DAPT Duration after Stenting: An Updated Appraisal

Transcription

1 DAPT Duration after Stenting: An Updated Appraisal 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

2 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Modest Consulting Fees Modest Consulting Fees Significant Consulting Fees Significant Consulting Fees Significant Consulting Fees Significant Consulting Fees Significant Consulting Fees Major Stock Shareholder/Equity Company HCRI SINO Medical Sciences Technologies, Inc. Boston Scientific Corporation Abbott Vascular Svelte Medical Systems, Inc. Micell Technologies, Inc. Caliber Therapeutics Ablative Solutions, Inc.

3 2016 ACC/AHA Guideline Focused Update on DAPT Duration: Patients With SIHD Treated on Dual Antiplatelet Therapy In patients with SIHD after BMS implantation, P2Y12 I A COR LOE Recommendations I A inhibitor therapy with clopidogrel should be given for In patients with SIHD after BMS implantation, P2Y12 inhibitor therapy a minimum of 1 month. with clopidogrel should be given for a minimum of 1 month. In with SIHD after DES implantation, P2Y12 inhibitor therapy with I B-R SR In patients with SIHD after DES implantation, P2Y12 I B-R SR clopidogrel should be given for at least 6 months. inhibitor therapy with clopidogrel should be given for at least 6 months. In patients treated with DAPT, the recommended daily dose of aspirin is 81 I B-NR mg (range, 75 mg to 100 mg). IIb A SR In patients with SIHD after BMS or DES implantation who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk (e.g., prior bleeding on DAPT, coagulopathy, oral anticoagulant use), continuation of DAPT with clopidogrel for longer than 1 month (BMS) or longer than 6 months (DES) IIb A SR In patients with SIHD after BMS or DES implantation who IIb C-LD have tolerated DAPT without a bleeding complication may be reasonable. and who are not at high bleeding risk (e.g., prior bleeding on DAPT, coagulopathy, oral anticoagulant use), continuation of DAPT with clopidogrel for longer than 1 In patients with SIHD after DES implantation who develop high risk of bleeding (e.g., treatment with oral anticoagulant therapy), reasonable. are at high risk of severe bleeding complication (e.g., major intracranial surgery), or develop significant overt bleeding, discontinuation of P2Y12 inhibitor therapy after 3 months may be reasonable. month (BMS) or longer than 6 months (DES) may be Levine, Bates, Bittle, et al. JACC 2016 (epub)

4 BMS vs. 1 st GEN DES vs. 2 nd GEN DES: Definite Stent Thrombosis SCAAR* BMS 1G-DES 2G-DES ISAR-Munich** Stent thromb bosis (%) G-DES MONTHS YEARS *Sarno et al. EHJ 2012; 33:606 94,384 Consecutive PCI **Tada, Kastrati et al. JACC CI 2013; 6: ,334 Patients; 28,739 Lesions

5 Propensity-Matched DES vs. BMS (n=10,026 pts) Risk Difference for Stent Thrombosis 0-33 months Stent Throm mbosis* Cumulative Incidence of No. At Risk 20% 15% 10% 5% 0% DES BMS 0-12 Months: RD -1.00% 0.70% vs. 1.68% P=0.002 (Difference) 0-33 Months: RD -1.05% 1.70% vs. 2.61% P<0.001 (Non-inferiority) P=0.01 (Difference) Months After Enrollment DES BMS Kereiakes D, et al. JACC CI. 2016;9: *Weighted Kaplan-Meier and risk differences (RD) are presented 10,026 patients matched perfectly for STEMI and <10% variance for 55 total variables 5

6 Propensity Matched Weighted RD vs. BMS by DES Type: 0-33 Months Abbreviations: EES, everolimus-eluting stent; SES, sirolimus-eluting stent; PES, paclitaxel-eluting stent; ZES, zotarolimus-eluting stent (Endeavor). Kereiakes D, et al. JACC CI. 2016;9:

7 Stent Thrombosis by Randomly Assigned Stent: PRODIGY* (502) (500) (500) (501) PES BMS ZES * CD / TVMI / IDLTR EES *stent and DAPT duration (3 vs 12 months) randomized Valgimigli et al. JACC Intv 2014:7:20-8

