Dual Antiplatelet Therapy (DAPT) Duration Dilemma: Recent Trials And Guidelines For Clinical Practice Dean J. Kereiakes, MD FACC FSCAI Medical Director, The Christ Hospital Heart & Vascular Center and the Lindner Research Center at The Christ Hospital, Cincinnati, Ohio Professor of Clinical Medicine, Ohio State University Dean J. Kereiakes, MD – Disclosure Information Consulting fees: • Modest: Medpace, HCRI, Ablative Solutions, Inc. • Significant: Boston Scientific, Abbott Vascular, REVA Medical Inc. 2011 ACC/AHA/SCAI Guideline for PCI The duration of P2Y12 inhibitor therapy should generally be as follows: DURATION I IIa IIb III a. In patients receiving a stent (BMS or DES) during PCI for ACS, P2Y12 inhibitor therapy should be given for at least 12 months. Options include clopidogrel 75 mg daily,prasugrel 10 mg daily or ticagrelor 90mg twice daily I IIa IIb III b. In patients receiving DES for non-ACS indication, clopidogrel should be given for at least 12 months if patients are not at high risk for bleeding. I IIa IIb III c. In patients receiving BMS for a non-ACS indication, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless patient is at increased risk for bleeding;then it should be given for a minimum of 2 weeks) Circulation 2011;124:e574-651 3 Randomized Trials of DAPT Duration Trial Patients Test Randomization 1° EP 2701 DES N=20,645 (15,245 DES) (5,400 BMS) N=1,800 DES, BMS 1 vs. 2 yrs A vs. A+C Superiority A+P vs. DAPT (clop or pras) NI and Sup A vs. A+C Superiority D/MI 2 yrs after rand D/MI/TVR Prolonged DAPT Studies REAL/ZEST Late DAPT PRODIGY 1 vs. 2.5 yrs* 6 mos vs. 2 yrs D/MI/CVA ST, Bleeding D/MI/CVA Abbreviated DAPT Studies EXCELLENT ISAR-SAFE** N=1,443 SES and EES N=6,000 DES 6 vs. 12 mos* A vs. A+C Noninferiority A+P vs. A+C Noninferiority N=3,700 EES 6 vs. 12 mos A vs. A+C Noninferiority D/MI/CVA/ ST/TIMI MB D/MI/CVA/ Urg Revasc/MB N=3,120 ZES N=2,148 E-ZES vs RZES, SES, EES 3 vs. 12 mos A vs. A+C Noninferiority D/MI/CVA/MB 3 vs. 12 mos A+C vs. A+C CVD/MI/ST/ ID-TVR, Bleed ITALIC OPTIMIZE RESET‡ ‡Strategy not DAPT duration **2014-2015 6 vs. 12 mos *Plus a 3 month washout period Correlation of Clopidogrel Therapy Discontinuation in REAL-world Patients Treated with Drug-Eluting Stent Implantation and Late Coronary Arterial Thrombotic Events: REAL-LATE Trial Patients on current dual antiplatelet therapy without MACCE or major bleeding for at least the first 12 months after DES implantation (Total N~2,700) 1:1 randomization Stratified by (1) centers (2) Initial DES types Aspirin + clopidogrel Dual-therapy (N=1,000) Aspirin Mono-therapy (N=1,000) Regular Clinical assessment after randomization Primary end points: The composite of cardiac death or MI PRODIGY Study: 6 vs 24m DAPT after DES or BMS, randomized at 30 days 2,013 randomly allocated to recieve one of the four study stent types 499 randomized to and received EES 498 randomized to and received PES 500 randomized to and received ZES 502 randomized to and received BMS (1497 DES) 694 Excluded, 353 Not Meeting Inclusion Criteria 232 Refused to Participate, 109 