Which is the best anticoagulant during primary PCI (p-pci) for STEMI?

Transcription

1 ALPIC 2016 Friday, March 25 th, 2016 Round Table: Antithrombotic therapy for ACS-PCI Which is the best anticoagulant during primary PCI (p-pci) for STEMI? George Hahalis Associate Professor of Cardiology University of Patras

2 Σύγκρουση συμφερόντων: Καμία σχετικά με αυτή την ομιλία No conflict of interest relevant for this lecture

3 Hell J Cardiol, September 2015 Expert Perspective PARENTERAL ANTICOAGULANTS IN ACUTE CORONARY SYNDROMES AND INTERVENTIONAL CARDIOLOGY A Consensus Document Task Force on the Management of Parenteral Anticoagulation in Acute Coronary Syndromes and Interventional Cardiology of the Institute for the Study and Education on Thrombosis and Antithrombotic Therapy (I.S.E.T.A.T) George Hahalis 1, Periklis Davlouros 1, Grigorios Tsigkas 1, Emmanouel Vavouranakis 2, John Goudevenos 3, Alexandros D.Tselepis 3, Dimitrios C. Alexopoulos 1,4 1 University of Patras, Greece; 2 University of Athens, Greece 3 University of Ioannina, Greece; 3 University of Athens, Greece

4 Understanding Anticoagulant Superiority Focus on drug properties, treatment strategy & procedure type Treatment strategy specific More conservative vs. earlier invasive Drug specific Efficacy: less ischemic complications Safety: less bleeding risk Cost: Euro Procedure specific Transradial vs. transfemoral PCI

5 UFH Enoxaparin Fonda Factor Xa:IIa inhibition 1:1 3-4:1 100% Xa 100% IIa Anticoagulation Yes No No No monitoring Inhibits fibrin-bound No No No Yes thrombin Activates platelets Yes Less Less Inhibits CKD No dose adjustment Dose adjustment Renal excretion Risk of HIT Yes Reduced Low No Antidote Yes Partial No No Dose adjustment CKD = Chronic kidney disease HIT = Heparin-Induced Thrombocytopenia

6 Inactivation of Coagulation Factors by Anticoagulant Drugs XIIa XIa UFH/AT UFH/AT XIII V IXa UFH/AT XIIIa X UFH/AT LMWH/AT Tissue Factor Pathway Inhibition (TFPI) TF/VIIa Xa Anti-Xa Fondaparinux/AT Anti IIa-/Anti-Xa UFH/AT, LMWH/AT Prothrombin V, Ca 2+ IIa (thrombin) Anti-IIa Fibrin generation Platelet aggregation & = activation of coagulation factors = inactivation of coagulation factors

7 Algorithm of Parenteral Anticoagulant use (1) Conservative management scheduled* NSTEACS Nontreperfused STEMI Thrombolysed STEMI Invasive management scheduled* Fondaparinux Enoxaparin UFH Less bleedings (vs. Enoxa) Less reinfarctions (vs. UFH) Any of the 3 anticoagulants * Without history of HIT for heparins Without severe chronic kidney disease for non-ufh anticoagulants Early, elective coronary angiography, i.e. within 1-3 days is possible Very strong recommendation Strong recommendation Less strong recommendation

8 Algorithm of Parenteral Anticoagulant use (2) Conservative management scheduled* NSTEACS Nontreperfused STEMI Thrombolysed STEMI Invasive management scheduled* Fondaparinux Enoxaparin UFH Less death/mis (vs. placebo) Less reinfarctions (vs. UFH) Any of the 3 anticoagulants * Without history of HIT for heparins Without severe chronic kidney disease for non-ufh anticoagulants Early, elective coronary angiography, i.e. within 1-3 days is possible Very strong recommendation Strong recommendation Less strong recommendation

9 Algorithm of Parenteral Anticoagulant Use (3) PCI Average bleeding risk* Transfemoral (provisional GPI) Any bleeding risk* Transradial High bleeding risk Transfemoral (provisional GPI) UFH (70 U/kg) UFH ( U/kg) Enoxaparin Enoxaparin * Without history of HIT for heparins Without severe chronic kidney disease for non-ufh anticoagulants UFH Enoxaparin Very strong recommendation Strong recommendation Less strong recommendation

