atriumfibrilleren en coronairlijden Jur ten Berg, MD, MSc, PhD, - PowerPoint PPT Presentation

Casuỉstiek antitrombotische therapie bij atriumfibrilleren en coronairlijden Jur ten Berg, MD, MSc, PhD, FESC, FACC May 2017 St Antonius ziekenhuis, Nieuwegein, The Netherlands

Disclosures • Advisory/consulting/speakers fees : AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, Accumetrics, Boehringer Ingelheim, BMS, Pfizer, Bayer, Ferrer • Research grants : ZonMw, AstraZeneca • RE-DUAL study : executive scientific committee

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Why change duration of DAPT after ACS and PCI? Longer: Shorter: • Event rate after standard 1 year DAPT • One year DAPT after ACS based on remains high CURE and CURE-PCI with predominantly conservative treatment and when stented mostly BMS or 1st generation DES • 2nd generation DES safer (less ST) • Stronger more effective P2Y12 inhibitors while ischemic risk diminishes over time • More patients at high risk for bleedings (elderly, OAC) 5

Shorter : 2nd generation DES safer 5 Crude rates (unadjusted) Xience exp. N=13,266 ST 0.86% with different duration of FU All stents implanted 2007 – August 24 2016 8 Resolute I. N=6,687 ST 0.85% Orsiro N=7,644 ST 0.59% 3 Promus P N=24,831 ST 0.51% 2 Ultimaster N=2,266 ST 0.49% Onyx N=18,709 ST 0.39% 1 Synergy N=14,979 ST 0.26% 0 0 1 2 3 4 5 SCAAR S.James 6

Longer : HELICON study 1-year event-free MI survivors (n=76,687) Cumulative 3 year incidence of CV death, MI or stroke (%) 20 ~1 in 5 patients, % Event-free for 1 year post-MI, will suffer an MI, stroke or CV death within 3 years CV, cardiovascular; MI, myocardial infarction. Jernberg, T. et al. Eur Heart J 2015: doi:10.1093/eurheartj/ehu505 7

Casus I • Man 50 jaar, hypercholesterolemie, rookte tot electieve PCI van mid-LAD met 2 e generatie DES (3.0x15) 11-1- 2018 a)P2Y12 remmer 6 maanden b)P2Y12 remmer 12 maanden c) P2Y12 remmer > 12 maanden 8

Shorter DAPT (≤ 6 M) Most stable CAD, most 2nd generation DES, all non-inferiority design 2 nd gen Design ACS Trial N Primary Endpoint Mean Study DAPT, mth % age DES Outcome 6 vs 12 40 ISAR-SAFE 4,000 Composite of death, MI, stroke, ST, or TIMI major bleeding at 15 67 72 NI months after PCI 6 vs 12 24 ITALIC 1,822 Composite of death, MI, repeat TVR, stroke or TIMI major bleeding at 62 NI 100 12 months after PCI 6 vs 12 38 SECURITY 1,399 Composite of cardiac death, MI, stroke, ST, or BARC 3 or 5 bleeding at 65 NI 100 12 months after PCI 3 vs 12 32 OPTIMIZE 3,119 Composite of death, MI, stroke, or major bleeding at 12 months after 61 100 NI PCI 6 vs 24 75 PRODIGY 1,970 Composite of death, MI, or cerebrovascular accidents at 24 months 68 50 NI after PCI 3 vs 12 55 RESET 2,117 Composite of cardiac death, MI, ST, ischemia-driven TVR, or bleeding 62 85 NI at 12 months after PCI 6 vs 12 51 EXCELLENT 1,433 Composite of cardiac death, MI, or TVR at 12 months after PCI 63 NI 75 BARC, Bleeding Academic Research Consortium; EXCELLENT, Efficacy of Xience/Promos versus Cypher to reduce late loss after stenting; ISAR-SAFE, Randomized, double-blind, placebo-controlled trial of 6 vs 12 months clopidogrel therapy after implantation of a drug-eluting stent; ITALIC, Is there a life for DES after discontinuation of clopidogrel; OPTIMIZE, Optimized duration of clopidogrel therapy following treatment with the Endeavor Zotarolimus-eluting stent in the real world clinical practice; PRODIGY, Prolonging DAPT in patients with coronary artery disease after graded stent-induces intimal hyperplasia; RESET, A new strategy regarding discontinuation of dual antiplatelet/ real safety and efficacy of a 3-month DAPT following zotarolimus-eluting stents implantation; SECURITY, Second-generation drug-eluting stent implantation followed by 6- vs 12 month DAPT, MI myocardial infarction; NI, non-inferior; 9 ST, stent thrombosis; TIMI, Thrombolysis in Myocardial Infarction; TVR, target vessel revascularization; PCI, percutaneous coronary intervention. Montalescot et al. J Am Coll Cardiol 2015;66:832-47

Myocardial infarction: 3-6 months vs 12 months Meta-analysis for the 2016 ACC/AHA guideline focused update Prolonged Short Trial Events Events OR 95% CI 7 / 722 EXCELLENT (6 vs 12 mo) 721 13 / 0.53 (0.21-1.35) 4 / 1059 2.01 RESET (3 vs 12 mo) 1058 2 / (0.37-11.0) 42 / 1563 0.86 OPTIMIZE (6 vs 12 mo) 1556 49 / (0.56-1.30) 15 / 682 SECURITY (6 vs 12 mo) 717 16 / 0.89 (0.44-1.81) 14 / 1997 ISAR-SAFE (6 vs 12 mo) 2003 13 / 1.07 (0.50-2.29) Bayesian hierarchical meta analysis 0.90 (0.60-1.30) 82 / 6023 0.87 Fixed effect model 6055 93 / (0.65-1.18) Random effect model 0.87 (0.65-1.18) 0.2 5 10 Short better Prolonged better 0.1 0.5 1 2 Circulation. 2016;134:e156 – e178. 10

