PowerPoint-Präsentation

PowerPoint-Präsentation

Peter Sinnaeve 1 NEW INSIGHTS INTO RISK ASSESSMENT & PREVENTION IN STEMI PATIENTS Peter Sinnaeve Department of Cardiovascular Medicine University Hospitals Leuven University of Leuven Belgium Peter Sinnaeve Disclaimer Please note some of the data presented herein may contain off-label dosages and use. Please always refer to the current prescribing information as approved in your country. 2 Peter Sinnaeve Disclosures Peter Sinnaeve is a Clinical Investigator for the Fund for Scientific Research Flanders Institutional grants from AstraZeneca, Bayer, Daiichi-Sankyo Advisory, consultancy, RCT, CEC and speakers fees (all institutional) from AstraZeneca, Sanofi, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, BMS, Pfizer, Abbott, Amgen, MSD, Itreas, GSK, Medtronic, Celgene, Idorsia 3

Peter Sinnaeve 4 Risk assessment & prevention opportunities in STEMI Pre-hospital ECG ST-segment Clinical presentation Catheterisation Lab TIMI flow pre/post Haemodynamics/ FFR Coronary Care Unit ECG ST resolution Biomarkers Discharge Cardiac US / MRI Risk scores After Ahmed N et al. J Comp Eff Res 2016;5(6):581-593. Peter Sinnaeve

5 Risk assessment & prevention opportunities in STEMI Pre-hospital ECG ST-segment Clinical presentation Catheterisation Lab TIMI flow pre/post Haemodynamics/ FFR Coronary Care Unit ECG ST resolution Biomarkers Discharge Cardiac US / MRI Risk scores After Ahmed N et al. J Comp Eff Res 2016;5(6):581-593. Peter Sinnaeve 6

Initial STEMI - ECG: a sophisticated yet still universal tool Baseline STDSTD Quartiles: Relative risk (95% CI)* P Value 1 0.024 Event rate: 0-9 mm (reference) 43/479 (9.0) 9.5-13.5 mm 63/467 (13.5) 1.42 (0.98-2.05) 14-19.5 mm 66/448 (14.7) 1.66 (1.16-2.38) >19.5 mm 69/456 (15.1) 1.52 (1.05-2.18) Continuous: every 5 mm increase

0.0 1.09 (1.03-1.15) 0.5 1.0 1.5 Bainey KR et al. for the STREAM Investigators. Heart 2016;102:527-533. 0.008 The sum of ST-segment deviation (or elevation) correlates with 30-day death/shock/ CHF/reMI No impact on the response to different reperfusion strategies 2.0 CHF, congestive heart failure; STD, sum of ST-segment deviation STD, sum of ST-segment deviation Peter Sinnaeve 7

But just make sure you get your ECG right Reasons for false-negative ECG interpretations (N=47) Bosson N et al. J Prehosp Em Care 2017;21(3):283-290. Reasons for false-positive ECG interpretations (N=585) *STEMI statement suppressed Peter Sinnaeve 8 Risk assessment & prevention opportunities in STEMI Pre-hospital ECG ST-segment Clinical presentation Catheterisation Lab TIMI flow pre/post Haemodynamics/ FFR Coronary Care Unit ECG ST resolution Biomarkers

Discharge Cardiac US / MRI Risk scores After Ahmed N et al. J Comp Eff Res 2016;5(6):581-593. Peter Sinnaeve 9 Mortality (%) (Simple) Risk scores in the acute phase of a STEMI? The Shock Index (SI) 25 20 Mortality in STEMI: the shock index (HR/SBP) 15 10 5 0 SI 0.26-0.51 SI 0.52-0.61

Bilkova D et al. Can J Cardiol 2011;27(6):739-742. SI 0.62-0.78 SI 0.79-2.47 ~ Killip class, btw Peter Sinnaeve 10 In -h o sp ita l M o rta lity (Simple) Risk scores in the acute phase of a STEMI? TIMI Risk Index 20% 60% 15% 50% 40% 30% 10% NS TEMI STEMI-RT STEMI-No RT 10.9% 6.6% 18.7% 5% 0%

Heart Rate x (age/10)2 Systolic Pressure Diagnosis 20% 10% Seems to reflect (pre-)shock, right? 0% -10% TIMI Risk Index Wiviott SD et al. J Am Coll Cardiol 2006;47(8):1553-1558. Peter Sinnaeve 11 Risk scores in the acute phase of a STEMI? Outside the box CHA2DS2-VASc & failed lysis 100 100 80 Sensitivity Sensitivity

80 CHA2DS2-VASc-HS & failed lysis 60 40 2 20 60 40 3 20 CHA2DS2-VASc 2 (AUC 0.660; 95% CI:0.618-0.700; p<0.001) 0 0 2 0 4 6 8 0 0 0 100-Specificity