10 Enoxa Enoxaparin vs. UFH in STEMI PCI Meta-analysis Enoxaparin UFH Mortality Major bleedings P< % P=NS P< ,1% 6,0% 17% 2,9% 3,5% 28% 2,6% 4,56% P=NS 1,8% 1,9% Primary PCI Secondary PCI Primary PCI Secondary PCI Silvain J, et al. BMJ 2012;344:e553 doi: /bmj.e553

11 Fonda OASIS 6: Fondaparinux or control* for <8 days in patients with STEMI 45% underwent thrombolysis (73% with SK) & 53% primary PCI From day 3 9, all patients received either fondaparinux or placebo Death/MI at 30 days (main outcome measure) HR (95% CIs) UFH not indicated-78% thrombolyzed- (Fonda vs. Placebo: Similar bleeding rates 14% vs. 11.2%) UFH indicated-16% thrombolyzed- (Fonda vs. UFH: Similar bleeding rates: 8.7% vs. 8.3%;) Fondaparinux better Placebo or UFH better *Placebo if UFH not indicated [stratum 1] or UFH for <48 hours followed by placebo for up to 8 days [stratum 2] JAMA 2006

12 Fonda OASIS 6: Fondaparinux or control* in STEMI patients 45% underwent thrombolysis (73% with SK) & 53% primary PCI From day 3 9, all patients received either fondaparinux or placebo Death/MI at 30 days P=0.003 HR (95% CIs) No reperfusion (15.1% vs. 12.2%) P=0.03 Thrombolysis (13.6% vs %) P=0.13 Primary PCI (4.9 % vs. 6.0 %) Fondaparinux better Placebo or UFH better *Placebo if UFH not indicated [stratum 1] or UFH for <48 hours followed by placebo for up to 8 days [stratum 2] JAMA 2006

13 Fonda Fondaparinux vs. Heparins in ACS in OASIS 5 & 6 (n=26512) Enoxaparin / UFH Fondaparinux Ischemic complications* 8,0% P=0.03-9% 7,2% Major bleedings 3,4% P< % 2,1% Net clinical benefit** 10,8% P= % Fondaparinux is contraindicated in PCI 9,4% Invasive strategy (n=19085) Catheter thrombus 0,2% HR: 3.98 ( ) 0,9% MI-Risk: Χ 6,5 CVA-Risk: Χ 9,5 (n=6290) * Death, MI, CVA ** Death, MI, CVA, Major bleeding Mehta SR, et al. Circulation 2008;118:2038

14 Biva GPI use in vs. Heparin (p-pci or pred. p-pci)trials GPI + UFH GPI + Primary PCI: 100% Primary PCI: 100% Primary PCI: 56% Clopi:100% Clopi:50% Clopi:47% 98% 69% GPI+UFH use declining Mortality Bleeding 7.5% HORIZON AMI (2008) vs. UFH 100 U/kg (n=3602) Bleeding New 2PY12 antag. use increasing 11.5% EUROMAX (2013) vs. UFH 100 U/kg (n=2218) 26% Mortality Bleeding 4.6% MATRIX (2015) vs. UFH 100 U/kg (n=7213)

15 Biva vs. UFH in p-pci With balanced GPI use between groups UFH HEAT-PPCI P-PCI:100% Ischemic complications BRIGHT P-PCI: 89% P=0.01 5,7 % 8.7 % Major bleedings P=NS 3,1 % 3,5 % Ischemic complications P=NS 5,8 % 5.0 % Major bleedings 1,5 % P=NS 0,5 % HEAT PPCI (2013) vs. UFH 70 U/kg (n=1829) BRIGHT (2014) vs. UFH 100 U/kg (n=2194)

16 Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox 2015 MATRIX : Heparin vs. Biva Patients with STEMI (56%) & NSTEMI (40%) Pre-lab ADP antagonist: clopidogrel 47%, ticagrelor or prasugrel 36% CONCLUSIONS UFH (n = 3,603) (n = 3 610) First co-primary outcome: Death, MI, or stroke 10,9 % P=NS 10.3 % Second co-primary outcome: Death, MI, stroke, BARC 3/5 bleed In patients with an ACS, the rates of MACE and net adverse clinical events were not significantly lower Stent thrombosis (definite): 0.6% vs. 1.0% 12,4 % P=NS (p = 0.048) for heparin vs. bivalirudin with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-pci bivalirudin infusion than with no post-pci 11.2 % Major bleeding (BARC 3 or 5): 2.5% vs. 1.4% (p = 0.001) for heparin vs. bivalirudin infusion. Valdimigli M. et at NEJM. September 1, 2015 DOI: /NEJMoa

