1. The document discusses various treatment strategies for acute coronary syndromes (ACS), including ST-segment elevation myocardial infarction (STEMI) and non-STEMI.
2. Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for STEMI as it provides better outcomes than fibrinolytic therapy. However, fibrinolytics remain important when PCI is not accessible in a timely manner.
3. For non-STEMI ACS, an early invasive strategy with urgent catheterization and PCI improves long-term survival compared to a conservative approach. The optimal use of antiplatelet and anticoagulant therapies over time is also discussed.
Call Girls Service Noida Maya 9711199012 Independent Escort Service Noida
Intervention treatment for acs
1. Interventional Management of ACS
18th Myanmar Internal Medicine Conference 2017
Melia Hotal
29th September 2017
Prof Kyaw Soe Win
Mandalay General Hospital
2.
3. Spectrum of Pathologic and Clinical ST-Segment Elevation Acute Myocardial Infarction (STEMI)
and Non-STEMI Acute Coronary Syndromes.
Anderson JL, Morrow DA. N Engl J Med 2017;376:2053-2064
Spectrum of (STEMI)
and Non-STEMI
Acute Coronary
Syndromes.
4. STEMI
ACS Classification and Hospitalizations
Acute Coronary Syndromes
Unstable angina
TIMI flow grade 2/3
in culprit artery
NSTEMI
- Troponin + Troponin + Troponin
TIMI flow grade 0/1
in culprit artery
Gibson CM et al. Presented at: 2008 AHA Scientific Sessions. New Orleans, LA.
Go AS et al. Heart Disease and Stroke Statistics – 2013 update. Circulation. 2013;1127:e6-e245
0.81 million admissions per year 0.33 million admissions per year
Shared pathophysiology; Shared core treatment targets
Presentation
Emergency
Department
In-hospital
6-24hrs
5. Aim of Treatment for ACS
To re-establish the epicardial flow before irreversible
damage occurs:
• Pharmacological intervention
• Antiplatelets- oral/ parentral
• Anticoagulants
• Fibrinolytics
• Mechanical intervention
• Coronary Angiogram
• PCI
• CABG
6. Real World Interventional Cardiology Practice for CAD
Intervention treatment has prognostic benefit in STEMI and
High Risk NSTE-ACS
Optimal medical therapy is essential for stable CAD and low
risk NSTE-ACSintervention treatment has no prognostic
benefit
7. The important thing is Timing of intervention
•?Immediate
•?Early
•?Delayed
•?Elective
8. Acute STEMI
15 minutes 2 hours 6 hours
% necrosis 0% 50% 90%
Occlusive thrombus on a plaque of
atheroma
9. Goals in Reperfusion in Acute STEMI
Rapid
Complete - TIMI III - Epicardial artery
Integrity Of Microcirculation - Myocardial Perfusion
Sustained
“TIME IS MUSCLE!”
Thrombolytic
Therapy Primary PCI
13. Only 35% of 241,000 AMI pts were treated with lytics.
These lytic patients frequently needed other procedures:
70.7% underwent cath later before discharge
30.3% “ PTCA
13.3% “ CABG
LYTICS (35%) NO LYTICS (65%)
Mortality 5.9% 13.0%
Major bleeding 2.8% 0.5%
National Registry of Myocardial Infarction (NRMI)
14. Pooled data from 10 randomized trials (n=2,606):
Primary PCI is Superior to
Thrombolytic Therapy for Acute M.I.
Primary PTCA tPA p value
Mortality 4.4 % 6.5 % 0.02
Death or Reinfarction 7.2 % 11.9 % <0.001
Total Stroke 0.7 % 2.0 % 0.007
Hemorrhagic Stroke 0.1 % 1.1 % <0.001
Weaver, JAMA 1997;278:2093
15. Primary PCI is Superior to
Thrombolytic Therapy for Acute M.I.