8 NORSTENT: Current DES vs. BMS in More-comers * * 21,000 PCI 12,425 eligible / 9013 enrolled + randomized 3202 eligible patients (>25%) excluded for doctor preference/unknown Bonaa, et al. NEJM 2016

9 Meta-Analysis of 5 RCCT (4896 Patients) EES versus BMS Stent Thrombosis TVR Valgimigli et al. BMJ 2014;349:g6427

10 Summary of Network Meta-Analyses of RCT for Late + Very Late Def / Prob ST by Stent Type Study ODDS RATIO [95% CI] Palmerini (Lancet 2012) 0.39 [0.23, 0.69] 49 RCT/50,844 pts 2 yrs follow-up 0.46 [0.31, 0.70] Bangalore (CIRC 2012) 76 RCT/120,000 pt-yrs 0.32 [0.21, 0.48] Kang (EHJ 2014) 113 RCT/90,584 pts 0.35 [0.17, 0.69] Palmerini (JACC CI 2013) 2 yrs follow-up FAVORS EES FAVORS BMS

11 DAPT Trial: Stent type stratified at randomization BMS randomized treatment duration (30 vs 12 mos) by stent type interaction ARC definite/ probable ST 30 Month DAPT 12 Month DAPT Stent Type N (%) N (%) DES (N=9961) 19 (0.4%) 65 (1.4%) HR (95% CI) 0.29 ( ) BMS (N=1687) 0.49 ( ) 4 (0.5%) 9 (1.1%) Kereiakes, Yeh Massaro et al., JAMA 2015; 313:1113 P Value Interaction 0.42 * *consistent treatment effect benefit 11

12 ZEUS Trial*: HBR Population LEADERS Free ACS Substudy** HBR Patients Ariotti S, et al. JACC CI 2016;9(5): *stent randomized/ 30 days DAPT Naber, et al. Eur Heart J 2016 (epub) **stent randomized/ 30 days DAPT

13 LEADERS FREE: Primary Safety Endpoint (Cardiac Death, MI, ST) at 2 year Patients with Event (%) % 12.7% % % 5 HR 0.80 (95%CI ) p = Days DCS BMS Number at Risk 2 year FU was obtained at 730 days Garot, Urban et al. JACC 2017;69: days

14 LEADERS FREE: Primary Efficacy Endpoint (Clinically-Driven TLR) at 2 Years Patients with Event (%) % 9.3% % 5 4.9% HR 0.54 (95%CI = ) P< Days DCS BMS Number at Risk 2 year FU was obtained at 730 days + 60 days Garot, Urban et al., JACC 2017;69:162-71

15 LEADERS FREE: Multivariate Predictors of Primary Safety Endpoint and Major Bleeding (BARC 3-5) Cardiac death/mi/st Major Bleeding Congestive heart failure 1.61 ( ) p=0.001 Multivessel disease 1.66 ( ) p< Number of stents / patient (per stent) 1.20 ( ) p< BMS (vs. DCS) 1.28 ( ) p= Age > ( ) p< ( ) p=0.006 Haemoglobin (per 1 mmol/l lower)* 1.32 ( ) p< ( ) p<0.001 Serum creatinine > 150 umol/l ( ) p=0.012 Planned oral anticoagulants ( ) p<0.001 * Below 9 mmol/l (145 g/l) Garot, Urban et al., JACC 2017;69:162-71

16 SENIOR Trial Design Randomized, prospective, multicenter, single-blind trial Patients 75 years old with 1 stenosis suitable for PCI and with 1 of the following: silent ischemia, stable angina, or ACS, N=1200 Randomized SYNERGY (n=600) REBEL BMS (n=600) DAPT: ASA + Clopidogrel, Prasugrel, or Ticagrelor 1 month for stable angina or silent ischemia 6 months for ACS patients Primary Endpoint: Composite measure of MACCE* at 1 year Secondary Endpoints: *All-cause ARC Def/Prob ST and bleeding** at 1 year Individual components of MACCE*, TLR, TVR, non-tvr at 1 and 2 years Complete anatomic revascularization at baseline procedure Quality of life at 30 days, 6 months, 1 and 2 years Medico-economic analysis at 1 and 2 years mortality, non-fatal MI, stroke, ischemia-driven TLR; **BARC Type 2, 3 and 5; Direct comparison of medical care costs; Varenne, O., et al. EuroIntervention 2017

