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

3

Hospitalizations in the U.S. Due to Acute

Coronary Syndromes (ACS)

Acute Coronary

Syndromes*

1.57 Million Hospital Admissions - ACS

UA/NSTEMI† STEMI

1.24 million Admissions per year

.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.

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 2nd 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-to-

needle (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–to-

balloon) time for PCI can be kept within 90 minutes.

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 2nd year medicine resident /

hospitalist decide what to do after his/her assessment

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 registry-

randomized trial of 7000 pts.

TASTE Trial:

Kaplan–Meier Curves for Death from Any

Cause and Hospitalization Due to

Reinfarction.

Fröbert O et al. N Engl J Med

2013;369:1587-1597.

P = 0.09

P = 0.63

No difference in mortality

? Trend toward reduced

rehospitalization

STEMI: Heparin/GP2b3a or Angiomax?

Direct Thrombin Inhibitor: Bivalirudin

Predictable anticoagulant

response

Inhibits soluble and fibrin-

bound thrombin

Inhibits thrombin-induced

platelet aggregation

No HIT

Needs continuous infusion

No antidote

Cost

Disadvantages Advantages

Xiao Z, Theroux P: Circulation 1998;97:251-256

20

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.

21

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.

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

2218 patients with STEMI with symptom onset >20 min and ≤12h

Randomized in ambulance or non-PCI hospital

Intent for primary PCI

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)

Aspirin + P2Y12 inhibitor

(any) as soon as possible R

1:1

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

EUROMAX Trial Design

clinicaltrials.gov NCT01087723

Days from Randomization Date

Eve

nt

Rate

Bivalirudin 1089 1038 1024 1020 1007 988 791

Heparins with optional GPI

1109 1024 1003 998 984 958 765

Bivalirudin

Heparins with optional GPI 8.4%

Log-rank p = 0.002

Patients at risk:

Primary Endpoint: Death or Major Bleed, 30 day

5.1%

Bivalirudin (N=1089) n/N (%)

Heparins with optional GPI

(N=1109) n/N (%)

Relative Risk (95% CI)

Interaction P-value

ALL 55/1089 (5.1) 94/1109 (8.5) 0.60 [0.43, 0.82)

Age

>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]

Subgroup Analysis: Death/Major Bleed at 30 Days (ITT)

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 revascularization or stent thrombosis

29 (2.7) 21 (1.9) 1.41 (0.81–2.45) 0.23

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

Parodi. JACC 2013.

Morphine use had a 5.29 OR for high platelet

reactivity.

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,

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)

BxVelocity

Xience/Promus (Everolimus)

Taxus Liberte (Paclitaxel)

Endeavor (Zotarolimus)

Resolute Integrity (ZES)

Promus Element (EES)

Taxus Element aka ION (PES)

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.

2nd generation stents (Xience, Endeavor/

Resolute) carry a lower risk of stent thrombosis

than 1st generation stents (Taxus, Cypher)

12 months of dual antiplatelet therapy may be

unnecessary for DES.

Optimize Trial: DAPT Usage P

ati

en

ts o

n D

AP

T (

%)

Time After Initial Procedure

Primary Endpoint: NACCE at 1 Year (All-Cause Death, MI, Stroke, Major Bleeding)

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

Log-Rank P = 0.84

HR 1.03 (0.77 – 1.38)

Cu

mu

lati

ve

In

cid

en

ce

of

NA

CC

E (

%)

Time After Initial Procedure (Months)

0 12

0

10

15

5

3 6 9

6.0 5.8

12M DAPT

3M DAPT

Non-inferiority

P-value = 0.002

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 non-

inferior 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.

42

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81

(0.73-0.90)

P=0.0004

Prasugrel

Clopidogrel

Days

En

dp

oin

t (%

)

12.1

9.9

HR 1.32

(1.03-1.68)

P=0.03

Prasugrel

Clopidogrel 1.8

2.4

138

events

35

events

Balance of

Efficacy and Safety

CV Death / MI / Stroke

TIMI Major

NonCABG Bleeds

NNT = 46

NNH = 167

Adapted with permission from Wiviott SD et al

NEJM 357:2007

TRITON: Results

Prasugrel

Ticagrelor

Bivalirudin

Fondaparinux