Operator’s choice 1,970 DES and BMS randomized at 30 days 983 BMS 30d treatment allowed and counted as 6m 6 Months DAPT Ff 984 f 2 year follow-up Not blinded Primary EP Death,MI,CVA 987 24 Months DAPT Ff 979 f 2 year follow-up Valgimigli, M., et al., Circulation, 2012. EXCELLENT Trial Design Prospective, open label, two-arm, randomized multi-center trial 1372 Patients Matching Enrollment Criteria 19 centers in Korea Everolimus-Eluting Stent N=1029 DAT 6 mo DAT 12 mo N=515 N=514 Randomization 3:1 Sirolimus-Eluting Stent 2x2 factorial design DAT 6 mo DAT 12 mo N=171 N=172 N=343 Percutaneous Coronary Intervention clinical endpoint evaluation Clinical 1mo Angiographic *CD,MI,IDTVR 3mo 9mo 12mo Primary endpoint: In-segment LL TVF* 2yr 3yr 4yr 5yr Am Heart J 2009 May;157:811-817.e1. Gwon et al. Circ. 2012;125:505-513 7 OPTIMIZE STUDY 3,120 minimally selected* patients undergoing PCI with E-ZES in 33 sites in Brazil Randomization ** (1:1) DAPT for 3 months N = 1,560 DAPT for 12 months N= 1,560 Clinical FU at 1, 3, 6, 12 and 18 months and yearly up to 3 yrs Primary endpoint: Net Clinical Benefit † at 12-month FU Feres et al. AHJ 2012:164:810 e3 Feres et al. TCT 2013 LBCT * Exclude ACS with + biomarker; prior DES Rx;SVG target ** Stratified by DM and Institution; not blinded † composite endpoint of all-cause death, MI, CVA and major bleeding Ischemic Endpoints By DAPT Duration In Randomized Trials EXCELLENT t 12 6 mos (n=957) 12 mos (n=970) 8.4 12 mos (n=1344) 24 mos (n=1357) 3 mos (n=1563) 12 mos (n=1556) 10 10.1 8.9 8.4 7.5 8 % Patients OPTIMIZE tttt REAL-LATE/ ZEST-LATE ttt 6 mos (n=1546) 24 mos (n=1500) 9.6 10 6 PRODIGY tt 7.5 4.7 4.4 4.6 4 4.1 3.2 1.7 2 2.3 1.8 0 TVF* MACCE** *Cardiac death / MI / TVR **Death / MI, CVA, Revasc ***Death/MI/Revasc D/MI D/MI/CVA D/MI Adapted from D/MI/CVA Cardiac MACE*** D/MI t Gwon et al. ACC 2011 tt Valgimigli et al. ESC 2011 ttt Park et al. NEJM 2010;362:1374 tttt Feres et al. TCT 2013 LBCT Major Bleeding (TIMI or GUSTO/REPLACE 2* ) By DAPT Duration In Randomized Trials EXCELLENT t 3 2.5 6 mos 12 mos PRODIGY tt 6 mos 24 mos P=0.42 REAL-LATE/ ZEST-LATE ttt 12 mos 24 mos P=0.04 OPTIMIZE tttt* 3 mos 12 mos P=0.35 P=0.66 % Patients 2 1.6 1.5 1 0.6 0.5 0 0.3 0.7 0.6 0.1 Adapted from 0.8 0.2 t Gwon et al. ACC 2011 tt Valgimigli et al. ESC 2011 ttt Park et al. NEJM 2010;362:1374 tttt Feres et al. TCT 2013 LBCT Type II, III or V BARC Bleeding: PRODIGY CEC adjudicated 24 mo DAPT 6 mo DAPT P=0.00018 % 7.4 3.5 Hazard ratio: 0.46 (0.1-0.69) 0 0 180 360 540 720 No. at Risk 24-month clopidogrel 987 925 884 6-month clopidogrel 983 919 881 Valgimigli et al. Circulation 2012; 125:2015-2026 PRODIGY BARC Bleeding Categories 10 24 mo DAPT 6 mo DAPT 8 % 6 4 P=0.001 P=0.075 4.0 P=0.029 2.5 2 1.5 1.4 0.9 0.5 0 BARC 2* BARC 3 BARC 5 *BARC 2 “Any overt, actionable sign of hemorrhage that…meets 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…no change in hemoglobin, blood transfusion or hemodynamic sequelae are required” Mehran et al. Circ 2011;123:2736-2747 OPTIMIZE : NACCE at 1 Year (All-Cause Death, MI, Stroke, Major