pooled data from 21 randomized trials (n=7,739):
Primary PCI Lytic Rx p value
Mortality 6.9 % 9.3 % 0.0002
Reinfarction 2.4 % 6.8% <0.0001
Total Stroke 1.0 % 2.0 % 0.0004
Hemorrhagic Stroke 0.05 % 1.1 % <0.0001
Combined 8.2 14.3 <0.0001
Keeley, Lancet 2003;361:13-20
16. Primary PCI in Lytic Eligible Pts that are
High Risk (MITRA Registry)
(%)
O’Neill, J Invasive Cardiol 1998:10 Suppl A:4A-10A
High Risk Patients: Age >70, Anterior M.I., Heart Rate > 100
Death Reinfarction Death or Stroke
9.8%
6.7%
15.6%
3.6%
3.2%
1.4%
4.1%
0.5%
0
4
8
12
16 PCI Lytics
Death Reinfarction Death or Stroke
Re-MI
19. Can be used in virtually all infarct patients.
Produces TIMI-3 flow over 90% of the time, not 54%.
Does not cause intracranial bleeding.
Reduces need for subsequent procedures (cath, PCI).
Provides important angiographic information: patients who need
urgent surgery can be detected early.
Opens vessels as fast or faster.
Can improve prognosis in cardiogenic shock.
a five-fold reduction in mortality in high-risk STEMI pts compared to
thrombolytics.
Advantages of Primary PCI
20. Mortality rates with primary PCI as a function
of PCI-related time delay
P = 0.006
0 20 40 60 80 100
PCI-Related Time Delay (door-to-balloon - door-to-needle)
AbsoluteRiskDifferenceinDeath(%)
-5051015
Circle sizes = sample size of the
individual study.
Solid line = weighted meta-regression.
Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824-6
62 min Benefit
Favors PCI
Harm
Favors Lysis
21. Relationship Between Door-to-Balloon Time
Intervals and Mortality in NRMI
Cannon JAMA 2000
P = 0.35
P = 0.29
P = 0.01
P < 0.001
P < 0.001
0.6
0.8
1
1.2
1.4
1.6
1.8
2
2.2
0-60 61-90 91-120 121-150 151-180 > 180
Time (minutes)
Multvariate-adjustedOdds
ofIn-hospitalMortality
22. Challenges for STEMI system of care in Myanmar
• PCI is the GOLD standard, yet remains unaccessible to majority of patients.
• Primary PCI is available to <10% STEMI patients in Myanmar.
• 1.Lack of awareness
• 2.Lack of transfer facilities.
Unavailability of hospital with PCI facility.
• 3.Casualty/ED –to cath lab
Finance problem
Obtaining consent
Unavailability of cardiologist round the clock.
• Patient awareness and education for early symptom identification.
• Education required for General Practitioners /Physicians to implement early time dependent
STEMI management.
23. Total Ischemic Time 2013-2016
0
50
100
150
200
250
300
2013 2014 2015 2016
226.02 237.54
297.81
189.96
93.79 89.89
73.21
56.75
Patient delay System delay
01/19/2017 25How PPCI Program was started in Myanmar
24. Ischaemic time according to mode of admission (2016)
371
300
338
271
33 30
0
50
100
150
200
250
300
350
400
Through ERC Through Network
Total ischaemic time
Pain to CCU
Door to balloon
Note: Data including are describing the time in Minutes
25. Why it has to be stressed much regarding this approach ?
• Time is Myocardium.
• For each 30 min delay in treatment in STEMI patient,1 yr mortality increases by 7.5%.
• Mortality benefit with primary PCI is lost if PCI related delay exceeded 60 min.
Nallamothu et al ,Am J Cardiol,2004;94:772-774
• Practically, early fibrinolytic therapy can compensate for PCI related delay.
• Proportional mortality reduction was significantly higher in patients treated within 2 hrs
with fibrinolytics..
Circulation 2004;109:1223-1225
26. But… Fibrinolytics Still important
• Many patients present to hospitals without PCI capability
• Even so… PCI often cannot realistically occur within 90 minutes
• In NRMI 2006 Database, 27.6% of patients received fibrinolytic
therapy
Nallamothu BK, et al. Circulation 2005;111:761
Bates ER, et al. Circulation 2008;118:567
Antman EM, et al. JACC 2008;51:210
Gibson CM, et al. AHJ 2008;156:1035
27. How best to combine the two strategies?
• Can we improve on Primary PCI with concomitant (co-
administered) fibrinolytics?
