Online Supplementary Table 1. Characteristics of included randomized controlled trials. BMS: Bare Metal Stent; CAD:
Coronary Artery Disease; DAPT: Dual Antiplatelet Therapy; NSTEMI: Non-ST segment Elevation Myocardial Infarction;
STEMI: ST segment Elevation Myocardial Infarction; UA: Unstable Angina.
Study
RAVEL
Year
2002
Patients
238
Women
58 (24)
Stents used
Cypher, BMS
Key inclusion
Key exclusion
Minimum duration
criteria
criteria
of DAPT
Stable CAD or
NSTEMI or
2 Months
UA, single de-
STEMI
novo lesion
SIRIUS
2003
1058
305
Cypher, BMS
(29%)
Stable CAD or
NSTEMI or
UA, single de-
STEMI
3 Months
novo lesion
E-SIRIUS
2003
352
103
Cypher, BMS
(29%)
Stable CAD or
NSTEMI or
UA, single de-
STEMI
2 Months
novo lesion
C-SIRIUS
2004
100
31 (31%)
Cypher, BMS
1
Stable CAD or
NSTEMI or
UA, single de-
STEMI
3 Months
novo lesion
TAXUS I
TAXUS II SR
2003
2003
61
267
7 (11%)
67 (25%)
Taxus, BMS
Taxus, BMS
Stable CAD or
NSTEMI or
UA, single lesion
STEMI
Stable CAD or
NSTEMI or
UA, single de-
STEMI
6 Months
6 Months
novo lesion
TAXUS IV
2004
1314
367
Taxus, BMS
(28%)
Stable CAD or
NSTEMI or
UA, single de-
STEMI
6 Months
novo lesion
TAXUS V
2005
1156
353
Taxus, BMS
(31%)
Stable CAD or
NSTEMI or
UA, single de-
STEMI
6 Months
novo lesion
SIRTAX
2005
1012
231
Cypher, Taxus
(23%)
Stable CAD or
None
12 Months
NSTEMI or
3 Months
UA, single denovo lesion
ENDEAVOR II
2006
1197
283
Endeavor, BMS
2
Stable CAD or
(24%)
UA, single de-
STEMI
novo lesion
ENDEAVOR III
2006
436
133
Endeavor, Cypher
(31%)
Stable CAD or
NSTEMI or
UA, single de-
STEMI
3 Months
novo lesion
ENDEAVOR IV
2010
1548
500
Endeavor, Taxus
(32%)
Stable CAD or
NSTEMI or
UA, single de-
STEMI
6 Months
novo lesion
PROTECT
2012
8709
2061
Endeavor, Cypher
(24%)
Stable CAD or
None
12 Months
None
6 Months
STEMI
12 Months
NSTEMI or
6 Months
UA, single denovo lesion
RESOLUTE AC
2010
2292
529
Resolute, Xience
(23%)
TWENTE
2012
1391
382
NSTEMI or STEMI
Resolute, Xience
(27%)
SPIRIT II
2006
300
80 (27%)
Stable CAD, UA,
Stable CAD, UA
or NSTEMI
Xience, Taxus
3
Stable CAD, UA
or 2 de-novo
STEMI
lesions
SPIRIT III
2008
1002
314 (31)
Xience, Taxus
Stable CAD, UA
NSTEMI or
or 2 de-novo
STEMI
6 Months
lesions
SPIRIT IV
2010
3687
1189 (32)
Xience, Taxus
Stable CAD, UA
NSTEMI or
or 3 de-novo
STEMI
12 Months
lesions
COMPARE I
2010
1800
526
Xience, Taxus
(29%)
BASKET-PROVE
2010
2314
565
Stable CAD, UA,
None
12 Months
None
12 Months
STEMI
6 Months
NSTEMI or STEMI
Xience, Cypher, BMS
(24%)
Stable CAD, UA
or acute MI, target
vessel diameter ≥
3.0 mm
EXCELLENT
2011
1443
512
Xience, Promus, Cypher
(35%)
Stable CAD, UA,
NSTEMI
4
RESET
2012
3197
742
Xience, Cypher
(23%)
PRODIGY
LEADERS
2012
2008
2013
1707
2013
2707
473
Xience, Promus,
Stable CAD, UA,
(23%)
Endeavor, Taxus, BMS
NSTEMI or STEMI
430
Biomatrix, Cypher
Stable CAD, UA,
293
2009
2603
623
3 Months
None
6 Months
None
12 Months
None
12 Months
None
6 Months
NSTEMI or STEMI
Nobori, Xience, Promus
(26%)
ISAR-TEST 4
None
NSTEMI or STEMI
(25%)
COMPARE II
Stable CAD, UA,
Stable CAD, UA,
NSTEMI or STEMI
Yukon, Xience, Cypher
(24%)
Stable CAD, UA,
NSTEMI or STEMI
5
Online Supplementary Table 2. Clinical endpoint definitions used across randomized controlled trials. ARC: Academic
Research Consortium; CK: Creatine-Kinase; ECG = Electrocardiogram; MI: Myocardial Infarction; URL: Upper Reference
Limit.
