atriumfibrilleren en coronairlijden Jur ten Berg, MD, MSc, PhD, - - PowerPoint PPT Presentation
Casuistiek 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,
Jur ten Berg, MD, MSc, PhD, FESC, FACC
St Antonius ziekenhuis, Nieuwegein, The Netherlands May 2017
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Shorter:
CURE and CURE-PCI with predominantly conservative treatment and when stented mostly BMS or 1st generation DES
inhibitors while ischemic risk diminishes
(elderly, OAC)
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Longer:
remains high
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SCAAR S.James
1 2 3 8 5 1 2 5 3 4 Crude rates (unadjusted) with different duration of FU
All stents implanted 2007 – August 24 2016
Xience exp. N=13,266 ST 0.86% Resolute I. N=6,687 ST 0.85% Orsiro N=7,644 ST 0.59% Promus P N=24,831 ST 0.51% Ultimaster N=2,266 ST 0.49% Onyx N=18,709 ST 0.39% Synergy N=14,979 ST 0.26%
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CV, cardiovascular; MI, myocardial infarction. Jernberg, T. et al. Eur Heart J 2015: doi:10.1093/eurheartj/ehu505
Cumulative 3 year incidence of CV death, MI or stroke (%)
Event-free for 1 year post-MI, will suffer an MI, stroke or CV death within 3 years
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a)P2Y12 remmer 6 maanden b)P2Y12 remmer 12 maanden c) P2Y12 remmer > 12 maanden
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Trial ISAR-SAFE ITALIC SECURITY OPTIMIZE PRODIGY RESET EXCELLENT N 4,000 1,822 1,399 3,119 1,970 2,117 1,433 Design 6 vs 12 6 vs 12 6 vs 12 3 vs 12 6 vs 24 3 vs 12 6 vs 12 Primary Endpoint Composite of death, MI, stroke, ST, or TIMI major bleeding at 15 months after PCI Composite of death, MI, repeat TVR, stroke or TIMI major bleeding at 12 months after PCI Composite of cardiac death, MI, stroke, ST, or BARC 3 or 5 bleeding at 12 months after PCI Composite of death, MI, stroke, or major bleeding at 12 months after PCI Composite of death, MI, or cerebrovascular accidents at 24 months after PCI Composite of cardiac death, MI, ST, ischemia-driven TVR, or bleeding at 12 months after PCI Composite of cardiac death, MI, or TVR at 12 months after PCI Mean 67 62 65 61 68 62 63 age ACS 40 24 38 32 75 55 51 % 2nd gen 72 100 100 100 50 85 75 DES 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; 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 Study NI NI NI NI NI NI NI Outcome DAPT, mth
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Trial EXCELLENT (6 vs 12 mo) RESET (3 vs 12 mo) OPTIMIZE (6 vs 12 mo) SECURITY (6 vs 12 mo) ISAR-SAFE (6 vs 12 mo) Bayesian hierarchical meta analysis Fixed effect model Random effect model Events 7 / 4 / 42 / 15 / 14 / 82 / 721 1058 1556 717 2003 6055 Events 13 / 2 / 49 / 16 / 13 / 93 / 722 1059 1563 682 1997 6023 OR 0.53 2.01 0.86 0.89 1.07 0.90 0.87 0.87 95% CI (0.21-1.35) (0.37-11.0) (0.56-1.30) (0.44-1.81) (0.50-2.29) (0.60-1.30) (0.65-1.18) (0.65-1.18) 0.1 0.2 0.5 1 2 5 10 Prolonged Short Short better Prolonged better
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Trial EXCELLENT (6 vs 12 mo) RESET (3 vs 12 mo) OPTIMIZE (6 vs 12 mo) SECURITY (6 vs 12 mo) ISAR-SAFE (6 vs 12 mo) Bayesian hierarchical meta analysis Fixed effect model Random effect model Events 4 / 6 / 14 / 8 / 5 / 37 / 721 1058 1556 717 2003 6055 Events 2 / 2 / 10 / 4 / 4 / 22 / 722 1059 1563 682 1997 6023 OR 2.01 3.01 1.41 1.91 1.25 1.67 1.67 1.65 95% CI (0.37-11.0) (0.61-15.0) (0.62-3.18) (0.57-6.38) (0.33-4.65) (0.89-2.90) (0.99-2.84) (0.97-2.82) 0.1 0.2 0.5 1 2 5 10 Prolonged Short Short better Prolonged better
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a) P2Y12 remmer (ticagrelor) had al gestopt moeten zijn b) Nog jaren continueren
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DAPT trial, Not-Stent Thrombosis Myocardial Infarction
