From STEMIs to Stents: Updates in PCI practice

From STEMIs to Stents: Updates in PCI practice Arnold Seto, MD, MPA Assistant Clinical Professor, UC-Irvine and Long Beach VA Director of Interventional Cardiology Research

Hospitalizations in the U.S. Due to Acute Coronary Syndromes (ACS) Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI 1.24 million Admissions per year STEMI.33 million Admissions per year Heart Disease and Stroke Statistics 2007 Update. Circulation 2007; 115:69-171. *Primary and secondary diagnoses. About 0.57 million NSTEMI and 0.67 million UA. 3

Main goal in STEMI: Prompt Reperfusion

Percutaneous Coronary Intervention

Case Presentation A 54 y.o. male with HTN, tobacco, presents with chest pain that started an hour ago. The nearest PCI center is 30 miles away, and it will take slightly more than an hour to transfer the patient. His BP is 150/90, O2 saturation 95% on RA, and P 90. He has no other medical problems.

EKG

Case Presentation After giving him aspirin, nitroglycerin, morphine, oxygen (MONA), and heparin, you should: A) Transfer to the nearest PCI center for emergent PCI B) Administer thrombolytics (TNKase) C) Admit to medicine, let the 2 nd year medicine resident / hospitalist decide what to do after his/her assessment

Reperfusion The medical system goal is to facilitate rapid recognition and treatment of patients with STEMI such that door-toneedle (or medical contact to-needle) time for initiation of fibrinolytic therapy can be achieved within 30 minutes or that door-to-balloon (or medical contact toballoon) time for PCI can be kept within 90 minutes.

Door to Balloon Time and Mortality A DTB time of 90 minutes or less is recommended (Class I) DTB time is tracked by registries esp ACC- NCDR and the focus of QI initiatives DTB time <90 min are now publicly reported as a quality metric, and tied to reimbursement from CMS.

Door to Balloon Time and Mortality Menees DS et al. N Engl J Med 2013;369:901-909.

Radial or femoral access in STEMI? Radial access is associated with a lower risk of vascular complications and access site bleeding. Bleeding is associated with increased mortality Transfusion risks Withholding of antiplatelet agents RIVAL study of radial vs. femoral showed a difference in mortality in STEMI subgroup.

Radial or femoral access in STEMI?

Thrombus Aspiration Routine thrombus aspiration was shown to have benefit (ST segment resolution, 1 yr mortality) in the TAPAS trial. The TASTE trial was recently published registryrandomized trial of 7000 pts.

TASTE Trial: Kaplan Meier Curves for Death from Any Cause and Hospitalization Due to Reinfarction. P = 0.63 No difference in mortality? Trend toward reduced rehospitalization P = 0.09 Fröbert O et al. N Engl J Med 2013;369:1587-1597.

STEMI: Heparin/GP2b3a or Angiomax?

Direct Thrombin Inhibitor: Bivalirudin Advantages Predictable anticoagulant response Inhibits soluble and fibrinbound thrombin Disadvantages Needs continuous infusion No antidote Cost Inhibits thrombin-induced platelet aggregation No HIT Xiao Z, Theroux P: Circulation 1998;97:251-256

HORIZONS-AMI: Time-to-Event Curves through 30 days: Net Adverse Clinical Events Treatment with bivalirudin alone compared with UFH + GP IIb/IIIa Inhibitors resulted in reduced 30-day rates of net adverse clinical events [HR=0.75, (0.62-0.92); p=0.006] Stone et al. N Eng J Med. 2008;358:2218-30.