Trial name
RAVEL
Myocardial infarction
Target lesion revascularization
Stent thrombosis
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
ARC criteria
with elevated cardiac enzymes or, in the absence
stenosis of the luminal diameter
of Q waves, increase in the CK level ≥2*ULN and
anywhere within the stent or within the 5-
increased level of CK-MB
mm borders proximal or distal to the
stent.
SIRIUS
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
with elevated cardiac enzymes or, in the absence
stenosis of the luminal diameter
of Q waves, increase in the CK level ≥2*ULN and
anywhere within the stent or within the 5-
increased level of CK-MB
mm borders proximal or distal to the
ARC criteria
stent.
E-SIRIUS
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
with elevated cardiac enzymes or, in the absence
stenosis of the luminal diameter
6
ARC criteria
of Q waves, increase in the CK level ≥2*ULN and
anywhere within the stent or within the 5-
increased level of CK-MB
mm borders proximal or distal to the
stent.
C-SIRIUS
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
with elevated cardiac enzymes or, in the absence
stenosis of the luminal diameter
of Q waves, increase in the CK level ≥2*ULN and
anywhere within the stent or within the 5-
increased level of CK-MB
mm borders proximal or distal to the
ARC criteria
stent.
TAXUS I
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
with CK and CK-MB levels elevated above
stenosis of the luminal diameter
normal
anywhere within the stent or within the 5-
ARC criteria
mm borders proximal or distal to the
stent.
TAXUS II SR
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
or, in the absence of Q waves, increase in the CK
stenosis of the luminal diameter
level ≥2*ULN and increased level of CK-MB
anywhere within the stent or within the 5-
7
ARC criteria
mm borders proximal or distal to the
stent.
TAXUS IV
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
or, in the absence of Q waves, increase in the CK
stenosis of the luminal diameter
level ≥2*ULN and increased level of CK-MB
anywhere within the stent or within the 5-
ARC criteria
mm borders proximal or distal to the
stent.
TAXUS V
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
or, in the absence of Q waves, increase in the CK
stenosis of the luminal diameter
level ≥2*ULN and increased level of CK-MB
anywhere within the stent or within the 5-
ARC criteria
mm borders proximal or distal to the
stent
SIRTAX
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
or, in the absence of Q waves, increase in the CK
stenosis of the luminal diameter
level ≥2*ULN and increased level of CK-MB or
anywhere within the stent or within the 5-
troponin I
mm borders proximal or distal to the
8
ARC criteria
stent
ENDEAVOR II
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
or, in the absence of Q waves, increase in the CK
stenosis of the luminal diameter
level ≥2*ULN and increased level of CK-MB
anywhere within the stent or within the 5-
ARC criteria
mm borders proximal or distal to the
stent
ENDEAVOR III
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
with elevated cardiac enzymes or, in the absence
stenosis of the luminal diameter
of Q waves, increase in the CK level ≥2*ULN and
anywhere within the stent or within the 5-
increased level of CK-MB
mm borders proximal or distal to the
ARC criteria
stent
ENDEAVOR IV
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
with elevated cardiac enzymes or, in the absence
stenosis of the luminal diameter
of Q waves, increase in the CK level ≥2*ULN and
anywhere within the stent or within the 5-
increased level of CK-MB
mm borders proximal or distal to the
stent
9
ARC criteria
ARC criteria
PROTECT
II Universal Definition (Thygesen K et al.
Revascularization for ischemia for a
Circulation 2007): Periprocedural MI: cardiac
stenosis of the luminal diameter
biomarkers increase ≥3*ULN Spontaneous:
anywhere within the stent or within the 5-
Typical rise and fall of cardiac biomarkers
mm borders proximal or distal to the
(preferably troponin) with at least 1 value >URL
stent
ARC criteria
and at least 1 of the following: symptoms, ST-T
changes at ECG, pathological Q waves, or
imaging evidence of ischemia
RESOLUTE AC
Extended historical definition (Vranckx et al.
