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. 7 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. 9 10 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. 11 12 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- 12 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. 13