32ste WCN Congres 28-29 november 2019 CHANGE in anticoagulation and antithrombotic therapy Marco Alings
(potentiele) belangenverstrengeling Onderzoeksgeld, honorarium of andere Bayer, Boehringer Ingelheim, Bristol- (financiële) vergoeding Myers Squibb, Daiichi Sankyo, Milestone, Pfizer, Roche Diagnostics, Sanofi National coördinator COMPASS Marco Alings 28-11-2019
CHANGE in anticoagulation and antithrombotic therapy Long term intensive anti-thrombotic treatment: 1. DPI: antiplatelet plus anticoagulant of 2. DAPT: dual antiplatelet
APT DAPT DPI Welsh et al., Am Heart J 2019;218:100-109
Inhoud • de casus • Dual pathway inhibition (DPI): wat is het? En bij wie? • Take home messages Marco Alings 28-11-2019
Casus Recent zag ik de 69 jr mevrouw L. terug op de poli. Een jaar geleden maakte zij een voorwand infarct door waarvoor DES mid-LAD. Redelijke LVF. Zij is nu cardiaal stabiel, heeft geen angineuze klachten, maar loopafstand is beperkt. Lab: LDL-C 1.9 mMol/l VG/ ü 2018 AMI voorwand, DES LAD; LVEF 40%. ü overig: Fontaine IIA (looptherapie), DMII(?), Hypertensie ü R/ ticagrelor 90 mg 2dd1, Ascal 80 mg 1dd1 , bisoprolol 5 mg 1dd1, perindopril 4 mg 1dd1, spironolacton 25 mg 1dd1, atorvastatine 40 mg 1dd1 Marco Alings 28-11-2019
Een jaar na stenting kan DAPT worden gestaakt en volstaat verdere antithrombotische behandeling met alleen aspirine (naast betablokker, ACE-remmer, LDL- en bloeddrukmanagement en controle [glc]) NO YES Marco Alings 28-11-2019
Wie continueert na een jaar de behandeling met (een vorm van) DAPT? (bv ASA + clopidogrel, ASA + ticagrelor 60/90 mg) ik niet ik Marco Alings 28-11-2019
Wie stopt DAPT en start behandeling met DPI? ik niet Huh? Vertel eerst maar ik eens wat meer over DPI Marco Alings 28-11-2019
Secondary prevention in cardiovascular trials Lipid lowering BP Lowering ACE Aspirin 5 Outcome (1 mmol/L) 1,2 (10 mm Hg) (HOPE) 3 4 18% 22% 21% 20% MACE 14.0% vs 17.8% HR 0.78; 0.69 - 0.89 HR 0.80; 0.77 - 0.83 0.28% vs 0.34% HR 0.78; 0.70 - 0.86 HR 0.82; 0.75 – 0.90 Mortality 9% 13% 16% 9% Stroke 15% 27% 32% 19% MI 24% 17% 20% 20% despite secondary prevention therapies, 9 to 18% of patients with cardiovascular disease have recurrent events each year 6 Marco Alings 28-11-2019 1. Collins R, et al. Lancet 2016;388:2532-61; 2. CTT Collaboration. Lancet 2015;385:1397-1405; 3. Ettehad D, et al. Lancet 2016;387:957-67; 4. Yusuf S, et al. N Engl J Med 2000;342:145-53; 5. ATT Collaboration. Lancet 2009;373:1849-60; 6. Bhat et al, JAMA 2010; 304: 1350-7
lipids inflammation Vascular protection anticoagulation Marco Alings 28-11-2019 N Engl J Med 2017;377:1119-31
anticoagulation in patients with CAD DPI 1. Adapted from Angiolillo DJ et al. Eur Heart J 2010;31:17–28; 2. Croce K and Libby P. Curr Opin Hematol 2007;14:55–61; 3. Siller-Matula et al. Thromb Haemost 2011;106: 1020–1033; 4. Adapted from Mitchell JR. Marco Alings 28-11-2019 BMJ 1981;282:590–594.