Revascularization for ischemia for a
Eurointervention 2010). In summary:
stenosis of the luminal diameter
development of Q waves in ≥2 contiguous leads
anywhere within the stent or within the 5-
and elevated cardiac enzymes or, in the absence
mm borders proximal or distal to the
of Q waves, increase in the CK level ≥2*ULN and
stent
increased level of CK-MB or troponin. In patients
with acute MI at baseline: if cardiac biomarkers
10
ARC criteria
still raising new chest pain of ischemia equivalent
and rise in cardiac biomarkers >50% previous
level; if cardiac biomarkers have returned to
normal, CK level ≥2*ULN.
TWENTE
Extended historical definition (Vranckx et al.
Revascularization for ischemia for a
Eurointervention 2010). In summary:
stenosis of the luminal diameter
development of Q waves in ≥2 contiguous leads
anywhere within the stent or within the 5-
and elevated cardiac enzymes or, in the absence
mm borders proximal or distal to the
of Q waves, increase in the CK level ≥2*ULN and
stent
ARC criteria
increased level of CK-MB or troponin. In patients
with acute MI at baseline: if cardiac biomarkers
still raising new chest pain of ischemia equivalent
and rise in cardiac biomarkers >50% previous
level; if cardiac biomarkers have returned to
normal, CK level ≥2*ULN.
SPIRIT II
Development of Q waves in ≥2 contiguous leads
11
Revascularization for ischemia for a
ARC criteria
or, in the absence of Q waves, a typical rise and
stenosis of the luminal diameter
fall of CK-MB (if non-procedural/spontaneous MI,
anywhere within the stent or within the 5-
CK-MB >2 times upper limit of normal; if post
mm borders proximal or distal to the
PCI, CK-MB >3 times upper limit of normal; if
stent
post CABG, CK-MB >5 times upper limit of
normal)
SPIRIT III
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
with elevated cardiac enzymes or, in the absence
stenosis of the luminal diameter
of Q waves, increase in the CK level ≥2*ULN and
anywhere within the stent or within the 5-
increased level of CK-MB
mm borders proximal or distal to the
ARC criteria
stent
SPIRIT IV
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
with elevated cardiac enzymes or, in the absence
stenosis of the luminal diameter
of Q waves, increase in the CK level ≥2*ULN and
anywhere within the stent or within the 5-
increased level of CK-MB
mm borders proximal or distal to the
stent
12
ARC criteria
COMPARE
Periprocedural MI (in patients without acute MI at
Revascularization for ischemia for a
baseline): any elevation in concentrations of CK
stenosis of the luminal diameter
≥2*ULN and increase in CK-MB or troponin.
anywhere within the stent or within the 5-
Spontaneous MI: typical rise and fall of troponin
mm borders proximal or distal to the
or CK-MB with at least one of the following:
stent
ARC criteria
ischemic symptoms, development of pathological
Q waves, ischemic ECG changes, or pathological
findings of an acute MI
BASKET-PROVE
Typical rise and fall of cardiac biomarkers
Target vessel Revascularization was
(preferably troponin) with at least 1 value >URL
used
ARC criteria
and at least 1 of the following: symptoms, ST-T
changes at ECG, pathological Q waves, or recent
angioplasty.
EXCELLENT
Academic Research Consortium criteria (Cutlip
Revascularization for ischemia for a
DE et al. Circulation 2007) In summary:
stenosis of the luminal diameter
Periprocedural MI: troponin >3*URL or CK-
anywhere within the stent or within the 5-
13
ARC criteria
MB>3*URL if baseline cardiac biomarkers <URL.
mm borders proximal or distal to the
Stable or decreasing values on 2 samples
stent
followed by 20% increase if baseline cardiac
biomarkers >URL.
Spontaneous MI: troponin >URL or CK-MB >URL
RESET
Periprocedural MI: CK-MB ≥3*ULN or CK
Revascularization for ischemia for a
≥3*ULN in the absence of CKMB measurement.
stenosis of the luminal diameter
Spontaneous MI: Academic Research
anywhere within the stent or within the 5-
Consortium criteria (Cutlip DE et al. Circulation
mm borders proximal or distal to the
2007), troponin >URL or CK-MB >URL
stent
ARC criteria
ARC criteria
PRODIGY
II Universal Definition (Thygesen K et al.
