Αντιαιμοπεταλιακη αγωγη (ποια, πο τε και για πο σο) Dimitrios Alexopoulos, MD, FESC, FACC Cardiology Department, Patras University Hospital, Patras, Rio, Greece. Patras University Hospital
I, Dimitrios Alexopoulos, have received honoraria for lecturing and research grants from: Astra Zeneca Patras University Hospital
P2Y12 inhibitors mechanism of action Prasugrel
Ticagrelor P2Y 12 Interaction ticagrelor binds to area distinct from ADP receptor site ADP binds to but does not activate receptor Receptor left intact upon dissociation
Mega, JAMA Nov 2010 Patras University Hospital
Study Design Day 0 Visit 1 Day 15 Visit 2 Day 30 NonSTEACS, PCI treated patient Eligible for the study Baseline LAD CBFV adequately recorded Informed consent R Ticagrelor 90mg bid Prasugrel 10mg od Ticagrelor 90mg bid Prasugrel 10 mg od Study procedure at Visit 1 and 2 10 min Resting Period Compliance with treatment assessment MACES, adverse events and bleeding events documentation BP, HR LAD bcbfv Patras University Hospital 5min Recovery periods between the infusions Adverse events monitoring throughout the procedure
An example of transthoracic Doppler echocardiography images in a single patient LAD baseline (A) and maximal at 110μg/kg/min adenosine infusion rate (B) CBFV recorded at Day 15 while under prasugrel. Same patient s images of baseline (C) and maximal at 110μg/kg/min adenosine infusion rate CBFV (D) on Day 30, while under ticagrelor. The respective ratios of maximalcbfv/baseline CBFV are shown (B, D). Alexopoulos et al, Circ Cardiovasc Interv 2013, Jun 4. [Epub ahead of print]
AUC of LAD maxcbfv at gradually increasing doses of adenosine. Alexopoulos et al, Circ Cardiovasc Interv 2013 Jun 4. [Epub ahead of print]
PLATO intent for non-invasive management: Primary composite endpoint CV death, MI or stroke (%) 20 15 10 5 0 Initially intended for non-invasive management Ticagrelor (n=2601) Clopidogrel (n=2615) p for interaction = 0.89 HR (95% CI) = 0.85(0.73 1.00); p=0.045 Days after randomisation James S, et al. BMJ 2011;342:d3527. Initially intended for invasive management Ticagrelor (n=6732) Clopidogrel (n=6676) HR (95% CI) = 0.84(0.75 0.94) 0 60 120 180 240 300 360 Primary endpoint benefit with ticagrelor was consistent with the overall PLATO trial results 14.3% 12.0% 10.7% 9.0%
Alexopoulos D et al, JACCIntv 2011,4:403
Ticagrelor vs prasugrel in acute coronary syndrome patients with high on-clopidogrel platelet reactivity following PCI Alexopoulos D, et al. JACC 2012;60:193
Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with diabetes mellitus Alexopoulos D et al. Diabetes Care 2013, in press
JACC Intv 2012;5:268
Circ Cardiovasc Interv 2012; 5:797-804
Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST elevation myocardial infarction. Alexopoulos D et al. Circ Cardiovasc Interv. 2012;5:797
. Patras University Hospital
Death/ MI/ IDR/ Stent Thrombosis within 48 Hours Event Rate (%) clopidogrel 5.9% cangrelor 4.7% Log Rank P Value = 0.006 Hours from Randomization Patient at Risk Cangrelor: 5472 5233 5229 5225 5223 5221 5220 5217 5213 Clopidogrel: 5470 5162 5159 5155 5152 5151 5151 5147 5147 Bhatt DL, Stone GW, Mahaffey KW, et al. Harrington RA. NEJM 2013 at www.nejm.org
Antiplatelet Therapy I IIa IIb III See recommendation for LOE Modified 2012 Patients with definite UA/NSTEMI at medium or high risk and in whom an initial invasive strategy is selected should receive dual antiplatelet therapy on presentation. (Level of Evidence: A) Aspirin should be initiated on presentation. (Level of Evidence: A) The choice of a second antiplatelet therapy to be added to aspirin on presentation includes 1 of the following (note that there are no data for therapy with 2 concurrent P2Y 12 receptor inhibitors, and this is not recommended in the case of aspirin allergy): Before PCI: Clopidogrel (Level of Evidence: B); or Ticagrelor (Level of Evidence: B); or An IV GP IIb/IIIa inhibitor. (Level of Evidence: A) IV eptifibatide and tirofiban are the preferred GP IIb/IIIa inhibitors. (Level of Evidence: B) At the time of PCI: Clopidogrel if not started before PCI (Level of Evidence: A); or Prasugrel (Level of Evidence: B); or Ticagrelor (Level of Evidence: B); or An IV GP IIb/IIIa inhibitor. (Level of Evidence: A) Patras University Hospital
Additional Management Considerations for Antiplatelet and Anticoagulant Therapy I IIa New 2012 IIb III Platelet function testing to determine platelet inhibitory response in patients with UA/NSTEMI (or, after ACS and PCI) on P2Y 12 receptor inhibitor therapy may be considered if results of testing may alter management. I IIa New 2012 IIb III Genotyping for a CYP2C19 loss of function variant in patients with UA/NSTEMI (or, after ACS and with PCI) on P2Y 12 receptor inhibitor therapy might be considered if results of testing may alter management. 2012 ACCF/AHA Focused Update Incorporated Into the ACCF/AHA 2007 Guidelines for the Management Patras University Hospital of Patients With Unstable Angina/ Non ST-Elevation Myocardial Infarction 56