17 SENIOR: Synergy vs. Rebel BMS with short DAPT (MACCE) Olivier Varenne TCT 2017 LBCT

18 Predictors of Definite Stent Thrombosis: The Dutch Stent Thrombosis Registry* HR 95% CI P value Clop stop < 30 d P< Undersizing P< Clop stop days P= Clop stop days P= Malignancy P< CAD>50% proximal of culprit P< TIMI flow post-pci < P< Dissection P= Bifurcation stenting P= LVEF < 30% P= PAD P= CAD 50% distal of culprit P= No ASA P= Any DES P= DM P= HR P= Age (per 10 yrs) *n= 437 / 21,009 total patients (2.1%) definite ST (62% BMS) Van Werkum et al. JACC 2009;53:1399

19 Meta-analysis : Heterogeneity by Stent Type Giustino et al. JACC 2015;65:

20 ST after thin Strut BP-DES versus DP-DES Meta-Analysis of 9 RCCT (8555 patients)* BP-DES Study or Subgroup DP-DES Weight Risk Ratio Risk Ratio M-H, Fixed, 95% CI M-H, Fixed, 95% CI Events Total Events Total BIOFLOW-II BIOSCIENCE % 0.79 [0.53, 1.19] CENTURY II % 1.00 [0.29, 3.43] DESSOLVE II % 0.51 [0.03, 8.06] EVOLVE FHU EVOLVE II % 0.59 [0.14, 2.48] ISAR-TEST % 0.84 [0.37, 1.90] TARGET I XU et al % 2.79 [0.11, 67.91] % 0.81 [0.58, 1.13] Thin Struts Subtotal (95% CI) Total events Not estimable Not estimable Not estimable 70 Heterogeneity: Chi2=0.99, df=5 (p=0.96); I2=0% Test for overall effect: Z=1.23 (p=0.22) Favors BP-DES El-Hayek, Samady et al. JACC CI. 2017; 10: Favors DP-DES *Biomatrix/ Nobori 1st Gen BP-DES excluded

21 MACCE,revasc, Major bleed free Kedhi, et al. TCT 2017

22 DAPT STEMI: Primary Endpoint (N=433) (N=437) ST (0.9%) (0.7%) Kedhi, et al. TCT 2017

23 RESOLUTE Global Clinical Program Analysis Includes All Available DAPT Data RESOLUTE1 Non--RCT First Non First--in in--human (R=139) 5 yr RESOLUTE AC2,3 1:1 RCT vs. Xience V EES (R=1140; (R=1140; X=1152) 4 yr RESOLUTE Int4,5 Non--RCT Observational (R=2349) Non 3 yr mm Non Non--RCT vs. Hx Control ((R=1402) R=1402) 4 yr mm Non Non--RCT (R (R=100 =100)) vs. Hx Control 3 yr 2.25 NonNon-RCT vs. PG ((R=65) R=65) 2 yr 38 mm subsub-study NonNon-RCT vs. PG (R=114) 1 yr 1:1 RCT vs vs.. Taxus PES (R=200; (R=200; T=200) 1 yr RESOLUTE Asia7 Non--RCT Observational ((R=312) Non R=312) 1 yr R-China Registry9 Non--RCT Observational ((R=1800 Non R=1800)) 1 yr RESOLUTE US6 RESOLUTE Japan R-Japan SVS RESOLUTE US7 R-China RCT8 Enrolling / Planning RI--US Registry RI PROPEL 1 Meredith Post--approval study (RI Post (RI 230) enrolling Post--approval study (RI=1200) vs. Hx Control Post 2 Serruys 3 Silber enrolling IT, et al. EuroIntervention. 2010;5: PW, et al. N Engl J Med. 2010;363: S, et al. Lancet. 2011;377: FJ, et al. EuroIntervention. 2012;7(10): Belardi JA, et al. J Interv Cardiol. 2013;26(5): Yeung AC, et al. JACC. 2011;57: Lee M, et al. Am J Cardiol. 2013;112(9): Xu B, et al. JACC Cardiovasc Interv. 2013;6(7): Qiao S, et al. Am J Cardiol doi: /j.amjcard [Epub ahead of print] 4 Neumann For OMA Distribution Only. Trademarks may be registered and are the property of their respective owners Medtronic, Inc. All Rights Reserved DOC_1A 3/14 Enrollment Complete - In Follow Up