Target vessel Revascularization was
Circulation 2007): Periprocedural MI: cardiac
used
biomarkers increase ≥3*ULN Spontaneous:
Typical rise and fall of cardiac biomarkers
(preferably troponin) with at least 1 value >URL
14
ARC criteria
and at least 1 of the following: symptoms, ST-T
changes at ECG, pathological Q waves, or
imaging evidence of ischemia
LEADERS
Development of Q waves in ≥2 contiguous leads
Revascularization for ischemia for a
or, in the absence of Q waves, increase in the CK
stenosis of the luminal diameter
level ≥2*ULN and increased level of CK-MB or
anywhere within the stent or within the 5-
troponin I
mm borders proximal or distal to the
ARC criteria
stent
COMPARE-2
Periprocedural MI (in patients without acute MI at
Revascularization for ischemia for a
baseline):any elevation in concentrations of CK
stenosis of the luminal diameter
≥2*ULN and increase in CK-MB or troponin.
anywhere within the stent or within the 5-
Spontaneous MI: typical rise and fall of troponin
mm borders proximal or distal to the
or CK-MB with at least one of the following:
stent
ischemic symptoms, development of pathological
Q waves, ischemic ECG changes, or pathological
findings of an acute MI
15
ARC criteria
ISAR-TEST 4
Periprocedural MI: CK-MB (or CK) ≥3*ULN and
Revascularization for ischemia for a
at least 50% over the most recent pre-PCI levels,
stenosis of the luminal diameter
or the development of new ECG changes
anywhere within the stent or within the 5-
consistent with MI and CK-MB (CK) elevation
mm borders proximal or distal to the
>ULN at 2 measurements for patients with stable
stent
angina pectoris or NSTE-ACS and falling or
normal CK-MB (CK) levels. Recurrent chest pain
lasting .30 min with either new ECG changes
consistent with second MI or next CK-MB (CK)
level at least 8–12 h after PCI elevated at least
50% above the previous level was considered
procedure-related MI for patients presenting with
elevated CK-MB (CK) level prior to PCI.
Spontaneous MI: any CK-MB increase with or
without the development of Q-waves on ECG.
16
ARC criteria
Online Supplementary Table 3. Adjusted 3-year clinical outcomes between early- and new-generation drug-eluting
stents in women with or without CrCl < 45 ml / min. HR: Hazard Ratio; CI: Confidence Interval.
No CKD (CrCl ≥ 45)
Early-Gen
New-Gen
DES
DES
Death
49 (2.7)
49 (2.6)
Cardiac Death
33 (1.8)
Myocardial Infarction
CKD (CrCl < 45)
Early-Gen New-Gen
Adjusted HR [95% CI]
Adjusted HR [95% CI]
Pint
32 (11.4)
0.68 [0.41,1.11]
0.43
24 (7.5)
17 (6.1)
0.55 [0.28,1.08]
0.34
0.83 [0.59,1.16]
29 (9.0)
22 (7.8)
0.59 [0.32,1.09]
0.35
92 (4.9)
1.35 [0.96,1.90]
16 (5.0)
18 (6.4)
1.10 [0.55,2.20]
0.73
20 (1.1)
16 (0.9)
0.67 [0.34,1.33]
7 (2.2)
5 (1.8)
0.50 [0.15,1.67]
0.89
Death or MI
129 (7.2)
124 (6.6)
0.87 [0.66,1.15]
61 (18.9)
47 (16.7)
0.66 [0.43,0.99]
0.32
Cardiac Death, MI or ST
114 (6.4)
113 (6.0)
0.87 [0.65,1.16]
46 (14.3)
36 (12.8)
0.63 [0.39,1.02]
0.31
DES
DES
0.88 [0.57,1.37]
40 (12.4)
31 (1.7)
0.78 [0.46,1.33]
91 (5.1)
86 (4.6)
TLR
93 (5.2)
Definite or Probable ST
17
Online Supplementary Figure 1.
18
Online Supplemental Figure Legend:
Online Supplementary Figure 1. Adverse events at 3 years according to baseline renal function. CrCl: Creatinine Clearance; MACE:
Major Adverse Cardiac Events; MI: Myocardial Infarction; TLR: Target Lesion Revascularization; ST: Stent Thrombosis.
19