Alternative to aspirin: VKA’s Meta-analysis, 20,000 patients: Vit K antagonist (INR >2.8) significantly reduced MACE (HR • 0.58) but increased bleeding (including ICH) (HR 4.5) bleeding MACE HR 4.5 (3.5-6.0) HR 0.58 (0.52-0.64) Marco Alings 28-11-2019 Anand SS, J Am Coll Cardiol 2003; 41: Suppl S: 62S - 69S
ATLAS-TIMI 51 • 15,526 patients with a recent ACS à rivaroxaban 2.5 mg or 5 mg 2dd or placebo Major bleed (not CABG related): • • Primary: MACE: – 10.7% � 8.9% (HR 0.84; 0.74 - 0.96); p = 0.008 – 0.6% � 2.1% (HR 3.96; 2.46-6.38) 2.5-mg dose: 9.1% vs 10.7%, p = 0.02 – fatal bleeding: 0.3% vs. 0.2%, p = 0.66 – 5-mg dose 8.8% vs. 10.7%, p = 0.03 – 10.7% 8.9% Marco Alings 28-11-2019 N Engl J Med 2012;366:9-19
COMPASS Hypothesis : is rivaroxaban alone or combination of riva + aspirin more • effective than aspirin alone in preventing recurrent cardiovascular events, with acceptable safety, in patients with stable atherosclerotic vascular disease Primary endpoint : CV death, stroke, myocardial infarction • Secondary endpoint : CHD death, i-stroke, MI, acute limb ischemia • Safety outcome : major bleeding (modified ISTH); fatal bleeding; symptomatic • bleeding into critical organ; bleeding leading to hospitalization (including ER visit) Marco Alings 28-11-2019 Eikelboom et al., New Engl J Med 2017;377(14):1319-1330
COMPASS Rivaroxaban 2.5 mg bid + Aspirin 100 mg od Rivaroxaban 5 mg bid R Run-in Aspirin 100 mg od (Aspirin) Expected mean follow up: 3-4 years R Pantoprazol 40 mg placebo N Engl J Med 2017; 377(14):1319-1330 Marco Alings 28-11-2019 Eikelboom et al., New Engl J Med 2017;377(14):1319-1330
COMPASS n=27,395; 602 sites; 33 countries; trial prematurely stopped for efficacy after a mean follow-up 23 months Canada Netherlands N=2443 N=2522 United States N=1475 Czech Republic China N=1553 N=1086 Japan N=1556 Italy N=1018 Brazil N=1515 Argentina N=2789 Marco Alings 28-11-2019 Eikelboom et al., New Engl J Med 2017;377(14):1319-1330
COMPASS: baseline characteristics Riva 2.5 mg bid + ASA Riva 5 mg bid ASA n =9,152 n =9,117 n =9,126 Age, yr 68 68 68 Female 22% 22% 22% SBP/DBP, mmHg 136/77 136/78 136/78 Cholesterol, mmol/L 4.2 4.2 4.2 CAD 91% 90% 90% PAD 27% 27% 27% Diabetes 38% 38% 38% Lipid-lowering 90% 90% 89% ACE-I/ARB 71% 72% 71% PPI (non study) 36% 36% 36% Marco Alings 28-11-2019 Eikelboom et al., New Engl J Med 2017;377(14):1319-1330
COMPASS primary endpoint: CV death, stroke, MI Riva + ASA vs. ASA Riva vs. ASA Riva R + A Aspirin HR (95% CI) HR (95% CI) (n = 9,117) (n = 9,152) (n =9,126) CV death, 379 448 496 0.76 0.90 <0.0001 0.11 4.1% 4.9% 5.4% (0.66-0.86) (0.79-1.03) stroke, MI R+A vs A: HR 0.76 (0.66-0.86) 0.10 R vs A: HR 0.90 (0.79-1.03) Aspirin 0.08 Rivaroxaban + Aspirin vs. Aspirin HR: 0.76 (0.66-0.86) P=<0.0001 Rivaroxaban Rivaroxaban vs. Aspirin HR: 0.90 (0.79-1.03) P= 0.115 Cumulative Hazard Rate Rivaroxaban + Aspirin 0.06 0.04 0.02 Mean follow up 23 months (maximum 47 months) 0.0 0 1 2 3 Marco Alings 28-11-2019 isk N Engl J Med. 2017;377(14):1319-1330 Eikelboom et al., New Engl J Med 2017;377(14):1319-1330
