 15% decrease in the
hematocrit

No observed blood loss: ≥4 g/dl decrease in the hemoglobin
concentration or ≥12% decrease in the hematocrit
REQUIRING

MEDICAL
ATTENTION
Any overt sign of hemorrhage that meets one of the following
criteria and does not meet criteria for a major or minor bleeding
event, as defined above

Requiring intervention (medical practitioner-guided medical or
surgical treatment to stop or treat bleeding, including
temporarily or permanently discontinuing or changing the dose
of a medication or study drug)

Leading to or prolonging hospitalization

Prompting evaluation (leading to an unscheduled visit to a
healthcare professional and diagnostic testing, either laboratory
or imaging)
GUSTO BLEEDING CLASSIFICATION (14)
SEVERE OR

Intracranial hemorrhage
LIFE-

A bleeding event that causes hemodynamic compromise and
requires intervention
THREATENING
MODERATE

A bleeding event that requires blood transfusion but does not
result in hemodynamic compromise
MILD

Bleeding that does not meet above criteria
*All BARC and TIMI definitions take into account blood transfusions, so that
hemoglobin and hematocrit values are adjusted by 1 g/dl or 3%, respectively, for
each unit of blood transfused. Therefore, the true change in hemoglobin or
hematocrit if there has been an intervening transfusion between two blood
measurements is calculated as follows: Δ Hemoglobin (Hgb) = [baseline Hgb - posttransfusion Hgb] + [number of transfused units]; ΔHematocrit (Hct) = [baseline Hct post-transfusion Hct] + [number of transfused units x 3].
BARC: Bleeding Academic Research Consortium, GUSTO: Global Strategies for
Opening Occluded Coronary Arteries; TIMI: Thrombolysis In Myocardial Infarction.
TABLE_II: LINKING BARC CLASS II, III AND V TO GUSTO, TIMI BLEEDING SCALES


No bleeding reported/
BARC
No evidence of bleeding
captured
Type 0
Bleeding not qualifying as
BARC
Bleeding that is not actionable and does not cause the patient to seek unscheduled
any TIMI BLEEDING requiring
Type 1
performance of studies, hospitalization, or treatment by a healthcare professional.
TIMI BLEEDING requiring
BARC
Any overt, actionable sign of hemorrhage§ that does not fit the criteria for type 3, 4, or
medical attention and GUSTO
TYPE 2
5 but does meet at least one of the following criteria:
medical attention, not
qualifying as GUSTO MILD

MILD

TIMI MINOR and GUSTO MILD
BARC

requiring nonsurgical, medical intervention by a healthcare professional,

leading to hospitalization or increased level of care, or

prompting evaluation

Overt bleeding plus hemoglobin drop of 3 to <5 g/dL* (provided hemoglobin
TYPE 3A
drop is related to bleed)

Any transfusion with overt bleeding

TIMI MAJOR;

GUSTO SEVERE;

Reported
BARC
TYPE 3B
Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided hemoglobin drop is
related to bleed)
Pericardial

Cardiac tamponade
Bleeding and GUSTO severe

Bleeding requiring surgical intervention for control (excluding
(excluding
CABG
related
dental/nasal/skin/hemorrhoid)
bleeding)


INTRACRANIAL BLEEDING
excluding ischemic stroke
BARC

Bleeding requiring intravenous vasoactive agents

Intracranial hemorrhage (does not include micro-bleeds or hemorrhagic trans-
TYPE 3C
formation, does include intra-spinal)
with hemorrhagic