Declining stent thrombosis rate Better implantation techniques Stronger platelet inhibition Stable patients Newer stents Patras University Hospital
Long term antiplatelet therapy Evidence for long term DAPT Prevention of stent thrombosis DAPT and bleeding complications Risks of DAPT discontinuation Triple therapy Special situations Patras University Hospital
Individualize duration of DAPT in patients at increased bleeding risk Previous stroke/tia Elderly (>75 years) Low body weight (< 60 kg) History of previous bleeding Female gender Renal failure Patras University Hospital
Long term antiplatelet therapy of the NSTEMI patient Evidence for long term DAPT Prevention of stent thrombosis DAPT and bleeding complications Risks of DAPT discontinuation Triple therapy Special situations Patras University Hospital
Triple antithrombotic therapy ESC/EACTS GUIDELINES 2011 Should only be given if a compelling indication exists (AF with CHADS score 2, mechanical valves, recent/recurrent Hx of deep venous thrombosis, PE) Only for the shortest period with frequent INR measurement (Target 2-2.5) Avoid DES (to restrict the duration to 1 month) Patras University Hospital
When to stop? DAPT should be given for 1 year following ACS Longer duration for high ishaemic risk Shorter duration for high risk of bleeding ST rate is declining due to better stents, more efficient platelet inhibition Cessation of DAPT is a major risk factor for ST in the first 6 months Patras University Hospital
When to stop? Triple therapy may be needed / particular caution To maximize the effectiveness of therapy and reduce the hazard of bleeding, ischaemic and bleeding risks should be evaluated on an individual basis. Patras University Hospital
2701 patients free of MACCE with DAPT at 12 months post DES randomized to clop + ASA vs ASA Patras University Hospital Park, NEJM 2010
TIMI major non-cabg related bleeding p=0.03 +25%* p=0.03 +25%* K-M estimated rate p=0.026 +26%* Patras University Hospital Silvain J. and Montalescot G. Circ Card Interv 2011
No link between clopidogrel withdrawal and ST > 6 months
Predictors of early discontinuation Renal impairment, prior major haemorrage, PAD Anticoagulant therapy, private hospital, no instructions Immigrants, psychotropic drugs In-hospital major bleeding Oral anticoagulation at discharge No statin prescription Patras University Hospital Ferreira-Gonzalez, Circ 2010, Rossini, AJC 2011
Recurrent stent thrombosis Prasugrel lifelong If contra? Ticagrelor? double clopidogrel? Patras University Hospital Kimura, RESTART Circ 2010
Antiplatelet Therapy I IIa IIb III See recommendation for LOE Modified 2012 For UA/NSTEMI patients in whom an initial conservative strategy is selected, if recurrent symptoms/ischemia, heart failure, or serious arrhythmias subsequently appear, then diagnostic angiography should be performed. (Level of Evidence: A) Either an IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban [Level of Evidence: A]), clopidogrel(loading dose followed by daily maintenance dose [Level of Evidence: B]), or ticagrelor (loading dose followed by daily maintenance dose [Level of Evidence: B]) should be added to aspirin and anticoagulant therapy before diagnostic angiography (upstream). (Level of Evidence: C) Patras University Hospital
Antiplatelet Therapy I IIa IIb III See recommendation for LOE Modified 2012 A loading dose of P2Y 12 receptor inhibitor therapy is recommended for UA/NSTEMI patients for whom PCI is planned. One of the following regimens should be used: a. Clopidogrel 600 mg should be given as early as possible before or at the time of PCI (Level of Evidence: B) or b. Prasugrel 60 mg should be given promptly and no later than 1 hour after PCI once coronary anatomy is defined and a decision is made to proceed with PCI (Level of Evidence: B) or c. Ticagrelor 180 mg should be given as early as possible before or at the time of PCI. (Level of Evidence: B) Patras University Hospital
Alexopoulos et al, Circ Cardiovasc Interv 2013, Jun 4. [Epub ahead of print] Patras University Hospital
JACC 2013;61:1601
Alexopoulos et al, JACC 2013, in press
INFUSE-AMI Trial 452 pts with anterior STEMI Anticipated Sx x to PCI <5 hrs, TIMI 0-20 2 flow in prox or mid LAD Primary PCI with bivalirudin anticoagulation Pre-loaded with aspirin and clopidogrel 600 mg or prasugrel 60 mg Manual aspiration R 1:1 Stratified by symptoms to angio <3 vs 3 3 hrs, and prox vs mid LAD occlusion No aspiration R 1:1 R 1:1 IC Abcx No Abcx IC Abcx No Abcx Primary endpoint: Infarct size at 30 days (cmri) 2º endpoints: TIMI flow, blush, ST-resolution, MACE (30d, 1 yr) Patras University Hospital
INFUSE-AMI: Infarct size at 30 days* Median [IQR] 15.1% [6.8, 22.7] Median [IQR] 17.9% [10.3, 25.4] Infarct size, %LV P=0.03 IC abciximab N=229 No abciximab N=223 Patras University Hospital *Core laboratory assessed
Individualize duration of DAPT in patients at increased risk for ST End-stage renal disease/hd CTO Age <65 Prior PCI IDDM Heart failure Low body weight Patras University Hospital Kimura, RESTART Circ 2010
Bellemain-Appaix JACC 2010