Supplemental Materials

Supplemental Methods

Definitions of clinical events

All the endpoints evaluated in this study were pre-specified. Endpoints assessed in the CREDO-Kyoto registry cohort-2 included death (all-cause/cardiac/sudden/non-cardiac), myocardial infarction, stent thrombosis, stroke, hospitalization for heart failure, bleeding, target-lesion revascularization, and any coronary revascularization. Death was regarded as cardiac in origin unless obvious non-cardiac causes could be identified. Any death during the index hospitalization was regarded as cardiac death. Sudden death was defined as unexplained death in previously stable patients. Myocardial infarction was defined according to the definition in the Arterial Revascularization Therapy Study.1 Within 1 week of the index procedure, only Q-wave myocardial infarction was adjudicated as myocardial infarction. Stent thrombosis was defined according to the Academic Research Consortium definition.2 Stroke during follow-up was defined as ischemic or hemorrhagic stroke requiring hospitalization with symptoms lasting > 24 hour. Hospitalizaion for heart failure was defined as hospitalization due to worsening heart failure requiring intravenous drug therapy. Bleeding was defined according to the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries (GUSTO) classification.3 GUSTO moderate or severe bleeding was adjudicated as a bleeding event. Procedure-related bleeding was defined as that occurred during hospitalization for percutaneous interventional procedures or surgical procedures. Target-lesion revascularization was defined as either percutaneous coronary intervention or coronary artery bypass grafting due to restenosis or thrombosis of the target lesion that included the proximal and distal edge segments as well as the ostium of the side branches.

References.

1.  Serruys PW, Ong AT, van Herwerden LA, Sousa JE, Jatene A, Bonnier JJ, et al. Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: The final analysis of the arterial revascularization therapies study (ARTS) randomized trial. J Am Coll Cardiol. 2005;46:575-581.

2.  Mauri L, Hsieh WH, Massaro JM, Ho KK, D'Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med. 2007;356:1020-1029.

3.  The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329:673-682.

Supplemental Table 1. Baseline characteristics in AMI and Non-AMI Patients.

AMI / Non-AMI / P value
(N=2561) / (N=2344)
(A) Clinical characteristics
Age (years) / 66.5±12.2 / 68.4±10.7 / <0.0001
Age >= 75 years / 719 (28%) / 736 (31%) / 0.01
Male / 1919 (75%) / 1692 (72%) / 0.03
BMI / 23.8±3.5 / 23.8±3.4 / 0.5
BMI < 25.0 / 1777 (69%) / 1566 (67%) / 0.053
Hypertension / 2016 (79%) / 1982 (85%) / <0.0001
Diabetes mellitus / 813 (32%) / 802 (34%) / 0.07
on insulin therapy / 93 (3.6%) / 125 (5.3%) / 0.004
Current smoking / 1147 (45%) / 680 (29%) / <0.0001
Heart failure / 677 (26%) / 232 (9.9%) / <0.0001
Shock at presentation / 342 (13%) / 1 (0.04%) / <0.0001
Multivessel disease / 1057 (41%) / 1073 (46%) / 0.002
Mitral regurgitation grade 3/4 / 62 (2.4%) / 134 (5.7%) / <0.0001
Ejection fraction (%) / 54.1±12.3 / 62.9±11.3 / <0.0001
Prior myocardial infarction / 60 (2.3%) / 276 (12%) / <0.0001
Prior Stroke / 210 (8.2%) / 232 (9.9%) / 0.04
Peripheral vascular disease / 68 (2.7%) / 289 (12%) / <0.0001
eGFR < 30, not on dialysis / 85 (3.3%) / 87 (3.7%) / 0.46
Dialysis / 23 (0.9%) / 77 (3.3%) / <0.0001
Atrial Fibrillation / 222 (8.7%) / 198 (8.5%) / 0.78
Anemia (Hb < 11 g/dl) / 216 (8.4%) / 268 (11%) / 0.0004
Platelet < 100*109/L / 31 (1.2%) / 23 (1.0%) / 0.44
COPD / 86 (3.4%) / 105 (4.5%) / 0.04
Liver cirrhosis / 69 (2.7%) / 68 (2.9%) / 0.66
Malignancy / 193 (7.5%) / 276 (12%) / <0.0001
(B) Procedural characteristics
Number of target lesions / 1.26±0.56 / 1.35±0.67 / <0.0001
Target of proximal LAD / 1312 (51%) / 1241 (53%) / 0.23
Target of unprotected LMCA / 57 (2.2%) / 55 (2.4%) / 0.78
Target of CTO / 64 (2.5%) / 245 (11%) / <0.0001
Target of bifurcation / 552 (22%) / 533 (23%) / 0.32
Side-branch stenting / 63 (2.5%) / 47 (2.0%) / 0.28
Total number of stents / 1.41±0.77 / 1.48±0.86 / 0.004
Total stent length (mm) / 28.5±17.2 / 29.5±20.0 / 0.06
Total stent length > 28mm / 817 (32%) / 802 (34%) / 0.09
Minimum stent size (mm) / 3.13±0.47 / 3.06±0.51 / <0.0001
Minimum stent size <3.0mm / 624 (24%) / 782 (33%) / <0.0001
IVUS use / 571 (22%) / 606 (26%) / 0.004
(C) Baseline medication
Medication at hospital discharge
Antiplatelet therapy
Thienopyridine / 2545 (99%) / 2305 (98%) / 0.0005
Ticlopidine / 2334 (92%) / 2144 (94%) / 0.03
Clopidogrel / 204 (8.0%) / 147 (6.4%) / 0.03
Aspirin / 2556 (99%) / 2329 (99%) / 0.01
Cilostazol / 753 (29%) / 326 (14%) / <0.0001
Other medications
Statins / 1398 (55%) / 1062 (45%) / <0.0001
Beta-blockers / 1098 (43%) / 508 (22%) / <0.0001
ACE-I / ARB / 1896 (74%) / 1168 (50%) / <0.0001
Nitrates / 709 (28%) / 968 (41%) / <0.0001
Calcium channel blockers / 502 (20%) / 1250 (53%) / <0.0001
Nicorandil / 809 (32%) / 451 (19%) / <0.0001
Warfarin / 235 (9.2%) / 143 (6.1%) / <0.0001
Proton pump inhibitors/ H2-blockers / 1735 (68%) / 1038 (44%) / <0.0001