Subcategories confirmed by autopsy or imaging or lumbar puncture
transformation

Intraocular bleed compromising vision
§ e.g., more bleeding than would be expected for a clinical circumstance, including bleeding
TABLE_III: BASELINE CHARACTERISTICS IN THE 2003 PATIENTS INCLUDED.
Characteristic
Age (years) - median (IQR)
All patients
69.4 (60.2,76.4)
Short DAT
Long DAT
(N=1005)
(N=998)
69.5
69.4
(59.8,76.9)
(60.8,75.9)
P value
0.819
Females - n (%)
473 (23.6)
243 (24.2)
230 (23)
0.551
BMI (kg/m2) - median (IQR)
26.6 (24.5,29.4)
26.6
26.6
0.223
(24.2,29.3)
(24.7,29.4)
Diabetes - n (%)
488 (24.4) a
237 (23.6)
251 (25.1)
0.440
PAD - n (%)
252 (12.6)
132 (13.1)
120 (12)
0.454
Hypertension - n (%)
1438 (71.8) b
712 (71.1)
726 (72.7)
0.158
Non-smokers - n (%)
1040 (51.9) c
527 (52.9)
513 (51.7)
0.210
Dyslipidemia - n (%)
1091 (54.5) d
536 (53.4)
555 (55.6)
0.369
Family history of premature
556 (27.8) e
266 (27.6)
290 (29.9)
0.134
Prior MI - n (%)
536 (26.8) f
260 (26)
276 (27.7)
0.059
Prior coronary
502 (25.1) g
243 (24.3)
259 (26)
0.183
CAD - n (%)
revascularization - n (%)
N° of diseased coronaries - n (%)
1- vessel
601 (30)
305 (30.4)
296 (29.6)
2- vessels
714 (35.7)
358 (35.6)
356 (35.7)
3- vessels
688 (34.3)
342 (34)
346 (34.7)
LVEF (%)- median (IQR)
50.5 (43,60)
50 (43,60)
54.5 (44.5,60)
0.207
Creatinine Clearance (ml) -
74.5 (56.2,96.2)
74.6
74 (56,99.2)
0.832
746 (74.7)
0.806
median (IQR)
ACS presentation (ST- or
0.933
(56.9,94.7)
1502 (75)
756 (75.2)
NSTE) - n (%)
Continuous variables are reported as median (25 th, 75th percentiles), categorical
variables as proportions. Percentage may differ according to number of missing
6
values: a 1 missing value, b 3 missing values, c 13 missing values, d 1 missing value, e
70 missing values, f 5 missing values, g 6 missing values
ACS denotes acute coronary syndrome, either ST-segment elevation or non-ST
segment elevation; BMI: body mass index; DAT: dual anti-aggregation therapy; CAD:
coronary artery disease; IQR: interquartile range; LVEF: left ventricular ejection
fraction; MI: myocardial infarction; PAD: peripheral artery disease.
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TABLE IV. UNADJUSTED HAZARD RATIOS FOR DEATH AT 2 YEARS FOR DIFFERENT BLEEDING TYPES AND TIMING (EARLY [0-180DAYS] AND
DELAYED[>180DAYS]).
Predictor
N
N
Hazard Ratio (95%CI)
P value
N
N events Hazard Ratio (95%CI)
P value
events
0-180days
>180days
BARC
Type 2
37
3
0.965 (0.308-3.025)
0.952
39
0
0 (0-Inf)
0.992
Type 3
31
10
6.264 (3.472-11.301)
<.0001
36
13
4.417 (2.390-8.161)
<.0001
Type 3A
17
5
4.069 (1.67-9.915)
0.002
21
4
2.342 (0.868-6.320)
0.093
Type 3B
9
3
6.939 (2.571-18.73)
0.0001
5
2
2.686 (0.376-19.19)
0.325
Type 3C
5
2
10.621 (3.384-33.33)
<.0001
9
7
9.618 (4.251-21.76)
<.0001
Type 2,3 (or 5)
68
13
3.189 (1.871-5.435)
<.0001
75
13
1.987 (1.075-3.672)
0.029
MAJOR
13
7
9.408 (4.404-20.10)
<.0001
11
7
9.697 (4.540-20.71)
<.0001
MINOR
10
2
2.642 (0.655-10.657)
0.172
16
3
2.361 (0.753-7.398)
0.141
MAJOR or
23
9
6.313 (3.218-12.39)
<.0001
27
10
