ACS guidelines -Choose the right drugs and strategies ... · Assoc.Prof.Dilok Piyayotai Division of...

Assoc.Prof.Dilok Piyayotai

Division of Cardiology

Thammasat University Hospital

ACS guidelines -Choose the right drugs and strategies before referal

เครือข่ายบริการสาธารณสุขที ่6

Guidelines Pertaining to ACS An Expanding Portfolio

ACC/AHA guidelines • 2011 ACC/AHA/SCAI Guideline on PCI • 2013 ACC/AHA Guideline on STEMI • 2014 ACC/AHA Guideline on NSTE-ACS • 2015 ACC/AHA/SCAI Focused Update on Primary PCI

for STEMI • 2016 ACC/AHA Focused Update on DAPT Duration ESC guidelines • 2012 STEMI Guideline • 2015 NSTEMI Guideline

* O’Connor RE, Brady W, Brooks SC, Diercks D, Egan J, Ghaemmaghami C, Menon V, O’Neil BJ, Travers AH, Yannopoulos D. “Part 10: acute coronary

syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care”. Circulation.

2010;122(suppl 3):S787-S817. http://circ.ahajoumals.org/content/122/18_suppl_3/S787

http://circ.ahajoumals.org/content/122/18_suppl_3/S787

http://circ.ahajoumals.org/content/122/18_suppl_3/S787

**Afolabi BA, Novaro GM, Pinski SL, Fromkin KR, Bush HS. Use of the prehoapital ECG improves door to balloon times in ST segment elevation myocardial

infarction irrespective of time of day or day of week. Emerg Med J. 2007;24:588-591

*** O’Connor, RE AL, Ali, brady , WJ, Ghaemmaghami CA, Menon V, Welsford M, shuster M. . Part 9: acute coronary syndromes: 2015 American Heart

Association Guidelines Update for Cardiopulmonary Resuscitation

and Emergency Cardiovascular Care. Circulation 2015;132(suppl2):S483-S500

• STEMI intervention

• Fibrinolytics

• Use of appropriate antiplatelet agents

• Use of appepropriate anticoagulants

The interesting topics in STEMI

The Goal of STEMI Intervention

• Restore flow in the culprit artery and optimize myocardial perfusion

• Preserve LV function.

• Reduce MI complications

• Reduce mortality.

Geoffrey Hartzler, M.D. First Primary Angioplasty in AMI, 1979

1946 - 2012

Angioplasty reduces mortality and morbidity

Primary PCI vs. Thrombolysis in ST-Elevation Myocardial Infarction: Meta-analysis (23 Randomised controlled trials, N=7,739)

Death Nonfatal MI

Short-term Outcomes (4-6 weeks)

Fre

qu

ency

(%

)

P<.0001

P<.0001

P=.0002

P<.0001 PPCI

Thrombolytic therapy

Recurrent Ischemia

Death, Nonfatal, Reinfarction, or Stroke

Based on Keeley EC, et al. Lancet. 2003;361:13-20.

11

Time from symptom onset to treatment predicts 1 Year Mortality—Primary PCI

The relative risk of 1 year mortality increases by 7.5% for each 30 minute delay.

De Luca G, et al. Circulation. 2004;109:1223-1225.

Y=2.86 (± 1.45) + 0.0045X1 + 0.000043X2 P<.001

Roughly 1% every 3 minutes

Primary PCI in STEMI

ACC/AHA STEMI guidelines 2015

Immediate transfer⟸Failed

Routine transfer 3-24 hr⟸Successful

Pharmaco-invasive Strategy for STEMI Transfer to a PCI-Capable Hospital After Fibrinolytic Therapy

Transfer of Patients With STEMI to a PCI-Capable Hospital for Coronary Angiography After Fibrinolytic Therapy

Transfer to a PCI-capable hospital for coronary angiography

is reasonable for patients with STEMI who have received

fibrinolytic therapy even when hemodynamically stable* and

with clinical evidence of successful reperfusion.

Angiography can be performed as soon as logistically

feasible at the receiving hospital, and ideally within 24

hours, but should not be performed within the first

2 to 3 hours after administration of fibrinolytic

therapy.

I IIa IIb III B

*Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or symptomatic supraventricular tachyarrhythmias, and

spontaneous recurrent ischemia.

Prefer 3-24 Hr after fibrinolysis

Indications for Transfer for Angiography After Fibrinolytic Therapy

*Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia.