Values are expressed as mean ± SD or number (%).

AMI=acute myocardial infarction, DAPT=dual antiplatelet therapy, SAPT=single antiplatelet therapy, BMI=body mass index, eGFR=estimated glomerular filtration rate, COPD=chronic obstructive pulmonary disease, LAD=left anterior descending coronary artery, LMCA=left main coronary artery, CTO=chronic total occlusion, IVUS=intravascular ultrasound, ACE-I=angiotensin converting enzyme inhibitors, and ARB=angiotensin II receptor blockers.

Supplemental Table 2. Baseline characteristics: DAPT versus SAPT at the 2-Month Landmark Point in AMI and Non-AMI Stratum

AMI Stratum / Non-AMI Stratum
SAPT / DAPT / P value / SAPT / DAPT / P value
(N=1257) / (N=1304) / (N=1318) / (N=1026)
(A) Clinical characteristics
Age (years) / 66.2±12.5 / 66.7±12.0 / 0.22 / 68.7±10.9 / 68.1±10.3 / 0.22
Age >= 75 years / 340 (27%) / 379 (29%) / 0.26 / 425 (32%) / 311 (30%) / 0.32
Male / 915 (73%) / 1004 (77%) / 0.01 / 920 (70%) / 772 (75%) / 0.003
BMI / 23.8±3.6 / 23.8±3.5 / 0.89 / 23.6±3.4 / 24.1±3.5 / 0.003
BMI < 25.0 / 855 (68%) / 922 (71%) / 0.14 / 884 (67%) / 682 (66%) / 0.76
Hypertension / 1010 (80%) / 1006 (77%) / 0.048 / 1114 (85%) / 868 (85%) / 0.96
Diabetes mellitus / 377 (30%) / 436 (33%) / 0.06 / 421 (32%) / 381 (37%) / 0.009
on insulin therapy / 36 (2.9%) / 57 (4.4%) / 0.04 / 61 (4.6%) / 64 (6.2%) / 0.09
Current smoking / 581 (46%) / 566 (43%) / 0.15 / 362 (27%) / 318 (31%) / 0.06
Heart failure / 333 (26%) / 344 (26%) / 0.95 / 117 (8.9%) / 115 (11%) / 0.06
Shock at presentation / 165 (13%) / 177 (14%) / 0.74 / 1 (0.08%) / 0 (0%) / 0.28
Multivessel disease / 512 (41%) / 545 (42%) / 0.59 / 564 (43%) / 509 (50%) / 0.001
Mitral regurgitation grade 3/4 / 30 (2.4%) / 32 (2.5%) / 0.91 / 83 (6.3%) / 51 (5.0%) / 0.17
Ejection fraction (%) / 54.9±12.2 / 53.2±12.4 / 0.001 / 63.5±11.2 / 62.1±11.5 / 0.01
Prior myocardial infarction / 29 (2.3%) / 31 (2.4%) / 0.91 / 147 (11%) / 129 (13%) / 0.29
Prior Stroke / 86 (6.8%) / 124 (9.5%) / 0.01 / 115 (8.7%) / 117 (11%) / 0.03
Peripheral vascular disease / 31 (2.5%) / 37 (2.8%) / 0.56 / 171 (13%) / 118 (12%) / 0.28
eGFR < 30, not on dialysis / 45 (3.6%) / 40 (3.1%) / 0.47 / 44 (3.3%) / 43 (4.2%) / 0.28
Dialysis / 10 (0.8%) / 13 (1.0%) / 0.59 / 48 (3.6%) / 29 (2.8%) / 0.27
Atrial Fibrillation / 105 (8.4%) / 117 (9.0%) / 0.58 / 110 (8.4%) / 88 (8.6%) / 0.84
Anemia (Hb < 11 g/dl) / 103 (8.2%) / 113 (8.7%) / 0.67 / 157 (12%) / 111 (11%) / 0.41
Platelet < 100*109/L / 21 (1.7%) / 10 (0.8%) / 0.03 / 17 (1.3%) / 6 (0.6%) / 0.08