HORIZONS-AMI: Time-to-Event Curves through 30 days: Major Bleeding HR=0.59 (0.45-0.76); p<0.0001 * 40% less bleeding in Bivalirudin group at 30 days Stone et al. N Eng J Med. 2008;358:2218-30. 21

HORIZONS-AMI Trial Demonstrated reduction in bleeding without major ischemic risks (except. Acute stent thrombosis). Also with? Mortality benefit Criticized for: Mandated use of GPIIb/IIIa Some bivalirudn pts had heparin IV bolus Change in practice to radial Change in practice to new Plavix-like drugs Bivalirudin might be best continued 2-4 hrs after PCI

EUROMAX Trial Design 2218 patients with STEMI with symptom onset >20 min and 12h Randomized in ambulance or non-pci hospital Intent for primary PCI R 1:1 Aspirin + P2Y 12 inhibitor (any) as soon as possible UFH/LMWH ± GPI Per standard practice Bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg/h infusion) + prolonged optional infusion (PCI dose or 0.25 mg/kg/h) (provisional GPI only) Primary endpoint: 30-day death or non-cabg related major bleeding Key Secondary endpoint: Death, Re-infarction or non-cabg major bleeding at 30 days Clinical FU at 30 days and 1 year clinicaltrials.gov NCT01087723

Event Rate Primary Endpoint: Death or Major Bleed, 30 day Bivalirudin Heparins with optional GPI 8.4% 5.1% Log-rank p = 0.002 Patients at risk: Days from Randomization Date Bivalirudin 1089 1038 1024 1020 1007 988 791 Heparins with optional GPI 1109 1024 1003 998 984 958 765

Subgroup Analysis: Death/Major Bleed at 30 Days (ITT) Bivalirudin (N=1089) n/n (%) Heparins with optional GPI (N=1109) n/n (%) Relative Risk (95% CI) ALL 55/1089 (5.1) 94/1109 (8.5) 0.60 [0.43, 0.82) Age Interaction P-value >65 years 39/394 (9.9) 61/434 (14.1) 0.70 [0.48, 1.03] 0.31 65 years 16/695 (2.3) 33/675 (4.9) 0.47 [0.26, 0.85] Sex Male 32/814 (3.9) 64/861 (7.4) 0.53 [0.35, 0.80] 0.47 Female 23/275 (8.4) 30/248 (12.1) 0.69 [0.41, 1.16] Diabetes Yes 12/127 (9.4) 18/169 (10.7) 0.89 [0.44, 1.77] 0.26 No 40/946 (4.2) 71/926 (7.7) 0.55 [0.38, 0.80] Arterial access site Radial 20/510 (3.9) 33/502 (6.6) 0.60 [0.35, 1.03] 0.97 Femoral 31/558 (5.6) 53/582 (9.1) 0.61 [0.40, 0.94] Vessels with stenosis >50% 1 vessel with stenosis >50% 19/591 (3.2) 33/556 (5.9) 0.54 [0.31, 0.94] 0.66 2 vessels with stenosis >50% 28/407 (6.9) 49/462 (10.6) 0.65 [0.42, 1.01] Stent type At least one drug-eluting stent 22/538 (4.1) 39/529 (7.4) 0.55 [0.33, 0.92] 0.84 All bare metal stents 16/330 (4.8) 27/336 (8.0) 0.60 [0.33, 1.10] 0.1 1.0 10.0 Bivalirudin better Heparins with optional GPI better

Outcomes, 30 days, con t Bivalirudin (N=1089) Heparins with optional GPI (N=1109) Relative risk [95% CI] P Value Reinfarction 19 (1.7) 10 (0.9) 1.93 (0.90 4.14) 0.08 Q-wave 3 (0.3) 2 (0.2) 1.53 (0.26 9.12) 0.68 Non-Q-wave 16 (1.5) 8 (0.7) 2.04 (0.88 4.74) 0.09 Stent thrombosis (ARC definition) 17 (1.6) 6 (0.5) 2.89 (1.14 7.29) 0.02 Definite 17 (1.6) 6 (0.5) 2.89 (1.14 7.29) 0.02 Probable 0 (0) 0 (0) n/a Acute ( 24 hours) 12 (1.1) 2 (0.2) 6.11 (1.37 27.24) 0.007 Subacute (>24 hours to 30 days) 5 (0.5) 4 (0.4) 1.27 (0.34 4.73) 0.75 Ischemia-driven revascularization 24 (2.2) 17 (1.5) 1.44 (0.78 2.66) 0.25 Reinfarction, ischemia-driven 29 (2.7) 21 (1.9) 1.41 (0.81 2.45) 0.23 revascularization or stent thrombosis Any stroke 6 (0.6) 11 (1.0) 0.56 (0.21 1.50) 0.24 Ischemic 6 (0.6) 9 (0.8) 0.68 (0.24 1.9) 0.46 Hemorrhagic 0 2 (0.2) Not applicable 0.50 Acquired thrombocytopenia 7 (0.7) 14 (1.4) 0.50 (0.20 1.24) 0.13 n/a: not applicable.

