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