24 RESOLUTE Pooled DAPT (3 (3-Days or more) Stent Thrombosis By Timing of DAPT Interruption Subsequent ARC Def//Prob Stent Thrombosis (%) Timing of First DAPT Interruption ( 3 days) and Subsequent ST Through 1 Year All DAPT Interruptions ( 3 days) and discontinuations No Interruption Interruption Interruption 0-1 Mo 1-12 Mo Pts at risk # of events Median days to interruption NA For OMA Distribution Only. Trademarks may be registered and are the property of their respective owners Medtronic, Inc. All Rights Reserved DOC_1A 3/14

25 Meredith EVOLVE Primary Endpoint TCT 2011 San Francisco, CA Slide 25

26 Meredith EVOLVE Primary Endpoint TCT 2011 San Francisco, CA Slide 26

27 Patient Flow and Stent Thrombosis Through 2 Years: Pooled Patient level analysis 13,259 total pts Analysis population 2,040 pts (15.4%) without complete DAPT data (11 ST events, 0.54%) 11,219 pts (84.6%) with complete DAPT data through 2 years (follow--up rate 94.3%) (follow 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 68/85 ST events (80.0%) occurred On DAPT* 17 events occurred Off DAPT SE Rev. A *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.

28 Stent Thrombosis By Timing of DAPT Discontinuation: Patient Level Analysis of SII-V, Spirit Woman; XV USA; XV India (n=11,219)* Genereux, Stone, et al. Circ CI 2015;8:e *Propensity Adjusted Multivariable Risk of ST during 2 years follow-up

29 Ischemic Outcomes by Treatment: DAPT Study months months* months *Subjects randomized at 12m and discontinued study drug at 30 months Yeh, Mauri, Kereiakes. JACC 2015;65: CV Death 9 vs 2 after discontinuation

30 Monthly cumulative incidence of MI by time period and randomized treatment arm: all randomized (n= 11648) ** * 3x 2x Stefanescu et al. Circulation 2017;135:

31 Monthly cumulative incidence of MI by time period and randomized treatment arm: excluding PES (n= 8864) Continued Thienopyridine Placebo ** * Monthly Cumu M mulative Incid dence of MI 0.5% 0.4% p= % 0.27% p= 0.91 p= % 0.18% 0.17% 0.17% 0.1% 0.13% 0.12% Randomized Treatment Period Aspirin Only Period 0.0% 12M 15M Thienopyridine Discontinuation in Placebo Group Months After Index PCI 30M 33M Thienopyridine Discontinuation in Continued Thienopyridine Group Stefanescu et al. Circulation 2017;135:

32 Use of PRECISE-DAPT and DAPT Risk Scores for Prescribing Valgimigli et al. JACC CI 2017;10:

33 Precise DAPT Score Predicts TIMI Bleeding major or minor major Hemoglobin HR (95% CI) p 0.67 (0.53, 0.84) p = WBC 1.06 (0.99, 1.13) p = Age CrCl Prior Bleed 1.34 (1.11, 1.48) p = (0.82, 0.99) p = (1.22, 14.02) p = Costa, et al. Lancet. 2017; 389:

34 Absolute Risk Difference of Long (12-24 mos) vs. Short (3-6 mos) DAPT Duration : Ischemic*and Bleeding**Events # * *MI, def ST, CVA, TVR **TIMI Major or Minor * favors 3-6 vs mos Costa, et al. Lancet. 2017; 389:

35 Elements of Clinical Prediction Score and Distribution of Score Among Randomized DAPT Study Patients* * Derivation cohort (n=11,648) Yeh R, et al. JAMA. 2016;315(16):

36 Low DAPT score (< 2) predicts bleeding risk without ischemic benefit MI/Stent Thrombosis Moderate/Severe Bleeding Yeh R, et al. JAMA. 2016;315(16):