17 Biva Heparins vs. in PCI before MATRIX- (Meta-analysis in patients) Ischemic complications Major bleedings MACE MI HR (95% CIs) 1 09 ( ) ) Mortality 0.99 ( ) 1 12 ( ) Acute stent thrombosis 3 86 ( ) No relation between the reduction of bleeding and the reduction of mortality with bivalirudin across trials Provisional GPI (n=8994) GPI (n=6710) 0 78 ( ) P=NS 1 07 ( ) P=NS better Heparins better Lancet 2014; 384: 599

18 GPIs in primary PCI in the Era of New, Potent Antiplatelet Agents 54% 41% USA UK 28% USA 11,0% Rio, Univers. Hospital 15% MATRIX 14% UK HEAT PPCI National CV National CV Data CathPCIData CathPCI Registry Registry Newer Series Older

19 Biva PCI trials with equivalent GPI use between anticoagulant groups REPLACE 1 (2004) (n=532 B H} Clopidogrel:100% UFH:60-70 U/kg after PCI:(-) TRadial:0% ACUITY (2006) (n=4604 B H) Clopidogrel:100% UFH:60 U/kg (Enoxa:0.75 mg/kg IV) after PCI:(-) TRadial:0% HEAT-PPCI (2014) (n=905 B H) Clopidogrel:11% UFH:70 U/kg after PCI:(+) TRadial:81% BRIGHT (2015) (n=735 B H) Clopidogrel:100% UFH:100 U/kg after PCI:(+) TRadial:79% MATRIX (2015) 7213 N GPI % TOTAL (6776 B H)

20 PCI trials with equivalent GPI use between anticoagulant groups Biva REPLACE ACUITY 2006 Death, n Death Heparins, n Major bleedings (BARC>3), n Major bleedings (BARC>3) Heparins, n HEAT-PPCI BRIGHT 2015 TOTAL (n=13569) Heparins = -12 deaths TOTAL (%) 1.9% 1.68% = -11.6% Heparins = + 23 major bleedings 4.28% 4.50% = +5.0%

21 Anticoagulants in primary, secondary, urgent or elective PCI PCI, p-pci Average bleeding risk* Transfemoral (provisional GPI) Any bleeding risk* Transradial High bleeding risk Transfemoral (provisional GPI) UFH (70 U/kg) UFH ( U/kg) Very strong recommendation Enoxaparin Enoxaparin Strong recommendation UFH Less strong recommendation Enoxaparin * Without history of HIT for heparins Without severe chronic kidney disease for non-ufh anticoagulants

22 Biva Almost Both a Perpetrator and a Victim Subjected to: perceived risks of bleeding (bivalirudin scientific world determined to sacrifice Iphigeneia Although doctors wanted heparin to die (i.e., UFH => i.e., the bleeding beast ) Heparin refused to die but bivalirudin also subjected to: unforeseeable 2PY12 antagonist developments declining GPI use Nonetheless, bival. is neither that bad, nor that good radical radial artery use increase for coronary procedures deserves an indication for (primary) PCI faulty or outdated trial designs => faulty meta-analysis conclusions

23 Anticoagulants in primary, secondary, urgent or elective PCI Average bleeding risk* Transfemoral (provisional GPI) PCI, p-pci Any bleeding risk* Transradial High bleeding risk Transfemoral (provisional GPI) UFH (70 U/kg) UFH ( U/kg) Very strong recommendation Enoxaparin Enoxaparin Strong recommendation Less strong recommendation UFH Enoxaparin * Without history of HIT for heparins Without severe chronic kidney disease for non-ufh anticoagulants

24 The final clinical scenario, appropriate for the ALPIC 2016 meeting Which anticoagulant in p-pci while on oral anticoagulation will be left for possible discussion

25 ALPIC 2016 Thank you for your attention