COPD / 42 (3.3%) / 44 (3.4%) / 0.96 / 61 (4.6%) / 44 (4.3%) / 0.69
Liver cirrhosis / 33 (2.6%) / 36 (2.8%) / 0.83 / 46 (3.5%) / 22 (2.1%) / 0.051
Malignancy / 94 (7.5%) / 99 (7.6%) / 0.91 / 153 (12%) / 123 (12%) / 0.78
(B) Procedural characteristics
Number of target lesions / 1.26±0.58 / 1.25±0.55 / 0.48 / 1.33±0.64 / 1.38±0.71 / 0.04
Target of proximal LAD / 654 (52%) / 658 (50%) / 0.43 / 703 (53%) / 538 (52%) / 0.66
Target of unprotected LMCA / 14 (1.1%) / 43 (3.3%) / 0.0001 / 20 (1.5%) / 35 (3.4%) / 0.003
Target of CTO / 30 (2.4%) / 34 (2.6%) / 0.72 / 144 (11%) / 105 (10%) / 0.59
Target of bifurcation / 244 (19%) / 308 (24%) / 0.01 / 275 (21%) / 258 (25%) / 0.01
Side-branch stenting / 23 (1.8%) / 40 (3.1%) / 0.04 / 25 (1.9%) / 22 (2.1%) / 0.67
Total number of stents / 1.42±0.79 / 1.41±0.74 / 0.97 / 1.44±0.82 / 1.54±0.91 / 0.004
Total stent length (mm) / 28.8±18.1 / 28.1±16.2 / 0.32 / 28.4±18.3 / 30.9±22.0 / 0.002
Total stent length > 28mm / 392 (31%) / 425 (33%) / 0.45 / 428 (32%) / 374 (36%) / 0.04
Minimum stent size (mm) / 3.1±0.47 / 3.15±0.46 / 0.02 / 3.03±0.49 / 3.1±0.53 / 0.0004
Minimum stent size <3.0mm / 341 (27%) / 283 (22%) / 0.001 / 463 (35%) / 319 (31%) / 0.04
IVUS use / 209 (17%) / 362 (28%) / <0.0001 / 269 (20%) / 337 (33%) / <0.0001
(C) Baseline medication
Medication at hospital discharge
Antiplatelet therapy
Thienopyridine / 1241 (99%) / 1304 (100%) / <0.0001 / 1279 (97%) / 1026 (100%) / <0.0001
Ticlopidine / 1171 (94.5%) / 1163 (90%) / <0.0001 / 1212 (95.1%) / 932 (91.6%) / 0.0007
Clopidogrel / 68 (5.5%) / 136 (10%) / <0.0001 / 62 (4.9%) / 85 (8.4%) / 0.0007
Aspirin / 1252 (99.6%) / 1304 (100%) / 0.008 / 1303 (99%) / 1026 (100%) / <0.0001
Cilostazol / 286 (23%) / 467 (36%) / <0.0001 / 168 (13%) / 158 (15%) / 0.07
Other medications
Statins / 681 (54%) / 717 (55%) / 0.68 / 542 (41%) / 520 (51%) / <0.0001
Beta-blockers / 571 (45%) / 527 (40%) / 0.01 / 268 (20%) / 240 (23%) / 0.08
ACE-I / ARB / 942 (75%) / 954 (73%) / 0.3 / 621 (47%) / 547 (53%) / 0.003
Nitrates / 296 (24%) / 413 (32%) / <0.0001 / 516 (39%) / 452 (44%) / 0.02
Calcium channel blockers / 260 (21%) / 242 (19%) / 0.18 / 703 (53%) / 547 (53%) / 0.99
Nicorandil / 405 (32%) / 404 (31%) / 0.5 / 230 (17%) / 221 (22%) / 0.01
Warfarin / 93 (7.4%) / 142 (11%) / 0.002 / 81 (6.2%) / 62 (6.0%) / 0.92
Proton pump inhibitors/ H2-blockers / 789 (63%) / 946 (73%) / <0.0001 / 538 (41%) / 500 (49%) / 0.0001

Values are expressed as mean ± SD or number (%).