Immediate transfer⟸Failed

Routine transfer 3-24 hr⟸Successful

Risk-Benefits of N-IRA PCI

? Benefits

• Decrease infarct size by increasing collateral flow

• Reduce recurrent MI – Plaque stabilisation

• ? Reduce length of stay

• Reduce recurrent ischaemia – ? Improve prognosis

? Risks

• Increase infarct size – N-IRA PCI related

• Contrast induced nephropathy

• Bleeding

• Increase cost with no clinical benefit

Culprit artery–only versus multivessel PCI

PCI-CLARITY: Event rates following PCI

Sabatine MS et al. JAMA 2005; 294:1224-1232.

End point Clopidogrel pretreatment (%)

No pretreatment (%)

Adjusted odds ratio (95% CI)

p

CV death/MI/stroke*

3.6 6.2 0.54 (0.35-0.85)

0.008

CV death/MI 3.3 5.4 0.58 (0.36-0.94)

0.03

CV death 1.4 2.6 0.49 (0.24-1.03)

MI 1.9 3.1 0.60 (0.33-1.11)

Stroke 0.4 1.2 0.35 (0.11-1.11)

*Primary end point

PLATO STEMI-Hierarchical testing of major efficacy endpoints

Endpoint* Ticagrelor (n=4,201)

Clopidogrel (n=4,229)

HR for ticagrelor (95% CI)

p-value†

Primary endpoint, %

CV death + MI + stroke

9.3

11.0

0.85 (0.74–0.97)

0.02

Secondary endpoints, %

Total death + MI + stroke

CV death + MI + stroke + ischaemia + TIA + arterial thrombotic events

MI

CV death

Stroke

9.7

13.4

4.7

4.5

1.6

11.5

15.4

6.1

5.4

1.0

0.84 (0.73–0.96)

0.86 (0.76–0.96)

0.77 (0.63–0.93)

0.84 (0.69–1.03)

1.45 (0.98–2.17)

0.01

0.01

0.01

0.09

0.07

All-cause mortality 4.9 6.0 0.82 (0.68–0.99) 0.04

The percentages are K-M estimates of the rate of the endpoint at 12 months. Patients could have had more than one type of endpoint.

†By univariate Cox model

Adjunctive Antithrombotic Therapy to

Support Reperfusion With Primary PCI

‡The recommended ACT with planned GP IIb/IIIa receptor antagonist treatment is 200 to 250 s.

§The recommended ACT with no planned GP IIb/IIIa receptor antagonist treatment is 250 to 300 s (HemoTec device) or 300

to 350 s (Hemochron device).

Harmonizing Outcomes with Revascularization and Stents in AMI

3602 pts with STEMI with symptom onset ≤12 hours

Emergent angiography, followed by triage to…

Primary PCI CABG – Medical Rx –

UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide)

Bivalirudin monotherapy

(± provisional GP IIb/IIIa)

Aspirin, thienopyridine R

1:1

3006 pts eligible for stent randomization R

3:1

Bare metal EXPRESS stent Paclitaxel-eluting TAXUS stent

Clinical FU at 30 days, 6 months, 1 year, and then yearly through 3 years; angio FU at 13 months

Stone, GW N Engl J Med 2008;358:2218-30.

0

5

10

15

20

Horizons-Primary PCI Cohort (N=3,340)

30-day Event rates

RR = 0.99 [0.75, 1.32]

Psup = 1.00

RR = 0.59 [0.46, 0.77]

PNI ≤ 0.0001 Psup ≤ 0.0001

RR = 0.75 [0.62, 0.92]

PNI ≤ 0.0001 Psup = 0.005

*Not related to CABG

**MACE = All cause death, reinfarction, ischemic TVR or stroke

Heparin + GPIIb/IIIa inhibitor (n=1662) Bivalirudin monotherapy (n=1678)

Net adverse clinical Major bleeding* MACE** events

% 12.3

9.2 8.6

5.1 5.5 5.4

3-year MACE Components*

UFH + GPI (N=1802)

Bivalirudin (N=1800)