37 High DAPT score ( 2) predicts ischemic benefit without bleeding risk MI/Stent Thrombosis Moderate/Severe Bleeding Yeh R, et al. JAMA. 2016;315(16):

38 Risk-Benefit Assessment of a DAPT Risk Score-Guided Strategy From 6 to 24 Months: PRODIGY Subgroup Risk Difference (95% CI), % P Value for Interaction (-5.04 to 0.95) 2.91 (-0.43 to 6.25) ( to -2.25) 7.15 (-3.43 to 17.73) (-2.41 to 4.86) 2.38 (-1.12 to 5.87) 0.65 Primary Efficacy Endpoint Overall (n = 1970) High DAPT Score Low DAPT Score Paclitaxel-eluting stents (n=490) High DAPT Score Low DAPT Score Other coronary stents (n = 1480) High DAPT Score Low DAPT Score Favors 24-mo DAPT Favors 6-mo DAPT Primary Safety Endpoint Overall (n = 1970) High DAPT Score Low DAPT Score Paclitaxel-eluting stents (n=490) High DAPT Score Low DAPT Score Other coronary stents (n = 1480) High DAPT Score Low DAPT Score 0.20 (-1.20 to 1.60) 2.58 (0.71 to 4.46) (-3.27 to 2.77) 6.68 (-0.36 to 13.72) (-0.91 to 1.72) 2.00 (0.11 to 3.89) Favors 24-mo DAPT Favors 6-mo DAPT Piccolo et al. Annals of Internal Medicine 2017;167:17-25

39 DAPT Duration after Stenting: Conclusions 1. Class 1 LOE A for a BMS DAPT duration shorter than 2GDES is not evidence based 2. BMS have higher ST rates than 2G-DES and worse outcomes if DAPT is interupted/ discontinued beyond 1-3 months after PCI 3. 2G and 3G (BP-DES) derive less absolute net benefit from longer duration DAPT 4. PRECISE DAPT Score predicts short term (<1 year) risk/benefit and DAPT Score provides longer term (>1 year) risk appropriate prescription of DAPT duration for individual patients that compliments clinical variables such as MI history

40 2016 ACC/AHA Guideline Focused Update on DAPT Duration: Patients With SIHD Treated on Dual Antiplatelet Therapy COR IIb I I I I IIA IIA LOE AA B-RSR B-RSR B-NR ASR ASR Recommendations Inpatients patients withafter SIHD, BMS implantation may be In with SIHD BMS implantation, P2Y12 inhibitor therapy with clopidogrel should be givenclinical for a minimum of 1 month. considered in limited scenarios. In patients with SIHD after DES implantation, P2Y12 inhibitor therapy with clopidogrel should be given for at least 6 months. In patients with SIHD after DES* implantation, P2Y12 inhibitor therapy withtheclopidogrel should beaspirin given In patients treated with DAPT, recommended daily dose of is 81for mg to 100 mg). at (range, least 753mg months. In patients with SIHD after BMS or DES implantation who have tolerated DAPT without a bleeding complication and who are not at high bleeding In patients with SIHD after DES implantation who have risk (e.g., prior bleeding on DAPT, coagulopathy, oral anticoagulant use), continuation DAPT with toleratedofdapt without a bleeding complication and clopidogrel for longer than 1 month (BMS) or longer than 6 months (DES) who are not at high bleeding risk (e.g., prior bleeding on may be reasonable. DAPT, coagulopathy, oral anticoagulant use), continuation of DAPT with clopidogrel for longer than 3 months (DES) In may patients be with recommended.** SIHD after DES implantation who IIb * 2G/3G DES (epub) C-LD develop high risk of bleeding (e.g., treatment with oral anticoagulant therapy), are at high risk of severe bleeding complication (e.g., major intracranial surgery), or develop significant overt bleeding, discontinuation of P2Y12 inhibitor therapy after 3 months may be reasonable. ** DAPT Score 2 or greater/ PRECISE DAPT < 25 Levine, Bates, Bittle, et al. JACC 2016