Abbreviations are same as in Supplemental Table 1.

Supplemental Table 3. Event Rates Through 3 Years: SAPT versus DAPT at the 2-Month Landmark Point

SAPT group / DAPT group / Unadjusted / P value / Adjusted / P value
N of patients with events/ N of patients at risk / N of patients with events/ N of patients at risk / Hazard Ratio / Hazard Ratio
(Cumulative incidence) / (Cumulative incidence) / (95% CI) / (95% CI)
CV death/MI/Stroke/definite ST/bleeding
All patients / 231/2422 (9.8%) / 226/2188 (10.6%) / 0.91 (0.76-1.1) / 0.34 / 0.97 (0.79-1.19) / 0.77
AMI / 97/1167 (8.6%) / 106/1207 (9.0%) / 0.94 (0.71-1.24) / 0.66 / 0.99 (0.72-1.35) / 0.93
Non-AMI / 134/1255 (11.0%) / 120/981 (12.6%) / 0.86 (0.67-1.1) / 0.23 / 0.94 (0.72-1.24) / 0.68
CV death/MI/Stroke/definite ST
All patients / 177/2520 (7.3%) / 167/2251 (7.6%) / 0.94 (0.86-1.31) / 0.57 / 0.99 (0.79-1.26) / 0.97
AMI / 82/1217 (7.0%) / 89/1246 (7.4%) / 0.94 (0.69-1.27) / 0.68 / 1.03 (0.72-1.45) / 0.89
Non-AMI / 95/1303 (7.5%) / 78/1005 (8.0%) / 0.93 (0.69-1.26) / 0.65 / 0.99 (0.71-1.37) / 0.94
CV death/MI
All patients / 128/2547 (5.2%) / 110/2287 (4.9%) / 1.04 (0.74-1.24) / 0.75 / 1.06 (0.8-1.1) / 0.68
AMI / 66/1238 (5.5%) / 64/1278 (5.1%) / 1.06 (0.75-1.5) / 0.74 / 1.00 (0.67-1.5) / 0.99
Non-AMI / 62/1309 (4.9%) / 46/1009 (4.7%) / 1.04 (0.71-1.53) / 0.85 / 1.16 (0.76-1.77) / 0.5
GUSTO moderate/severe bleeding
All patients / 102/2468 (4.3%) / 106/2254 (4.9%) / 0.88 (0.67-1.15) / 0.34 / 0.97 (1.72-1.3) / 0.82
AMI / 38/1199 (3.3%) / 43/1255 (3.6%) / 0.92 (0.59-1.43) / 0.72 / 1.01 (0.62-1.64) / 0.98
Non-AMI / 64/1269 (5.2%) / 63/999 (6.5%) / 0.8 (0.56-1.13) / 0.2 / 0.91 (0.63-1.33) / 0.63

Supplemental Appendix A: List of participating centers and investigators for the CREDO-Kyoto PCI/CABG Registry Cohort-2

Cardiology

Kyoto University Hospital: Takeshi Kimura

Kishiwada City Hospital: Mitsuo Matsuda, Hirokazu Mitsuoka

Tenri Hospital: Yoshihisa Nakagawa

Hyogo Prefectural Amagasaki Hospital: Hisayoshi Fujiwara, Yoshiki Takatsu, Ryoji Taniguchi

Kitano Hospital: Ryuji Nohara

Koto Memorial Hospital: Tomoyuki Murakami, Teruki Takeda

Kokura Memorial Hospital: Masakiyo Nobuyoshi, Masashi Iwabuchi

Maizuru Kyosai Hospital: Ryozo Tatami

Nara Hospital, Kinki University Faculty of Medicine: Manabu Shirotani

Kobe City Medical Center General Hospital: Toru Kita, Yutaka Furukawa, Natsuhiko Ehara

Nishi-Kobe Medical Center: Hiroshi Kato, Hiroshi Eizawa

Kansai Denryoku Hospital: Katsuhisa Ishii

Osaka Red Cross Hospital: Masaru Tanaka

University of Fukui Hospital: Jong-Dae Lee, Akira Nakano

Shizuoka City Shizuoka Hospital: Akinori Takizawa

Hamamatsu Rosai Hospital: Masaaki Takahashi

Shiga University of Medical Science Hospital: Minoru Horie, Hiroyuki Takashima

Japanese Red Cross Wakayama Medical Center: Takashi Tamura