• Immediate/Facilitated Approach
• Should all fibrinolytic patients go to PCI?
• Pharmacoinvasive approach
• Deferred approach
• Should only fibrinolytic “failures” get PCI?
• Rescue approach
29. Immediate/Facilitated PCI
• Definition: PCI immediately (< 3 hours) after fibrinolytics
• You may combine fibrinolytics with 2b/3a receptor inhibitors
• Theory:
Both PCI and Lytics
=
Rapid Early Reperfusion + Sustained Reperfusion
30. Immediate/Facilitated PCI
Why did it fail?
• Early period post-lytics (within 3 hours) carries the highest
risk of bleeding
• Early period paradoxically is also pro-thrombotic due to
degradation products
• Immediate PCI may increase bleeding and also paradoxically
increase ischaemic endpoints
• 2b/3a inhibitors may reduce the thrombotic complications
but at a cost of excess bleeding
41. Options for Reperfusion Therapy at Non-PCI
hospitals
Transfer for Primary PCI is better than…
Pharmaco-invasive strategy which is better than…
Fibrinolysis alone
42.
43.
44.
45.
46. What specific ACS strategies to NSTE-ACS
• Timing of invasive strategy? ASAP? Depending on risk group?
• Clopidogrel use: When? In Whom? How much?
• GPIIb/IIIa receptor antagonist: When? Upstream? At catheterization?
Routine? Provisional?
• Enoxaparin? Heparin? DTI(bivalirudin)? Xa inhibitor (Fondaparinux)?
47. Managing non-ST-segment elevation ACS by early
invasive therapy improves long-term survival and
reduces late myocardial infarction and
rehospitalization for unstable angina
Bavry AA, et al. J Am Coll Cardiol 2006;48:1319–1325
48. Invasive and Ischemia-Guided Intervention Categories in Patients with Non-STEMI Acute
Coronary Syndromes.
Anderson JL, Morrow DA. N Engl J Med 2017;376:2053-2064
49. 1. The concept of “risk” in the STEMI and NSTE-ACS patient
applies only to ischemic events.
2. For primary PCI, it is all about door-to-balloon time:
Antithrombin therapy doesn’t matter….
50. • Recurrent ischemic events are associated with worse survival.
• This is true for patients with ACS and those undergoing PCI.
BUT…
• The risk appears limited to the 30 days after the index event.
• What about the bleeding events?
51. SYNERGY
LMWH
ESSENCE
1994 1995 1996 1997 1998 1999 2000 2002 2003 2004 2005 20062001
CURE
Clopidogrel
Bleeding risk
Ischemic risk
GP IIb/IIIa
blockers
PRISM-PLUS
PURSUIT
ACUITYTACTICS TIMI-18
Early invasive
PCI ~ 5% stents ~85% stents Drug-eluting stents
ISAR-REACT 2
Milestones in ACS Management
OASIS-5
[ Fondaparinux ]
Anti-Thrombin Rx
Anti-Platelet Rx
Treatment Strategy
Heparin
Aspirin
Conservative
ICTUS
Bivalirudin
REPLACE 2
Adapted from and with the courtesy of Steven Manoukian, MD.
52. 1992 1995 1998 2001 2004 2007
1997 1999
UFH
LMWH TIMI 11B
2004
SYNERGY
Bivalirudin
2003
REPLACE 2
ASA
IIb/IIIa
antagonists
1995
2001
1998
EPISTENT
PURSUIT
2001
ESPRIT
GUSTO 4
2004
ISAR REACT
Clopidogrel CURE
2000
Anti-thrombotic agents
Anti-platelet agents
Evolving ACS Therapies and Patterns of Antithrombotic Use*
ACUITY
2006
ISAR-REACT 2
* Width of bar represents approximate degree of use of antiplatelet or anticoagulants at a particular time
53. • Clinical trials with GP IIb/IIIa inhibitors show reductions in recurrent
ischemic events in risk-stratified subsets when they are added to
unfractionated heparin.