HR [95%CI] P Value Number

needed to treat

Death 7.7% 5.9% 0.75 (0.58,0.97) 0.03 54

- Cardiac 5.1% 2.9% 0.56 (0.40,0.80) 0.001 45

- Non cardiac 2.8% 3.1% 0.62

Reinfarction 8.2% 6.2% 0.76 (0.59,0.92) 0.04 52

- Q-wave 3.8% 3.4% 0.61

- Non Q-wave 4.9% 3.2% 0.009 58

Death or reinfarction 14.5% 11.3% 0.72 (0.58,0.91) 0.005 31

Ischemic TVR 12.1% 14.2% 0.06

Stroke 2.0% 1.7% 0.50

Stone, GW Lancet 2011 Published online June 13. DOI:10.1016/S0140-6736(11)60764-2

3-year Bleeding Endpoints UFH + GPI (N=1802)

Bivalirudin (N=1800)

HR (95% CI) P Value Number needed to treat

Major bleeding, non-CABG

10.5% 6.9% 0.64 (0.51-0.80) 0.0001 28

Major bleeding, including CABG

12.8% 8.9% <0.0001 25

Blood transfusion 5.1% 3.5% 0.01 61

TIMI Major or Minor 10.9% 7.0% <0.0001 26

TIMI Major 6.1% 4.1% 0.007 51

TIMI Minor 5.0% 3.2% 0.007 56

GUSTO (any) 12.7% 8.8% 0.0001 26

GUSTO severe/life-threatening

0.9% 1.0% 0.74

GUSTO moderate 6.3% 4.7% 0.03 63

GUSTO mild 6.2% 4.0% 0.003

Stone, GW Lancet 2011 Published online June 13. DOI:10.1016/S0140-6736(11)60764-2

How Effective are Antithrombotic Therapies in PPCI

Characteristic Bivalirudin (%) Heparin (%)

P2Y12 use - Any 99.6 99.5

- Clopidogrel 11.8 10.0

- Prasugrel 27.3 27.6

- Ticagrelor 61.2 62.7

GPI use 13.5 15.5

Radial arterial access 80.3 82.0

PCI performed 83.0 81.6

Event curve shows first event experienced

Bivalirudin Heparin n % % n

Minor Bleed 83 9.2 % v 10.8 % 98

Major or Minor 113 12.5 % v 13.5 % 122

Minor Bleed P=0.25 Major or Minor P=0.54

Major Bleed BARC grade 3-5 Minor Bleed BARC grade 2

Reperfusion at a Non–PCI-Capable Hospital

Guideline for STEMI

Indications for Fibrinolytic Therapy When There Is a >120-Minute Delay From FMC to Primary PCI

Adjunctive Antithrombotic Therapy to Support Reperfusion With Fibrinolytic Therapy

Adjunctive Antithrombotic Therapy to Support Reperfusion With Fibrinolytic Therapy (cont.)

New NSTE-ACS guidelines

The most confusing issues in NSTE-ACS management

• Diagnosis : rule-in & rule-out protocol

• Risk stratification

• Invasive vs ischemia-driven management


• Use of appropriate anticoagulants

Marco Roffi* et al. Eur Heart J 2015,

0 h/3 h rule-out algorithm of of NSTEMI using hs-troponin



5 12

3

52

5

Benefit of Risk Stratification in NSTE-ACS patients

1) selection of the site of care:

- coronary care unit

- monitored step-down unit

- outpatient setting

2) selection of therapy:

- GP IIb/IIIa inhibitors

- invasive management strategy

Rationale for Risk Stratification in NSTE-ACS patients

- Focuses on history

- Physical findings

- ECG findings

- Biomarkers of cardiac injury

(Cardiac specific Troponin)

- Scoring system e.g. TIMI score, GRACE risk score

Summary of recommendations for prognosis early risk stratification

✔

✔

✔

✔

EKG • Transient ST changes (>0.5 mm.)during

symptom at rest strongly suggest ischemia and underlying severe CAD

• Marked symmetrical precordial T-wave inversion (> 2 mm) suggests acute ischemia, particular due to critical stenosis of LAD

EKG

• Completely normal ECG does not exclude NSTE-ACS, 1-6% will have MI

• Nonspecific ST-T changes (defined as ST deviation of < 0.5 mm. or T-wave inversion of < 2 mm. are less helpful diagnostically

Troponin Predicts Mortality

Antman TM, Tenasijevic MJ, Thompson B, et al. Cardiac-specific troponin I

levels to predict the risk of mortality in patients with acute coronary

syndromes. N Engl J Med 1996;335:1342-1349.

