Adjunctive Antithrombotic for PCI. SCAI Fellows Course December 9, 2013

Transcription

1 Adjunctive Antithrombotic for PCI SCAI Fellows Course December 9, 2013 Theodore A Bass, MD FSCAI President SCAI Professor of Medicine, University of Florida Medical Director UF Shands CV Center,Jacksonville

2 Disclosures Adjunctive Antithrombotic Therapy for PCI: Theodore A. Bass MD, FSCAI The following relationships exist related to this presentation Consulting: none

3 ANTITHROMBOTIC DRUGS USED IN ACS/PCI I. ANTIPLATELET DRUGS COX-1 inhibitor (aspirin) P2Y 12 inhibitors (ticlopidine; clopidogrel; prasugrel; ticagrelor) Glycoprotein IIb/IIIa inhibitors (abciximab; eptifibatide; tirofiban) II. ANTICOAGULANT DRUGS Anti-Factor II (anti-thrombins) - Indirect Thrombin Inhibitors (UFH & LMWH) - Direct Thrombin Inhibitors (Bivalirudin) Anti-Factor X - Fondaparinux

4 ANTITHROMBOTIC DRUGS USED IN PCI Many options! Who wins?

5 Optimal Antithrombotic PCI Cocktail Stable CAD UA/NSTEMI STEMI

6 What s MY Antithrombotic Cocktail Stable CAD elective PCI Aspirin 325mg LD / 81mg maintenance + Clopidogrel 600mg LD / 75mg maintenance + UFH ( IU/kg)

7 Primary Endpoint: CV Death, MI, Stent Thrombosis High Platelet Reactivity Observed event rates are listed; P value by log rank test.

8 Early termination of TRIGGER-PCI at March 18, patients completed 6 months follow-up Only 1 clinical endpoint (peri-procedural MI) observed rate 0.4% Event rate, % Non-CABG TIMI major, minor or minimal bleeding Prasugrel Clopidogrel Hazard Ratio (95% CI, ) p= Days from randomization Trenk D. JACC 2012

9 Optimal Antithrombotic Cocktail Stable CAD UA/NSTEMI STEMI

10 Optimal Antithrombotic Cocktail When to consider: 1. GP IIb/IIIa inhibitors 2. Bivalirudin 3. New P2Y12 receptor antagonists

11 NSTEMI: The Role of GP IIb/IIIa inhibitors in the era of clopidogrel and direct thrombin inhibitors Shifting the paradigm!! IIb or not IIb? Major Considerations: 1) Trials performed in the good old days - Less experience; not all with stents; devices 2) Antiplatelet therapy - 1 st generation thienopyridine (ticlopidine) - 300mg LD clopidogrel William Shakespeare ( ) 3) Anticoagulant therapy - indirect thrombin inhibitors

12 ISAR-REACT 2: Abciximab vs. Placebo in ACS All patients pretreated with 600mg clopidogrel at least 2 hrs prior to PCI. 20 Death/MI/UTVR, % 15 Troponin-Positive: RR=0.71 [ ] 10 Abciximab vs. Placebo 5 0 Troponin-Negative: RR=0.99 [ ] Days after randomization Kastrati et al. JAMA. 2006;295:

13 Impact of MI and Major Bleeding (Non-CABG) in the First 30 Days on Risk of Death Over 1 Year ACUITY 30 Both MI and Major Bleed (N=94) Major Bleed Only (Without MI) (N=551) MI Only (Without Major Bleed) (N=611) No MI or Major Bleed (N=12,557) 1 Year Estimate 28.9% 12.5% 8.6% 3.4% Mortality (%) Mehran R, et al. Eur Heart J. 2009;30(12): Days From Randomization

14 ACUITY: Primary Results UFH/Enox + GP IIb/IIIa Bivalirudin + GP IIb/IIIa Bivalirudin alone Observed Rate Rate P Endpoint Value Rate P Value Net clinical outcome Ischemic events Major bleeding 11.7% 11.8% <0.001 NI 10.1% Sup 7.3% 7.7% NI 7.8% NI 5.7% 5.3% NI 3.0% <0.001 Sup NI = non-inferiority; Sup = superiority

15 Primary endpoint Death, large MI, utvr, major bleeding ISAR-REACT 4 Cumulative Incidence (%) Relative risk, 0.99 (95% CI, ) P=0.94 Abciximab 10.9% Bivalirudin 11.0% Days since Randomization Kastrati et al. NEJM 2011

16 Secondary safety endpoint Major bleeding ISAR-REACT 4 Cumulative Incidence (%) Relative risk, 1.82 (95% CI, ) P=0.02 Abciximab 4.6% Bivalirudin 2.6% Days since Randomization Kastrati et al. NEJM 2011

17 What s MY Antithrombotic Cocktail UA/NSTEMI PCI Bivalirudin: - High bleeding risk (elderly, CKD, diabetes) - Pre-treated w/clopidogrel - Unclear prior anticoagulation (safe to switch) GPI: - Already on upstream GPI - Not pre-treated w/clopidogrel (especially if high thrombotic burden) - ACS while on DAPT

