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Discussant review:
- CANTOS -
Discussant review: - CANTOS - The Canakinumab Anti-Inflammatory - - PowerPoint PPT Presentation
Discussant review: - CANTOS - The Canakinumab Anti-Inflammatory - - PowerPoint PPT Presentation
Discussant review: - CANTOS - The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study Malte Kelm, MD Professor and Chairman Department of Cardiology, Pulmology and Vascular Medicine University Hospital Dsseldorf CANTOS: C anakinumab An
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- Chronic inflammation in atherosclerosis
- Patient (and target) population
- Effect size, tailoring therapy
- Non-cardiovascular effects and safety
CANTOS: Canakinumab Anti-Inflammatory Thrombosis Outcomes Study
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N Engl J Med 1997;336:973-979
effect size stability
hsCRP reflects inflammation in humans
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N Engl J Med 1997;336:973-979
IL6 upstream signalling independent risk indication effect size stability
- Lancet. 2010;375:132-140
Eur Heart J. 2014;35:578-89
hsCRP reflects inflammation in humans
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Activation of inflammasome - “clinical utility”
Circ Res. 2016;118:145-156 & Ischemia
NLRP3
inflammasome
IL-1β TNF IL-6 hsCRP target converter distributor biomarker
Canakinumab
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Cholesterol crystals induce local and systemic inflammation
experimental studies
monocytes & macrophages volume expansion intima perforation
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Cholesterol crystals induce local and systemic inflammation
experimental studies
monocytes & macrophages volume expansion intima perforation
human studies
Carotid artery coronary artery systemic effects
Eur Heart J. 2016;37:1959-67,
- Science. 2015;349:237-8,
- Circ. Res. 2017;120:1947-57
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Additional LDL Reduction IMPROVE-IT : Ezetimibe 6% RRR FOURIER/SPIRE: PCSK9 Inhibition q2 weeks 15% RRR Known Cardiovascular Disease LDL 150 mg/dL hsCRP 4.5mg/L Additional Inflammation Reduction CANTOS: Proof of Concept High Intensity Statin LDL 80 mg/dL hsCRP 3.8 mg/L LDL 110 mg/dL hsCRP 1.8 mg/L
“Residual Cholesterol Risk” “Residual Inflammatory Risk”
Residual risk in HR-patients with CAD: >50%
Eur Heart J 2016;37:1720-22
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CANTOS - baseline clinical characteristics
Ridker ESC 2017 N Engl J Med 2011;364:226-35
PROSPECT - event rate post pPCI / AMI
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Ridker ESC 2017
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Tailored therapy in CAD
Additional LDL Reduction Known Cardiovascular Disease LDL 150 mg/dL hsCRP 4.5mg/L Additional Inflammation Reduction High Intensity Statin LDL low hsCRP high LDL high hsCRP low
“Residual Cholesterol Risk” “Residual Inflammatory Risk” “Residual Thrombotic Risk”
HTPR Additional antiplatelet & anticoagulant therapy
?
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IL-1β in sterile inflammation and non-CVD
Nat Rev Drug Discov; 2012,11: 633-652
Canakinumab
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CRP & (non) cardiovascular mortality
Lancet 2010; 375: 132-40
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Ridker ESC 2017
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- supports the concept of causal anti-inflammatory therapy in
atherosclerosis
- ffers the perspective of tailored indication, treatment & monitoring
- f anti-inflammatory therapy in secondary prevention in high risk
patients
- need to proof the transition of this concept to patients with AMI
- safety has to be further evaluated in post-trial registries in