Risk Assessment Tools

• The TIMI risk score

• The GRACE risk model

• The PURSUIT risk score

• Etc.

TIMI Risk Score* for NSTE-ACS

TIMI Risk

Score

All-Cause Mortality, New or Recurrent MI, or

Severe Recurrent Ischemia Requiring Urgent

Revascularization Through 14 d After

Randomization, %

0–1 4.7

2 8.3

3 13.2

4 19.9

5 26.2

6–7 40.9

*The TIMI risk score is determined by the sum of the presence of 7

variables at admission; 1 point is given for each of the following variables:

≥65 y of age; ≥3 risk factors for CAD; prior coronary stenosis ≥50%; ST

deviation on ECG; ≥2 anginal events in prior 24 h; use of aspirin in prior 7

d; and elevated cardiac biomarkers.

Calibration of Simplified Global Registry of ACS

Mortality Model

Invasive vs Conservative Strategy Clinical Trials

TIMI IIIB (94)

Conservative Strategy Favored

N=920

Invasive Strategy Favored

N=7,018

VANQWISH (98)

MATE

FRISC II (99)

TACTICS- TIMI 18 (01)

VINO

RITA-3 (02)

TRUCS

ISAR- COOL

ICTUS (05)

No difference N=2,874

Weight of the evidence

Risk criteria mandating invasive strategy


Rx strategy Action at non-PCI hospital

Immediate Invasive ( < 2 hours)

Immediate Transfer to PCI center

Early invasive (< 24 hours)

Same day Transfer to PCI center

Invasive (< 72 hours)

Transfer to PCI center

74

NB: Continuation of ticagrelor or prasugrel beyond 12 months is outside the label of both drugs

Recommended treatment algorithm in NSTE-ACS

• Early management (angiography or initial medical management)

• Invasive management (PCI)

• Late/post- hospital care

Pathway stage

• Initiate ticagrelor or clopidogrel, preferably ticagrelor

• (NB: prasugrel is not a recommended option at this stage)

• Initiate/continue ticagrelor or clopidogrel, or initiate prasugrel (only after coronary anatomy has been defined)

P2Y12 recommendation

• Medically managed: Ticagrelor or clopidogrel for up to 12 months, preferably ticagrelor

• Stent: Ticagrelor, prasugrel or clopidogrel for at least 12 months, preferably ticagrelor or prasugrel

NSTE-ACS:

Definite or Likely

Ischemia-Guided strategy Early Invasive Strategy

Initiate DAPT and Anticoagulant Therapy

1. ASA (Class I; LOE: A)

2. P2Y12 inhibitor (in addition to ASA) (Class I; LOE B):

● Clopidogrel or

● Ticagrelor

3. Anticoagulant:

● UFH (Class I; LOE B) or

● Enoxaparin (Class I; LOE: A) or

● Fondaparinux (Class I; LOE: B)

Initiate DAPT and Anticoagulant Therapy

1. ASA (Class I; LOE: A)

2. P2Y12 inhibitor (in addition to ASA) (Class I; LOE: B):

● Clopidogrel or

● Ticagrelor

3. Anticoagulant:

● UFH (Class I; LOE B) or


● Fondaparinux (Class I; LOE B) or

● Bivalirudin (Class I; LOE B)

Can consider GPI in addition to ASA and P2Y12 inhibitor in

high-risk (eg, troponin positive) patients (Class IIb; LOE B)

● Eptifibatide

● Tirofiban

Medical therapy

chosen based on cath

findings

Therapy

Ineffective Therapy

Effective

PCI with stenting

Initiate/continue antiplatelet and anticoagulant

therapy

1. ASA (Class I; LOE: B)

2. P2Y12 inhibitor (in addition to ASA):

● Clopidogrel (Class I; LOE: B) or

● Prasugrel (Class I; LOE: B) or

● Ticagrelor (Class I: LOE: B)

3. GPI (if not treated with bivalirudin at time of

PCI)

● High risk features, not adequately pretreated

with clopidogrel (Class I; LOE: A)

● High-risk features adequately pretreated

with clopidogrel (Class IIa; LOE: B)

4. Anticoagulant:


● Bivalirudin (Class I; LOE: B) or

● Fondaparinux as the sole anticoagulant

(Class III: Harm; LOE: B) or

● UFH (Class I; LOE: B)