18 What s MY Antithrombotic Cocktail UA/NSTEMI PCI New P2Y12 Receptor Antagonists?

19 TRITON TIMI 38 (prasugrel vs clopidogrel) PLATO (ticagrelor vs clopidogrel)

20 TRITON vs PLATO: Is there a winner? Prasugrel and ticagrelor both showed favorable efficacy and safety profiles in their respective trials and only a head-to-head comparison will be able to define the winner. Subgroup analysis will allow to define their best niche. Prasugrel. Particularly efficacious in reducing stent thrombosis, MI, utvr and great benefit in diabetics and STEMI. Contraindicated: high-risk bleeding; prior TIA/stroke Considerations: elderly, low-weight; CABG/surgery (7days). Ticagrelor. Particularly efficacious in reducing mortality (offtarget effects), OK for patients with prior TIA/ ischemic stroke. Contraindicated: high-risk bleeding; prior hemorrhagic stroke Considerations: COPD/asthma, bradyarrythmia, gout syndromes, advanced CKD, compliance (b.i.d. administration), regional differences (North America?/ASA dose), CABG/surgery (5-7days).

21 Optimal Antithrombotic PCI Cocktail Stable CAD UA/NSTEMI STEMI

22 3-Year All-Cause Mortality or Reinfarction Landmark analysis All-cause mortality or reinfarction (%) day HR (95% CI) 0.84 ( ) 4.5% 3.8% Heparin + GPIIb/IIIa (n=1802) Bivalirudin (n=1800) 3-year HR (95% CI) 0.72 ( ) p=0.005 p= % % Months Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

23 Stent Thrombosis 1-Day Landmark Analysis: Impact of Antithrombin Def/Prob Stent Thrombosis (%) Number at risk Bivalirudin UFH+GPIIb/IIIa HR [95%CI] = 5.93 [ ] P = % 0.3% Bivalirudin monotherapy Heparin + GPIIb/IIIa inhibitor Time in Days 3.0% 2.2% HR [95%CI] = 1.73 [ ] P =

24 Death, MI or Stroke in STEMI-PCI P=0.07 P=0.02 % P=0.11 N=6364 N=7544 N=3534 Drug Double dose clopidogrel Ticagrelor Prasugrel Follow-up 1 month 6-12 months 15 months

25 50 INFUSE-AMI: Infarct size at 30 days* - Primary endpoint - 40 Median [IQR] 15.1% [6.8, 22.7] Median [IQR] 17.9% [10.3, 25.4] Infarct size, %LV P= IC abciximab N=229 No abciximab N=223 JAMA 2012 *Core laboratory assessed

26 What s MY Antithrombotic Primary PCI Cocktail STEMI (# 1) Aspirin 325mg LD + Prasugrel 60mg LD + UFH (4000 IU)

27 What s MY Antithrombotic Primary PCI Cocktail STEMI (# 2) Bivalirudin in all my Primary PCI patients. Consider GPI: - STEMI while on DAPT - Already on upstream GPI - IC bolus only? (INFUSE-AMI) - Bail-out

28 NOT in my Antithrombotic Cocktail what s not good for me, may be good for others.it s a matter of taste! LMWH (enoxaparin) STEEPLE, ATOLL High maintenance dose clopidogrel - OASIS-7 Fondaparinux - OASIS-5, OASIS-6, OASIS-8

29 EMERGING ANTITHROMBOTIC DRUGS I. ANTIPLATELET DRUGS Elinogrel INNOVATE-PCI Vorapaxar TRACER/TRA 2P Cangrelor CHAMPION PHOENIX, BRIDGE II. ANTICOAGULANT DRUGS Otamixaban TAO Rivaroxaban - ATLAS 2

30 Current Controversies on DAPT in PCI Which drug? When to start? Which dose? How long? Testing?

31 Current Controversies on DAPT in PCI Which drug? When to start? Which dose? How long? Testing?

32 Clopidogrel Genetic Testing I IIa IIb III Genetic testing might be considered to identify whether a patient at high risk for poor clinical outcomes is predisposed to inadequate platelet inhibition with clopidogrel. I IIa IIb III I IIa IIb III No Benefit When a patient predisposed to inadequate platelet inhibition with clopidogrel is identified by genetic testing, treatment with an alternate P2Y 12 inhibitor (e.g., prasugrel or ticagrelor) might be considered. The routine clinical use of genetic testing to screen clopidogrel-treated patients undergoing PCI is not recommended.

33 Platelet FunctionTesting I IIa IIb III I IIa IIb III I IIa IIb III No Benefit Platelet function testing may be considered in patients at high risk for poor clinical outcomes. In clopidogrel-treated patients with high platelet reactivity, alternative agents, such as prasugrel or ticagrelor, might be considered. The routine clinical use of platelet function testing to screen clopidogrel-treated patients undergoing PCI is not recommended.

34 Thank You