Bleeding) Cumulative Incidence of NACCE (%) 15 3M DAPT 12M DAPT Log-Rank P = 0.838 10 6.0 5.8 5 0 0 3 6 9 Time After Initial Procedure (Months) 12 No. at risk 3M DAPT 12M DAPT 1563 1556 1520 1514 1504 1497 1468 1466 1384 1381 Feres et al. TCT 2013 LBCT Primary Endpoint: NACCE at 1 Year (All-Cause Death, MI, Stroke, Major Bleeding) 3M DAPT 12M DAPT (N = 1563) (N = 1556) 6.1% 5.9% Difference Upper 1-sided 95% CI : 0.2% Non-inferiority P value : 2.0% = 0.002 Zone of non-inferiority Pre-specified margin = 2.7% Non-inferior -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 % Upper one-sided 95% CI Primary Non-Inferiority Endpoint Met OPTIMIZE :Other Clinical Events at 1 Year* 3 Months DAPT (N = 1563) Bleeding / Safety Ischemic / Efficacy 12 10 12 Months DAPT (N = 1556) 12% 8.4 Events (%) 8 7.5 12% 6 14% 4 3.2 4.6 9.4% 4.1 2.8 3.5 3.2 2 12.5% 0.7 0.8 0 MACE MI *All P=NS Cardiac Death/MI TLR Major Bleed Feres et al. TCT 2013 LBCT OPTIMIZE: Stent Thrombosis* vs. Major Bleeding Major Bleeding ARC Def./Prob. Stent Thrombosis Cumulative Incidence (%) 3M DAPT 12M DAPT P = 0.64 HR 0.81 (0.34-1.96) 5 P = 0.18 HR 3.97 (0.44-35.49) ~4x 0 0.7 0.6 0 3 6 9 0.26 0.07 Cumulative Incidence (%) 10 10 12 Time After Initial Procedure (months) *0.2% absolute difference 3M DAPT 12M DAPT 5 P = 0.79 HR 0.87 (0.32-2.40) P = 0.31 HR 0.50 (0.12-1.99) 2x 0 0 3 6 0.4 0.2 9 Time After Initial Procedure (months) Feres et al. TCT 2013 LBCT 12 RESET 2,148 patients enrolled and randomized Divided into 4 subsets and 1:1 randomization was performed E-ZES with 3-month DAPT Standard Therapy Other DES with 12-month DAPT 31 patients excluded - 16 withdrawal of consent - 15 Met exclusion criteria E-ZES with 3-month DAPT (N=1059) Diabetes mellitus Subset (N=292) E-ZES (N=146) R-ZES (N=146) Acute coronary syndrome Subset (N=601) E-ZES (N=301) R-ZES (N=300) Primary Endpoint: CV death, MI, ST, ID-TVR, Bleed (TIMI major & minor) Standard therapy (N=1058) Short-length DES Subset (N=681) E-ZES (N=341) SES (N=340) Long-length DES Subset (N=543) E-ZES (N=271) EES (N=272) Kim et al. JACC 2012;60:1340-1348 RESET: Clinical Events Through 1 Year E-ZES + 3 month DAPT (n=1,059) 5 4.7 4.7 Standard Therapy (n=1,058) Adapted from Kim et al. JACC 2012 Sep 5 (e-Pub ahead of print) % Patients 4 3 2 1.3 0.8 1 0 40 41 CV Death, MI, ST, ID-TVR, Bleed* 8 0.6 11 Death, MI, ST 0.2 0.3 0.2 2 3 2 Def/Prob ST** 6 Major Bleed *Primary Endpoint: (Assumed 10% with N.I. margin 4% for absolute difference in risk) **SORT OUT III / ENDEAVOR IV / PROTECT / KAMIR ISAR-SAFE Study Flowchart -8th to Drug- Eluting Stenting -5th Continuous Clopidogrel therapy for 5 to 8 months Randomization 0 Clopidogrel 75 mg/d for 6 months Placebo for 6 months Follow Up 1st 6th 9th 1st FU: 1 month after randomization 2nd FU: 6 months after randomization (at least one day after study drug cessation) 3rd FU: 9 months after randomization (at least 3 months after study drug cessation) PEP = death,MI,stent thrombosis,stroke,TIMI major bleed DAPT: Study Design Eligible for Enrollment after PCI •Any PCI with DES or BMS •>18 years of age •No