Late hospital/post hospital care 1. ASA indefinitely (Class I; LOE: A) 2. P2Y12 inhibitor (clopidogrel or ticagrelor), in addition to ASA, up to 12 mo if medically treated (Class I; LOE: B) 3. P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor), in addition to ASA, at least 12 mo if treated with coronary stenting (Class I; LOE: B)

CABG

Initiate/continue ASA therapy and

discontinue P2Y12 and/or GPI therapy

1. ASA (Class I; LOE: B)

2. Discontinue clopidogrel/ticagrelor 5

d before, and prasugrel at least

7 d before elective CABG

3. Discontinue clopidogrel/ticagrelor up

to 24 h before urgent CABG (Class I;

LOE: B). May perform urgent CABG

<5 d after clopidogrel/ticagrelor and

<7 d after prasugrel discontinued

4. Discontinue eptifibatide/tirofiban at

least 2–4 h before, and abciximab

≥12 h before CABG (Class I; LOE: B)

GP IIb/IIIa inhibitors

Anticoagulants

• Unfractionated heparin vs LMWH

– TIMI 11B, ESSENCE

• Bivalirudin

– ACUITY

• Fondaparinux

– OASIS-5

Moderate and high risk ACS

(n=13,819)

ACUITY: Study Design – First Randomization

An

gio

grap

hy

wit

hin

72

h

Aspirin in all Clopidogrel

dosing and timing per local practice

UFH/Enox + GP IIb/IIIa (n=4,603)

Bivalirudin + GP IIb/IIIa (n=4,604)

Bivalirudin Alone

(n=4,612)

R*

*Stratified by pre-angiography thienopyridine use or administration

Moderate and high risk unstable angina or NSTEMI

undergoing an invasive strategy (N = 13,819)

Medical management

PCI

CABG

Composite Ischemia – All pts

0

5

10

15

0 5 10 15 20 25 30 35

Cu

mu

lati

ve E

ven

ts (

%)

Days from Randomization

Estimate P (log rank) 7.4% UFH/Enoxaparin + IIb/IIIa (N=4603)

Bivalirudin + IIb/IIIa (N=4604) 0.37 7.9%

Bivalirudin alone (N=4612) 0.30 8.0%

UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone

Major Bleeding (Non CABG) – All pts

0

5

10

15

0 5 10 15 20 25 30 35

Cu

mu

lati

ve E

ven

ts (

%)

Days from Randomization

Estimate P (log rank) 5.7% UFH/Enoxaparin + IIb/IIIa (N=4603)

Bivalirudin + IIb/IIIa (N=4604) 0.41 5.3%

Bivalirudin alone (N=4612) <0.0001 3.1%

UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone

OASIS 5:

An International, Multicenter, Randomized, Double-Blind,

Double-Dummy Trial in 41 Countries

20,078 patients with UA/NSTEMI

Fondaparinux 2.5 mg s.c. od up to 8 days

Aspirin, Clopidogrel, anti-GPIIb/IIIa, planned

Cath/PCI as per local practice

Randomization

Enoxaparin 1 mg/kg s.c. bid for 2-8 days

1 mg/kg s.c. od if ClCr<30mL/min

1. Michelangelo OASIS 5 Steering Committee. Am Heart J 2005;150:1107.e1-.e10

2. OASIS 5 Investigators. N Engl J Med 1464-76

Vital status ascertained in 20,066 (99.9%) Lost to follow-up at day 9: fondaparinux: n=7 and enoxaparin: n=5

Death/MI/RI: Day 9

Days

Cu

mu

lati

ve

Ha

za

rd

0.0

0.0

10

.02

0.0

30

.04

0.0

50

.06

0 1 2 3 4 5 6 7 8 9

Enoxaparin

Fondaparinux

HR 1.01

95% CI 0.90-1.13

Major Bleeding: 9 Days

Days

Cu

mu

lati

ve

Ha

za

rd

0.0

0.0

10

.02

0.0

30

.04

0 1 2 3 4 5 6 7 8 9

HR 0.53

95% CI 0.45-0.62

P<<0.00001

Enoxaparin

Fondaparinux

ACS guidelines -Choose the right drugs and strategies before referal

ACS guidelines -Choose the right drugs and strategies ... · Assoc.Prof.Dilok Piyayotai Division of...

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Transcript of ACS guidelines -Choose the right drugs and strategies ... · Assoc.Prof.Dilok Piyayotai Division of...