Kilic S et al. Cardiol J 2019;26(2):169-175. 100 CHA2DS2-VASc-HS 3 (AUC 0.764; 95% CI:0.725-0.799; p<0.001) 0 0 2 0 4 6 8 0 0 0 100-Specificity 100 CHA2DS2-VASc(HS) is predictive for successful or failed reperfusion after fibrinolytic therapy Not really necessary to calculate, but shows that comorbidities predict

efficacy of lytic Rx Peter Sinnaeve 12 Risk assessment & prevention opportunities in STEMI Pre-hospital ECG ST-segment Clinical presentation Catheterisation Lab TIMI flow pre/post Haemodynamics/ FFR Coronary Care Unit ECG ST resolution Biomarkers Discharge Cardiac US / MRI Risk scores After Ahmed N et al. J Comp Eff Res 2016;5(6):581-593.

Peter Sinnaeve Time is a modifiable risk factor in STEMI My favourite STEMI risk tool is my (stop)watch 13 Peter Sinnaeve 14 How we perform in real life How do we perform ? Poorly! More than one third of STEMI patients referred to a PCI-centre for primary PCI fail to achieve a time delay of less than 120 minutes, despite estimated transfer times of <60 minutes Ibanez B et al. Eur Heart J 2018;39(2):119-177. Dauerman HL et al. Circ Cardiovasc Interv 2015;8(5):e002450. Peter Sinnaeve 15 Improved quality, yet higher mortality! 2012 Guidelines 90 minutes 60 minutes if early presenter (<2h) 2017 Guidelines 120 minutes

2012 2017 % patients Rx within guideline window 5.7% 85.8% % mortality 1.6% (95% CI: 0.42.8) 3.3% (95% CI: 2.93.7) Lapostolle F et al. Eur J Emerg Med 2019 Jan 14. doi: 10.1097/MEJ.0000000000000586. [Epub ahead of print]. Peter Sinnaeve 16 Perception time delays in PPCI really do kill patients too 1-y mortality One-year mortality, % 12 6 RCTs of Primary PCI by Zwolle Group 1994 2001 (n=1,791) 10

8 6 p <0.0001 4 2 0 0 RR=1.08 [1.01 1.16] for each 30-min delay (p=0.04) 60 120 180 240 Ischaemic Time (min) De Luca G et al. Circulation 2004;109(10):1223-1225. 300 360 Peter Sinnaeve 17 ESC ACCA Pre-hospital Management Position paper MINDSET Possible? Shouldnt that rather be (almost) guaranteed??

Primary PCI possible within 120 minutes after FMC Beygui F et al. Eur Heart J Acute Cardiovasc Care; 2015:1-23. Peter Sinnaeve 18 Beyond mortality: preventing cardiogenic shock in STEMI Meta-analysis: pharmacoinvasive strategy vs PPCI on the incidence of cardiogenic shock Pharmacoinva PPCI sive Vanhaverbeke M et al. Circulation 2019;139(1):137-139. Please note some of the data presented herein may contain off-label dosages and use. Please always refer to the current prescribing information as approved in your country. Peter Sinnaeve 19 Beyond mortality: preventing cardiogenic shock in STEMI Infarct Size Pharmacoinvas ive Vanhaverbeke M et al. Circulation 2019;139(1):137-139.

PPCI Relative Risk* (95%CI) Peter Sinnaeve 20 Beyond mortality: preventing cardiogenic shock in STEMI Meta-analysis of PPCI vs pharmacoinvasive Rx 17 studies (incl. 6 RCTs), n=13,037 Study or Subgroup 1. All-cause short-term mortality 2. Likelihood of achieving TIMI-3 flow 3. Total stroke 4. Haemorrhagic Stroke 5. Ischaemic stroke 6. Cardiogenic shock 7. Major bleeding 8. Reinfarction 9. All-cause long-term mortality Endpoints are 30-day/in-hospital Siddiqi TJ et al. Am J Cardiol 2018;122:542-547. Odds Ratio IV, Random, 95% Cl 0.99 [0.73, 1.34] 1.06 [0.70, 1.59] 0.41 [0.18, 0.93] 0.23 [0.06, 0.81] 0.49 [0.15, 1.56] 1.53 [1.08, 2.18] 0.97 [0.37, 2.54] 0.55 [0.31, 0.99]

0.83 [0,59, 1.17] Odds Ratio IV, Random, 95% Cl PPCI Pharmacoinvasive Peter Sinnaeve 21 Predicting/preventing pre-hospital sudden death in STEMI Mortality x 10 Predictors: Age Congestive Heart Failure Mortality 4.0% Mortality 37.7% Karam N et al. Circ Vasc Int 2019;12(1):e007081. doi: 10.1161/CIRCINTERVENTIONS.118.007081. Extensive MI Peter Sinnaeve 22 As important as risk for ischaemic events: avoiding bleedings Half-dose bolus TNK in elderly STEMI patients STREAM

and a radial approach @ angio Amendment Before TNK After <75y 75y <75y 75y Bolus Bolus Bolus Bolus 600 mg loading 75 mg/d No loading 75 mg/d Clopidogrel 600 mg loading 75 mg/d