contradictions to dual antiplatelet therapy •Able and willing to provide written informed consent Not Eligible for Randomization at 12 m Eligible for Randomization at 12 m Stratified by DES v BMS, drug type, and complexity (ACS or lesion-based) 18 12 m DAPT Arm 30 m DAPT Arm mos Aspirin + blinded placebo Aspirin + blinded thienopyridine Study treatment period 12-30 m Study observation period 30-33m Total 33 month follow-up • Death • MI or repeat PCI at > 6 weeks • CABG • Stroke • Major Bleed Total 33 month follow-up Primary analysis DES treated subjects, 12-30m Secondary analysis propensity matched BMS to DES subjects 0-30m 2 co-primary endpoints: stent thrombosis and MACCE (death, myocardial infarction or stroke) Powered safety endpoint: major bleeding (GUSTO) Mauri, Kereiakes et al AHJ 2010;160:1038-1041 20 Thienopyridine Type: DAPT Study All Randomized Subjects; N = 11,649 32 68 Clopidogrel Prasugrel Stent Type: DAPT Study All Randomized Subjects N = 11,649 DES Type* N = 9,961 14 86 DES BMS Cypher (n=1,196) 12.0% Endeavor (n=1,310) 13.1% TAXUS (n=2,786) 28.0% Xience/PROMUS (n=4,874) 48.9% *Some patients received more than one DES type Complexity Amongst Randomized Subjects: DAPT *clinical =ACS, renal insufficiency LVEF <30% **anatomic=UPLM; >3 vessels; >2 lesions/vessel; LL ≥30mm; bifurcation; DES ISR; SVG; thrombus; VBT Cumulative incidence rate (%) EXCELLENT Trial: Target Vessel Failure 6-mo DAT 12-mo DAT P=0.507 HR = 1.17 (95% CI 0.73-1.89) 4.7% 4.4% Months after initial procedure Patient Number at Risks 6-month 722 707 701 697 681 12-month 721 710 699 698 680 Am Heart J 2009 May;157:811-817.e1. TVF According To Diabetes And DAPT Duration: EXCELLENT Non-diabetics Diabetics p=0.022 HR = 0.42 (95% CI 0.20-0.88) 6-mo DAT 12-mo DAT p=0.005 8.8% HR = 3.15 (95% CI 1.41-7.01) 5.2% 2.9% 2.2% Patient Number at Risk Patient Number at Risk 6-mo 450 446 445 443 437 272 261 259 255 245 12-mo 443 435 432 429 416 278 275 271 270 265 Gwon et al,ACC 2011 LBCT 6 vs. 12 months DAPT After DES: EXCELLENT Total 6 mo DAPT n (%) 12 mo DAPT n (%) HR (95% CI) P value Interaction P-value Age <65 767 19 (5.1) 12 (3.2) 1.61 (0.78-3.31) 0.20 ≥65 676 15 (4.5) 18 (5.5) 0.83 (0.42-1.65) 0.59 No 699 21 (6.03) 13 (3.82) 1.61 (0.8-3.21) 0.18 744 13 (3.65) 17 (4.69) 0.78 (0.38-1.60) 0.50 Diabetes No 893 10 (2.27) 22 (5.08) 0.44 (0.21-0.94) 0.03 Yes 550 24 (9.09) 8 (2.96) 3.16 (1.42-7.03) 0.005 LVEF ≥50% 1097 26 (4.91) 24 (4.42) 1.12 (0.64-1.95) 0.69 124 2 (3.08) 4 (7.41) 0.41 (0.07-2.23) 0.30 0.27 1079 25 (4.72) 26 (4.94) 0.96 (0.55-1.66) 0.89 0.18 364 9 (5.14) 4 (2.27) 2.31 (0.71-7.5) 0.16 ACS Yes <50% Stent type EES SES 0.19 0.15 <0.001 0.125 0.25 0.5 1 2 4 8 Favors 6 mo DAPT Favors 12 mo DAPT Gwon et al. Circulation 2012;125:505-13 Clopidogrel Duration after PCI in Diabetics*: Death and Non-Fatal Myocardial Infarction < 6 months 6-9 months Cumulative Incidence (%) 25 25 Composite of death & MI p <0.001 20 Death 15 10 10 5 5 0 90 # at risk < 6 mos 261 6- 9 mos 117 > 9 mos 371 180 270 360 450 540 630 Time (days) 234 113 358 222 106 356 174 83 286 *749 consecutive diabetic