5.328 (2.806-10.12)
<.0001
TIMI
8
MINOR
GUSTO
Severe
15
4
8.040 (3.764-17.17)
<.0001
12
2
8.729 (4.088-18.64)
<.0001
Moderate
15
7
3.673 (1.361-9.909)
0.010
19
7
1.291 (0.320-5.208)
0.72
Moderate or
30
11
5.936 (3.213-10.965)
<.0001
31
9
4.072 (2.076-7.987)
<.0001
Severe
BARC: Bleeding Academic Research Consortium, GUSTO: Global Strategies for Opening Occluded Coronary Arteries; TIMI:
Thrombolysis In Myocardial Infarction.
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TABLE V. UNADJUSTED* HAZARD RATIOS FOR DEATH AT 2 YEARS FOR DIFFERENT BLEEDING TYPE AND DURATION OF DUAL ANTI-AGGREGATION
THERAPY.
Predictor
N events
Hazard Ratio (95%CI)
P
N
value
events
Short DAPT
Hazard Ratio (95%CI)
P value
Long DAPT
BARC
Type 2
1
0.798 (0.111-5.751)
0.823
2
1.21 (0.294-4.98)
0.792
Type 3
11
14.722 (7.754-27.953)
<.0001
12
11.48 (6.106-21.57)
<.0001
Type 3A
5
11.081 (4.45-27.588)
<.0001
4
5.674 (2.048-15.722)
<.0001
Type 3B
2
10.770 (2.63-44.104)
<.0001
3
12.445 (3.884-39.877)
<.0001
Type 3C
4
35.685 (12.946-
<.0001
5
55.309 (21.682-
<.0001
98.366)
Type 2, 3 (or 5)
141.088)
12
5.992 (3.233-11.11)
<.0001
14
5.201 (2.869-9.429)
<.0001
5
18.427 (7.401-45.882)
<.0001
9
36.958 (18.056-
<.0001
TIMI
MAJOR
10
11
75.647)
MINOR
4
13.442 (4.876-37.057)
<.0001
1
2.085 (0.288-15.104)
0.467
MAJOR or MINOR
9
15.597 (7.765-31.33)
<.0001
10
13.45 (6.833-26.47)
<.0001
Severe
4
13.447 (5.401-33.48)
<.0001
2
38.277 (18.754-78.13)
<.0001
Moderate
5
8.166 (2.972-22.43)
<.0001
9
3.385 (0.822-13.94)
0.091
Moderate or Severe
9
10.44 (5.193-21)
<.0001
11
13.37 (6.942-25.74)
<.0001
GUSTO
BARC: Bleeding Academic Research Consortium, GUSTO: Global Strategies for Opening Occluded Coronary Arteries; TIMI:
Thrombolysis In Myocardial Infarction.
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TABLE VI. UNIVARIATE HR FOR 2-YEAR DEATH OF COVARIATES INCLUDED IN THE
MULTIVARIABLE MODEL.
Hazard Ratio
P value
(95%CI)
Age (1 year)
1.087 (1.068-1.106)
<.0001
Females
1.592 (1.147-2.209)
0.005
BMI
0.958 (0.920-0.998)
0.041
ACS presentation
2.105 (1.354-3.271)
0.001
Diabetes
1.573 (1.135-2.179)
0.007
PAD
2.769 (1.964-3.904)
<.0001
Creatinine Clearance (l/min)
0.971 (0.965-0.977)
<.0001
LVEF
0.944 (0.931-0.957)
<.0001
N° diseased vessel(s)
1.327 (1.090-1.615)
0.005
N° of risk factors
0.966 (0.859-1.087)
0.563
N° of B2/C type lesion
1.24 (1.03-1.493)
0.023
- ZES
0.752 (0.484-1.167)
0.203
- PES
1.093 (0.733-1.632)
0.662
- EES
0.685 (0.436-1.075)
0.1
Long vs. short DAPT
0.872 (0.641-1.186)
0.382
R1 (stent type; BMS refer.)
ACS denotes acute coronary syndrome, either ST-segment elevation or non-ST
segment elevation; BMI: body mass index; BMS: or thin-strut bare metal stent; DAT:
dual anti-aggregation therapy; DAPT: dual antiplatelet therapy; EES: everolimus-
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13
eluting stent; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PAD:
peripheral artery disease; PES: paclitaxel-eluting stent; ZES: zotarolimus-eluting
Endeavor Sprint®stent.
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