Enoxaparin 30 mg bolus 1 mg/kg bid No bolus 0.75 mg/kg bid 30 mg bolus 1 mg/kg bid No bolus 0.75 mg/kg bid 156 42 653 93 12.9 31.0 9.2 24.7 5.2 19.1 2.5

11.8 1-year (%) 7.8 21.4 4.3 15.1 ICH(%) 1.3 7.1 1.2 0.0 n Primary EP (%) All-cause death 30-day (%) No loading 75 mg/d Sinnaeve PR et al. Drugs Aging 2016;33(2):109-118. ==

Please note some of the data presented herein may contain off-label dosages and use. Please always refer to the current prescribing information as approved in your country. Peter Sinnaeve 23 Risk assessment & prevention opportunities in STEMI Pre-hospital ECG ST-segment Clinical presentation Catheterisation Lab TIMI flow pre/post Haemodynamics/ FFR Coronary Care Unit ECG ST resolution Biomarkers Discharge Cardiac US / MRI Risk scores

After Ahmed N et al. J Comp Eff Res 2016;5(6):581-593. Peter Sinnaeve 24 Reperfusion before PCI lower NT-proBNP ~ mortality 8 7 TIMI Flow before PCI p=0.024 Pint=0.523 6.7 Survival Regardless of reperfusion strategy P=0.004 Pint=0.138 6.6 6.4 6.4 6.1 6 6.0 5.9 5.5 5

4 n= TIMI 0-1 160 347 TIMI 2-3 319 128 TIMI 0-1 135 288 Log BNP at Day 7/discharge TNK+PCI Datenreihe 2 PCI Sinnaeve PR et al. Eur Heart J 2009;30(18):2213-2219. TIMI 2-3 260 114 Day 90 Months since randomisation Peter Sinnaeve 25 Reperfusion before & after PCI role of thrombus TIMI Thrombus Grade & 90d death T-TIME: no benefit of low-dose lytic after PCI

Death at 90 days 40% p=0.003 30% p=0.001 20% 10% 0% TTG after PCI p=0.407 p=0.235 0 21/479 15/113 Facilitated PCI 1 15/523 11/118 Primary PCI Zalewski J et al. J Am Coll Cardiol 2011;57(19):1867-1873. McCartney PJ et al. JAMA 2019;321(1):56-68. Plus: thrombectomy doesnt work as well Peter Sinnaeve 26 Does endogenous fibrinolysis play a role? New opportunities for interventions. Point-of-care Global Thrombosis Test in STEMI pts

LT = Lysis Time Poor endogenous fibrinolysis Farag M et al. Eur Heart J 2019;40(3):295-305. Sinnaeve PR & Van de Werf F. Eur Heart J 2019;40(3):306-308. Peter Sinnaeve 27 Risk assessment & prevention opportunities in STEMI Pre-hospital ECG ST-segment Clinical presentation Catheterisation Lab TIMI flow pre/post Haemodynamics/ FFR Coronary Care Unit ECG ST resolution Biomarkers Discharge

Cardiac US / MRI Risk scores After Ahmed N et al. J Comp Eff Res 2016;5(6):581-593. Peter Sinnaeve 28 Risk indicators CHF HTN Age75 Death at 1 Year TIMI risk score in secondary prevention (TRS-2P) DM P-trend <0.001 40% 34.7% 35% 30% 25.3% 25% Prior Stroke 20%

Prior CABG 14.0% 15% PAD eGFR<60 10% Current Smoking 5% #Risk Indicators Populations (N) Populations (%) Total events (n) Puymirat E et al. Clin Cardiol 2019;42:227-234. 0% 5.7% 1.8% 2.5% 0 1 2

3940 31 100 3108 24 177 1506 12 27 3 2101 16.5 294 4 5 1231 10 311 829 7 288 Peter Sinnaeve Take home messages Risk scores can be useful in STEMI reflect comorbidities & risk of developing shock In STEMI, TIME is definitely a modifiable risk factor (and should be part of every risk assessment)

Reducing time delays in reperfusion for STEMI saves cardiac muscle & lives, and may prevent shock Paradoxically, more relaxed guidelines seem to be associated with increased mortality through longer delays In STEMI patients unable to undergo expedited PPCI, (half-dose) lytic therapy and transport to a PCI-capable centre is the preferred strategy Please note some of the data presented herein may contain off-label dosages and use. Please always refer to the current prescribing information as approved in your country. Peter Sinnaeve 30 NEW INSIGHTS INTO RISK ASSESSMENT & PREVENTION IN STEMI PATIENTS Peter Sinnaeve Department of Cardiovascular Medicine University Hospitals Leuven University of Leuven Belgium

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