COMPASS components primary endpoint Riva + ASA vs. ASA R + A Aspirin HR (95% CI) (n = 9,152) (n =9,126) 160 203 0.78 CV death <0.02 1.7% 2.2% (0.64-0.96) 83 142 0.58 stroke <0.0001 0.9% 1.6% (0.44-0.76) 64 125 0.51 ischemic <0.0001 0.7% 1.4% (0.38-0.69) 5 14 0.35 hemorrhagic 0.04 <0.1% <0.1% (0.13-0.99) 178 205 0.86 MI 0.14 1.9% 2.2% (0.70-1.05) Marco Alings 28-11-2019 Eikelboom et al., New Engl J Med 2017;377(14):1319-1330
COMPASS major bleed Riva + ASA vs. ASA Riva vs. ASA Riva R + A Aspirin HR (95% CI) HR (95% CI) (n = 9,117) (n = 9,152) (n =9,126) 288 252 170 1.70 1.51 Major bleed <0.0001 <0.0001 3.1% 2.8% 1.9% (1.40-2.05) (1.25-1.84) 0.10 R+A vs A: HR 1.70 (1.40-2.05) 0.08 Cumulative Hazard Rate R vs A: HR 1.51 (1.25-1.84) Rivaroxaban + Aspirin vs. Aspirin HR: 1.70 (1.40-2.05) P=<0.0001 0.06 Rivaroxaban vs. Aspirin HR: 1.51 (1.25-1.84) P=<0.0001 Rivaroxaban + Aspirin 0.04 Rivaroxaban Aspirin 0.02 Mean follow up 23 months (maximum 47 months) 0.0 0 1 2 3 Marco Alings 28-11-2019 isk Eikelboom et al., New Engl J Med 2017;377(14):1319-1330 N Engl J Med. 2017;377(14):1319-1330 24
COMPASS components major bleeds Riva + ASA vs. ASA R + A Aspirin HR (95% CI) (n = 9,152) (n =9,126) 288 170 0.78 Major bleed p <0.02 (3.1%) (1.9%) (0.64-0.96) 15 10 1.49 fatal p=0.32 (0.2%) (0.1%) (0.67-3.33) 21 19 1.101 Non fatal ICH p=0.77 (0.2%) (0.2%) (0.59-2.04) 42 29 1.43 Critical site p=0.14 (0.5%) (0.3%) (0.89-2.29) 210 112 1.88 other p<0.0001 (2.3%0 (1.2%) (1.49-2.36) 140 65 2.15 GI bleed <0.0001 (1.5%) (0.7%) (1.60-2.89) Marco Alings 28-11-2019 Eikelboom et al., New Engl J Med 2017;377(14):1319-1330
COMPASS: major bleeds excluding serious bleeds requiring a two unit transfusion or with a hemoglobin drop of at least 2g/dL) 0.10 Major bleed, not fatal or in critical organ or requiring two units transfusion 0.08 Cumulative Hazard Rate 0.06 Rivaroxaban + Aspirin vs. Aspirin HR: 1.56 (1.18-2.06) P=0.002 Rivaroxaban vs. Aspirin HR: 1.34 (1.01-1.79) P=0.045 0.04 0.02 Rivaroxaban + Aspirin Rivaroxaban Aspirin 0.0 0 1 2 3 isk aban + Aspirin 9152 7941 3938 661 Marco Alings 28-11-2019 Eikelboom et al., New Engl J Med 2017;377(14):1319-1330
COMPASS net clinical benefit Composite NCB outcome of: • Cardiovascular death, stroke, myocardial infarction, fatal bleeding, or symptomatic bleeding into a critical organ Riva + ASA vs. ASA R + A Aspirin HR (95% CI) (n = 9,152) (n =9,126) Net clinical 431 534 0.80 <0.001 benefit 4.7% 5.8% (0.70-0.91) Marco Alings 28-11-2019 Eikelboom et al., New Engl J Med 2017;377(14):1319-1330
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