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42 MACE* Following Non-Cardiac Surgery After Coronary Stenting ** ** *Death, MI, revasc; **AOR 0.75 [0.62, 0.91] DES vs. BMS Hawn et al. JAMA 2013;310: ,844 stents / 41,989 non-cardiac surgeries

43 Adverse Cardiac Events* Following Coronary Stent Placement By Stent Type And Non-Cardiac Surgery *MI or revascularization Holcomb et al. JACC 2014;64: ,590 pts stent / surgery; 41,180 pts stent only

44 Stenting Prior to Non-Cardiac Surgery : Propensity Matched Massachusetts Database - Death or MI to 30 days 8 30 day Death or MI (%) 7 DES P= P= P= P= BMS Days No. at risk Days Days Days Bangalore et al. Circ Card Int 2015;85:533

45 Cummulative Incidence of Events By Time From DES PCI to NC Surgery Comparison of patients with or without IHD having same surgery* Egholm, et. al. JACC. 2016; 68:2622 Myocardial Infarction Cardiac Death DES 1 mos Myocardial Infarction (%) Cardiac Death(%) DES 1 mos DES 1-2 DES 2-12 No IHD 1-2 No IHD 2-12 Follow-Up (Days) Patients with DES-PCI: <=1 month Patients with DES-PCI: >1-2 months Patients with DES-PCI: >2-12 months Follow-Up (Days) Patients without IHD: <= 1 month Patients without IHD: >1-2 months Patients without IHD: >2-12 months * Western Denmark Heart Registry: IHD-DES increased risk only in 1st mos post stenting (vs no-ihd)

46 LEADERS FREE in Anticoagulated Patients Primary Safety Endpoint: Cardiac Death, MI, ST* Primary Efficacy Endpoint: CI - TLR *ARC def/prob Carriè et al. JACC CI 2017;10:

47 MI Predicts Risk Early and Late Following PCI: DAPT Trial Subgroup Analysis * Any MI* No MI % *Index ( 72 hrs of PCI); History (>72 hrs prior of PCI) Kereiakes, et at. JACC 2016;67:

48 DAPT Score Utility for Risk Prediction in Patients With or Without Previous (index or Hx) Myocardial Infarction ILSD* Kereiakes et al. J Am Coll Cardiol. 2016: 67;

49 Clinical Utility of MI Status Versus DAPT Score Stratification Clinical measure MI Status NNTB for MI/ST No MI (n=6,308) NNTH for Before Stratification GUSTO Mod/Severe Bleeding Before Stratification DAPT Score group* NNTB After NNTH After DAPT score <2 (n=4,098) DAPT score 2 (n=2,210) Any MI (n=5,340) DAPT score <2 (n=1,633) DAPT score 2 (n=3,707) * Re-classify ~1/3 of patients in each MI group Stratification Stratification Kereiakes, et al. JACC 2016; 67:

50 Kaplan-Meier Curve for Composite Endpoint* at 2 Years in Patients with Previous Myocardial Infarction: ITALIC Final Results * Death, MI, TVR, stroke, major bleed Didier et al. JACC CI 2017;10:

51 Can DAPT Score predict risk of discontinuation?: Monthly MI risk difference between randomized (30 vs 12 mos) treatment arms by DAPT Score group Monthlyy MI risk diffe erence in contin nued thienop pyridine grou up vs placebo o group 0.3% No PES (n=8864) ** * 0.2% 0.1% 0.02% 0.0% -0.01% -0.01% DAPT score <2-0.1% -0.13% -0.2% -0.15% Interaction p= % DAPT score % Interaction p=0.80 Interaction p= % Months after PCI Stefanescu et al. Circulation 2017;135:

52 Randomized Trials of DAPT Duration Trials Stopped Prematurely (n=5) Bittl, et al. JACC CI 2017;10:

53 Randomized Trials of DAPT Duration Trials Achieving Preplanned Enrollment (n=9) Bittl, et al. JACC CI 2017;10:

54 Random Effects Meta-Analysis of MACCE During the First 90 Days After DAPT Discontinuation Stratified by Type of Trial Piccolo, et at. JACC CI. 2017;10:

55 DAPT STEMI: Secondary Endpoints Kedhi, et al. TCT 2017