Major hemorrhage: 3-6 months vs 12 months Meta-analysis for the 2016 ACC/AHA guideline focused update Prolonged Short Trial 95% CI Events Events OR EXCELLENT (6 vs 12 mo) 721 (0.37-11.0) 4 / 2 / 722 2.01 RESET (3 vs 12 mo) 1058 (0.61-15.0) 3.01 6 / 2 / 1059 OPTIMIZE (6 vs 12 mo) 1556 (0.62-3.18) 1.41 14 / 10 / 1563 SECURITY (6 vs 12 mo) 717 (0.57-6.38) 8 / 4 / 682 1.91 ISAR-SAFE (6 vs 12 mo) 2003 (0.33-4.65) 5 / 4 / 1997 1.25 Bayesian hierarchical meta analysis (0.89-2.90) 1.67 Fixed effect model 6055 (0.99-2.84) 1.67 37 / 22 / 6023 Random effect model (0.97-2.82) 1.65 Prolonged better 0.5 10 0.1 0.2 1 2 5 Short better Circulation. 2016;134:e156 – e178. 11

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Casus II • Man 55 jaar, DM II, hypertensie met GFR = 48 ml/min, rookt nog • 2017- 1 pPCI RCA voor OWI start asa+ticagrelor (2x90 mg) • 2017- 1 PCI DES proximale LAD, PCI Cx en diffuus RCA • 2018- 1 geen AP, geen bloeding a) P2Y12 remmer (ticagrelor) had al gestopt moeten zijn b) Nog jaren continueren 13

DAPT trial, Not-Stent Thrombosis Myocardial Infarction % 10 95% CI HR P value n 12 months 8 0,45 – 0,78 0,59 <0,001 9.961 30 months 6 55% of the MI 2,9 benefit is NOT 4 related to stent thrombosis 1,8 0 18 21 24 27 0 12 15 30 33 Maanden na randomisatie 14 Mauri L, et al. Am Heart J 2010;160:1035-1041.e1

age of 65 years or older, diabetes mellitus requiring medication, a second prior spontaneous myocardial infarction, multivessel coronary artery disease, or chronic renal dysfunction GFR< 60 ml/min N= 21.000

PEGASUS-TIMI 54 Bleeding Ticagrelor, 90 mg 5 Ticagrelor, 60 mg Placebo 4 <0.001 3 2.6 2.3 <0.001 NS NS NS 2 1.3 1.2 1.1 1 0.7 0.6 0.6 0.6 0.6 0.5 0.4 0.1 0.3 0.3 0 TIMI Minor Fatal bleeding TIMI Major Fatal bleeding ICH or ICH 17 Bonaca MP et al. Am Heart J 2014; 167:437-44

Prolonged DAPT post AMI ASA only Extended DAPT Rel. Events/Total weight HR 95% CI Events/Total 2006 CHARISMA MI cohort 1943 21.4% 125 1903 162 0.77 (0.61-0.98) 2012 PRODIGY 733 13.3% 63 732 69 0.91 (0.65-1.28) 2014 ARCTIC interruption 167 1.0% 3 156 4 0.79 (0.18-3.51) 2014 DAPT 1771 14.6% 0.52 59 1805 108 (0.38-0.72) 2015 DES-LATE 1551 12.9% 56 1512 66 0.85 (0.60-1.21) 2015 PEGASUS-TIMI 54 7067 36.8% 980 14095 578 0.84 (0.76-0.94) 1 0.5 5 2 0.2 Major adverse cardiovascular events 0.78 (0.67-0.90) Cardiovascular death 0.65 (0.74-0.98) Absolute 0.3% Myocardial infarction 0.70 (0.55-0.88) Stroke 0.81 (0.68-0.97) Stent thrombosis (definite, probable) 0.50 (0.28-0.89) Major bleeding 1.73 (1.19-2.50) Non-cardiovascular death 1.03 (0.86-1.23) All-cause death 0.92 (0.83-1.03) 0.5 2.5 1 18 Udell, prolonged DAPT post AMI. Meta analysis EHJ 2016

Casus II • Man 55 jaar, DM II, hypertensie met GFR = 48 ml/min, rookt nog • 2017- 1 pPCI RCA voor OWI start asa+ticagrelor (2x90 mg) • 2017- 1 PCI DES proximale LAD, PCI Cx en diffuus RCA • 2018- 1 geen AP, geen bloeding a) P2Y12 remmer (ticagrelor) had al gestopt moeten zijn b) Nog jaren continueren PEGASUS: age of 65 years or older, diabetes mellitus requiring medication, a second prior spontaneous myocardial infarction, multivessel coronary artery disease, or chronic renal dysfunction GFR < 60 ml per minute. DAPT: no event first year, score 3 (DM, prior MI or PCI, smoking) 19

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Hart Beter

Patient: Jan Patient history Medical history • Hypertension (2002) • Type 2 diabetes mellitus (2003) • Peripheral artery disease • Renal impairment (GFR = 45 mL/min) • TIA (2011) • Paroxysmal NVAF (diagnosed 2011; CHA 2 DS 2 -VASc: 7) Personal information • Medications Beta blocker • Sex Male Statin • ACE inhibitor Age 85 years • Antidiabetics Blood pressure 161/89 mmHg • NOAC since 2013 (because of labile INR/low TTR) Pulse 69 bpm • Presentation Heavy chest pain (40 min, previous night) • Oxygen saturation 97% Pain-free at presentation

Q What is the optimal antithrombotic regimen after stenting? 1. Dual 2. Triple therapy