Maanden na randomisatie 12 15 18 21 30 33 % 10 8 6 24 27 4
HR 0,59 95% CI 0,45 – 0,78 P value <0,001 n 9.961 12 months 30 months
1,8 2,9 55% of the MI benefit is NOT related to stent thrombosis
Mauri L, et al. Am Heart J 2010;160:1035-1041.e1
N= 21.000
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
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Bonaca MP et al. Am Heart J 2014; 167:437-44
1 2 3 4 TIMI Major 5 TIMI Minor Fatal bleeding ICH Fatal bleeding
2.6 2.3 1.1 1.3 1.2 0.4 0.6 0.6 0.7 0.6 0.6 0.5 0.1 0.3 0.3 <0.001 <0.001 NS NS NS
Ticagrelor, 90 mg Ticagrelor, 60 mg Placebo
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Udell, prolonged DAPT post AMI. Meta analysis EHJ 2016
2006 CHARISMA MI cohort 2012 PRODIGY 2014 ARCTIC interruption 2014 DAPT 2015 DES-LATE 2015 PEGASUS-TIMI 54 125 63 3 59 56 980 1903 732 156 1805 1512 14095 162 69 4 108 66 578 1943 733 167 1771 1551 7067 21.4% 13.3% 1.0% 14.6% 12.9% 36.8% 0.77 0.91 0.79 0.52 0.85 0.84 (0.61-0.98) (0.65-1.28) (0.18-3.51) (0.38-0.72) (0.60-1.21) (0.76-0.94) Major adverse cardiovascular events Cardiovascular death Myocardial infarction Stroke Stent thrombosis (definite, probable) Major bleeding Non-cardiovascular death All-cause death 0.78 0.65 0.70 0.81 0.50 1.73 1.03 0.92 (0.67-0.90) (0.74-0.98) (0.55-0.88) (0.68-0.97) (0.28-0.89) (1.19-2.50) (0.86-1.23) (0.83-1.03) 0.2 0.5 1 2 5 0.5 1 2.5 Extended DAPT Events/Total ASA only Events/Total Rel. weight HR 95% CI
Absolute 0.3%
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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)
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Personal information Sex Male Age 85 years Blood pressure 161/89 mmHg Pulse 69 bpm Oxygen saturation 97%
Patient: Jan
Patient history Medical history
Medications
Presentation
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Randomization ≤120 hours post-PCI* 6-month minimum treatment duration with visits every 3 months for the first year, then visits and telephone contact alternating every 3 months and a 1-month post-treatment visit
Patients with AF undergoing succesful PCI with stenting no recent < 1 m ICH, stroke, surgery, bleeding CrCl <30mL/min Dabigatran 150 mg BID + P2Y12 inhibitor Dabigatran 110 mg BID + P2Y12 inhibitor Warfarin (INR 2.0–3.0) + P2Y12 inhibitor + ASA
Dabigatran (110 or 150 mg) Warfarin 1 month of ASA (BMS) 3 months of ASA (DES)
N=2725 Mean duration of follow-up: ~14 months
P2Y12 inhibitor P2Y12 inhibitor
» Full analysis set presented. HRs and Wald CIs from Cox proportional-hazard model. For the dabigatran 110 mg vs warfarin comparison, the model is stratified by age, non-elderly vs elderly (<70 or ≥70 in Japan and <80 or ≥80 years old elsewhere). For the dabigatran 150 mg vs warfarin comparison, an unstratified model is used, elderly patients outside the USA are excluded. Non- inferiority P value is one sided (alpha=0.025). Wald two-sided P value from (stratified) Cox proportional-hazard model (alpha=0.05)
Probability of event (%)
90 180 270 360 450 540 630 720 Time to first event (days) 40 35 30 25 20 15 10 5
Warfarin triple therapy Dabigatran 110 mg dual therapy
HR: 0.52 (95% CI: 0.42–0.63) Non-inferiority P<0.0001 P<0.0001
90 180 270 360 450 540 630 720 Time to first event (days) 40 35 30 25 20 15 10 5
Dabigatran 150 mg dual therapy Warfarin triple therapy
HR: 0.72 (95% CI: 0.58–0.88) Non-inferiority P<0.0001 P=0.002
» Non-inferiority P value is one sided (alpha=0.025). Results presented are Step 3 of hierarchical testing procedure, testing non-inferiority of dabigatran dual therapy (combined doses) to warfarin triple therapy in death or thromboembolic event and unplanned revascularization
35 30 25 20 15 10 5 Probability of event (%) 90 180 270 360 450 540 630 720 Time to first event (days) Dabigatran (combined doses) dual therapy Warfarin triple therapy