NCDR 2009-2011 970,865 PCIs performed for ACS. GPI used in 33.6% Safley, ACC2013 Abstract 2115M-218

RAPID Study High residual platelet reactivity (HRPR; PRU 240) was found in 44% and 60% patients (p=0.258) at 2 hours. The mean time to achieve a PRU <240 was 3±2 and 5±4 hours in the prasugrel and ticagrelor group, Parodi. JACC 2013. Morphine use had a 5.29 OR for high platelet reactivity.

Drug Eluting Stents Control Paclitaxel

Stents

Millions face risk from drug-coated stents Millions of Americans could be walking around with tiny time bombs in their hearts Potentially lethal heart devices a frightening problem for patients, doctors The FDA panel might recommend they not be used at all By Robert Bazell Chief science correspondent NBC News Nov 2006 March 2007

December 2006 FDA Findings DES are associated with a clinically important numerical excess of late stent thromboses (after 1 year post-implantation) compared to BMS; however, the magnitude of this excess is uncertain and additional data are needed. The panel reached consensus that the DES safety concerns do not outweigh their benefits compared to BMS when used within the limits of the approved labeling.

BMS and DES equivalents Vision (CoCr) Liberte/Veriflex Driver (CoCr) Integrity (CoCr) Element (CoCr) Omega (PtCr) Xience/Promus (Everolimus) Taxus Liberte (Paclitaxel) Endeavor (Zotarolimus) Resolute Integrity (ZES) Promus Element (EES) Taxus Element aka ION (PES) BxVelocity Cypher (Sirolimus, discontinued)

Stents

EES has less stent thrombosis than BMS?

Stents: Summary DES have been shown to have reduced restenosis rates compared with BMS. 2 nd generation stents (Xience, Endeavor/ Resolute) carry a lower risk of stent thrombosis than 1 st generation stents (Taxus, Cypher) 12 months of dual antiplatelet therapy may be unnecessary for DES.

Patients on DAPT (%) Optimize Trial: DAPT Usage Time After Initial Procedure

Cumulative Incidence of NACCE (%) Primary Endpoint: NACCE at 1 Year (All-Cause Death, MI, Stroke, Major Bleeding) 15 10 5 3M DAPT 12M DAPT Log-Rank P = 0.84 HR 1.03 (0.77 1.38) Non-inferiority P-value = 0.002 6.0 5.8 0 0 3 6 9 12 Time After Initial Procedure (Months) Month 0 1 3 6 12 No. at risk 1563 1520 1504 1468 1384 No. events 18 25 11 18 21 No. at risk 1556 1514 1497 1466 1381 No. events 16 25 11 16 22

Conclusions In patients from daily clinical practice with stable coronary artery disease or low risk ACS undergoing PCI with E- ZES, short-term DAPT (3 months) is noninferior to long-term DAPT (12 months) in terms of the occurrence of death, MI, stroke, or major bleeding.

Bioabsorbable vascular scaffold

Schömig A. N Engl J Med 2009;361:1108-1111.

Endpoint (%) TRITON: Results Balance of Efficacy and Safety 15 10 CV Death / MI / Stroke Clopidogrel Prasugrel 12.1 9.9 138 events HR 0.81 (0.73-0.90) P=0.0004 NNT = 46 5 0 TIMI Major NonCABG Bleeds 0 30 60 90 180 270 360 450 Adapted with permission from Wiviott SD et al NEJM 357:2007 Days Prasugrel Clopidogrel 2.4 1.8 35 events HR 1.32 (1.03-1.68) P=0.03 NNH = 167 42

Bivalirudin Fondaparinux Prasugrel Ticagrelor