patients/Kaiser L.A. p < 0.001 20 15 0 > 9 months 0 0 90 261 117 371 180 270 360 450 Time (days) 239 116 362 231 111 361 540 630 186 88 293 Brar et al. JACC 2008;51:2220 Stent Type and Clopidogrel Duration After PCI in Diabetics: Death and Non-Fatal Myocardial Infarction w/ clopidogrel w/o clopidogrel Cumulative Incidence (%) 20 w/ clopidogrel w/o clopidogrel 10 15 BMS DES landmark-left censored landmark-left censored 10 P=0.01 P=0.07 5 5 0 0 0 90 180 270 360 450 540 630 Time (days) # at risk BMS with clop 147 BMS w/o clop 74 145 67 139 64 0 90 # at risk DES with clop DES w/o clop 180 270 360 450 Time (days) 323 127 312 125 540 630 220 83 Brar et al. JACC 2008;51:2220 Multivariate Analysis Predictors of BARC Bleeding Events on DAPT* OR (95% CI) Female P 2.7 (1.8-4.1) <0.001 Non-diabetic 1.9 (1.2-3.1) VLTPR (VASP≤10%) 0.005 4.7 (2.7-8.3) <0.001 -2 1 2 4 6 8 10 *1,542 patients (clopidogrel 1155; prasugrel 387) Adapted from Cuissett et al. JACC Card Int 2013;6:854-863 Stent Thrombosis Stratified by Clinical Syndrome and Stent Type 5 5 ACS vs SA logrank p<0.0001 4 3 4 BMS: SA vs. ACS logrank p=0.01 DES: SA vs. ACS logrank p=0.0007 SA: BMS vs. DES logrank p=0.2 ACS: BMS vs. DES logrank p=0.06 DES, ACS 3 ACS BMS, ACS 2 2 DES, SA 1 BMS, SA 1 SA 0 0 0 6 12 18 24 Time (months) N=5,816 30 36 0 6 12 18 24 30 Time (months) Kukreja et al. JACC Intv 2009;2:534 36 Analysis of DAPT Duration Beyond 1 Year Following PCI for AMI*: COREA-AMI Registry % Patients Death, NFMI, Stroke 25.0 20.0 P<0.001 for trend 18.0 15.0 10.2 10.0 8.9 5.0 0.0 12-18 months 18-24 months >24 months *2293 consecutive patients MACCE + major bleed free at 1 year post-MI Koh et al. JACC 2013;61:A40 (abstract E161; presentation 1255M-178) Mortality Following PCI for ACS by Clopidogrel Use: Veterans Administration 2003-2004* Cumulative mortality rate 0.2 0.15 0.1 0.05 Off clopidogrel On clopidogrel 0 0 90 180 270 360 450 540 630 720 Follow-up time, days *n=1455 (66% BMS, 34% DES) HR BMS 2.65; DES 2.0 Ho et al. Am Heart J 2007;154:846 Freedom from Cardiac Death, M I and Revasc Target And Non-target Lesion MACE* After Stenting In 1,057 Patients (Sirius Trial) % Target Vessel 100 100 90 90 80 72.3% 80 70 57.1% 70 60 50 Non-target Vessel % 74.3% 74.2% 60 SES BMS Log-Rank p<0.001 40 SES BMS 50 Log-Rank p=0.096 40 0 360 720 1080 1440 1880 Time after Initial Procedure (days) *CV Death, M I, Revasc 0 360 720 1080 1440 1880 Time after Initial Procedure (days) Chacko, Cutlip et al. JACC Intv 2009;2:498 CHARISMA: Dual Therapy Vs. ASA Monotherapy In Symptomatic* Patients CD / MI / Stroke *Prior MI, CVA or symptomatic PAD Bhatt et al. JACC 2007;49:1982-1988 Failure rate Failure rate Death / MI Events Following Clopidogrel Discontinuation After SVG PCI Sachdeva et al. JACC 2012; Oct 25 [Epub ahead of print] Cumulative incidence of D / MI / CVA (%) Stenting for ISR: PRODIGY Substudy 0.85 short DAPT regimen (n=114) long DAPT regimen (n=110) 0.90 0.95 P=0.034 1.00 0 60 120 180 240 300 360 420 480 540 600 660 720 Time (days) Campo et al. JACC 2013 prepub Definite Stent Thrombosis Through 3 Years In 18,334 Patients (28,739 Lesions) By Stent Type 3-Year Incidence of Stent Thrombosis BMS 1G-DES 2G-DES Stent Thrombosis (%) Stent thrombosis (%) 3.0 2.5 2.0 1.5 1.0 1-Year Landmark Analysis 3.0 2.5 2.0 1.5 1.0 0.5 0.5 0.0 0.0 0 1 2 Years after procedure 3 BMS 1G-DES 2G-DES 0 1 2 Years after procedure Tada, Kastrati et al. JACC INTV 2013; 6:1267-74 3 Clinical Outcomes By Statistical Model, Duration of DAPT And Follow-Up: Meta Analysis of 13 RCCT Involving 17,097 Patients TVR Stent Thrombosis MI Statistical Model Random (13) Fixed (13) Clopidogrel Duration 6 months (5) 12 months (7) Follow-up Duration ≤ 1 year (12) > 1 year (7) Favors .1 EES 1 10 Non-EES 0.4 EES 4 0.4 Non-EES EES Baber et al. JACC 2011;58:569-77 4 Non-EES Long-term Risk Of Def/Prob Stent Thrombosis: Network Meta-Analysis Of 76 RCCT* Control BMS (Ref) Treatment Treatment Control Odds Ratio 95% CrI Sirolimus Paclitaxel Everolimus Zotarolimus Zotarolimus-R 0.80 1.11 0.46 0.69 0.62 0.61 0.85 0.31 0.39 0.29 1.10 1.49 0.70 1.28 1.44 Paclitaxel Everolimus Zotarolimus Zotarolimus-R 1.38 0.57 0.87 0.78 1.02 0.39 0.48 0.35 1.84 0.84 1.50 1.73 Everolimus Zotarolimus Zotarolimus-R 0.41 0.62 0.56 0.29 0.35 0.26 0.60 1.11 1.25 Zotarolimus Zotarolimus-R 1.52 1.36 0.77 0.68 2.83 2.71 Zotarolimus-R 0.91 0.36 2.40 Sirolimus (Ref) Paclitaxel (Ref) Everolimus (Ref) Zotarolimus (Ref) 0.10 1.0 * >86% probability that EES has lowest rate of “any” stent thrombosis 10.0 Bangalore et al. Circ 2012;125:2873-91 Network Meta-Analysis of 49 Trials Involving 50,844 Patients Late definite or probable thrombosis ds rtio (95% CI) CoCr-EES vs BMS 0.42 (0.17-0.95) CoCr-EES vs PES 0.33 (0.15-0.71) CoCr-EES vs R-ZES 0.24 (0.05-0.94) CoCr-EES vs E-ZES 0.19 (0.04-0.75) SES vs PES 0.41 (0.17-0.90) PC-ZES vs SES 4.31 (1.08-19.05) 0.01 0.1 Favors stent 1 1 10 100 Favors stent 2 Palmerini et al. Lancet 2012;379:1393-1402 DAPT Duration: Conclusions 1. “One size shoe” approach for DAPT duration is unlikely to fit all patients • • • ACS Diabetes CABG-SVG / ISR We treat symptomatic patients and non-target lesions with objective to reduce events (D/MI/CVA) which may not be stent (target lesion) related 3. Stent platforms differ with respect to risk for early , late and/or very late stent thrombosis events (“All DES not created equal”) 4. Conclusions regarding “optimal” DAPT duration should be based on adequately powered RCCT 2. Stent Thrombosis and DAPT Interruption Through 2 Years: Pooled Analysis of SPIRIT II-V; WOMEN; XV USA/India Analysis population 11,219 / 13,259 (84.6%) pts complete DAPT data to 2 years 85 events in 83 pts (0.74%) through 2 years 45 ST events occurred in 44 pts with no DAPT interruption from day 1 through 2 yrs 40 ST events occurred in 39 pts with some DAPT interruption from day 1 though 2 yrs 45 events occurred “On” DAPT* 23 events occurred “On” DAPT 17 events occurred “Off” DAPT ►68/85 ST events (80.0%) occurred “On” DAPT *One patient did not receive loading lose and was off DAPT at ST event (day 0) but started day 1 and never interrupted through 730 days. Stone et al. JACC 2011;58(Suppl B):78