BUT…
• Bleeding risks are clearly higher with GPI.
• GPIs have never been shown to improve survival in the modern era of
PCI or ACS management.
• A strategy of bivalirudin appears at least as good as UFH + GPI in the
ACS patients across the entire risk spectrum.
54. • Major bleeding (with or without blood product
transfusions) has emerged as a powerful
independent predictor of early and late mortality in
pts with NSTEMI, STEMI and in those undergoing PCI
55. Time from Randomization in Days
Cumulative%Mortality
With MI 5.7%
Without major bleed 2.0%
Impact of Major Bleed and MI
after Elective and Urgent PCI
1-Year Mortality (N=6,012)
Without MI 1.9%
With major bleed 8.8%
Stone GW. J Inv Cardiol 2004;16(suppl G):12–17.
56. Variable Groups O.R. (95% CI) p-value
Creatinine clear. <30 mL/min 7.21 (2.53–20.51)
<0.000130–60 mL/min 3.34 (1.92–5.78)
60–90 mL/min 1.57 (0.96–2.57)
CHF Yes 4.38 (2.83–6.78) <0.0001
Major Bleeding Yes 3.26 (1.78–5.96) 0.0001
MI @30day Yes 2.77 (1.62–4.75) 0.0002
Urg Revasc @30d Yes 2.77 (1.15–6.71) .024
Hx angina Yes 2.18 (1.25–3.81) 0.006
Prior MI Yes 1.81 (1.09–3.03) 0.023
Diabetes Yes 1.64 (1.10–2.44) 0.015
Predictors of 1-year Mortality
after Elective and Urgent PCI
Stone GW. J Inv Cardiol 2004;16(suppl G):12–17.
57. Mehran RM et al. In press EHJ
Influence of Major Bleeding and MI in the First 30 Days on
Risk of Death Over 1 Year
Cox model adjusted for 36 baseline predictors, with MI and major bleeding
(non-CABG) as time-updated covariates
Of 13,819 enrolled pts, 524 (3.8%) died within 1 year
Myocardial infarction 2.51 (1.95-3.25) <0.0001
Major bleeding without or before
transfusion 2.00 (1.30-3.06) <0.0001
Major bleeding after transfusion 3.93 (2.95-5.24) <0.0001
HR ± 95% CI P-valueHR (95% CI)
58. Mehran RM et al. In press EHJ
Influence of Major Bleeding and MI in the First 30 Days on
Risk of Death Over 1 Year
Cox model adjusted for 36 baseline predictors, with MI and major bleeding
(non-CABG) as time-updated covariates
Of 13,819 enrolled pts, 524 (3.8%) died within 1 year
Myocardial infarction 2.51 (1.95-3.25) <0.0001
Major bleeding without or before
transfusion 2.00 (1.30-3.06) <0.0001
Major bleeding after transfusion 3.93 (2.95-5.24) <0.0001
HR ± 95% CI P-valueHR (95% CI)
Attributable
deaths
51.5*
66.5**
Attributable deaths = N deaths
among pts with the time updated
event (attribute) X (adj. HR – 1)/adj. HR
*9.8% of all deaths
**12.7% of all deaths
59. HR (95% CI) P-value
Attributable
deaths
MI Day 0-1 17.6 (10.8 to 28.7) <0.001 21
Days 2-7 8.2 (5.0 to 13.6) <0.001 19
Days 8-30 2.9 (1.6 to 5.3) 0.001 12
Days 31+ 1.4 (0.9 to 2.1) 0.12 25
Major bleed Day 0-1 5.5 (2.7 to 11.0) <0.001 9
(non CABG) Days 2-7 5.8 (3.5 to 9.7) <0.001 18
Days 8-30 5.6 (3.5 to 8.8) <0.001 24
Days 31+ 2.4 (1.7 to 3.3) <0.001 42
Transfusion Day 0-1 6.7 (3.1 to 14.7) <0.001 7
Days 2-7 8.1 (4.6 to 14.1) <0.001 15
Days 8-30 6.4 (3.7 to 10.9) <0.001 17
Days 31+ 3.1 (2.1 to 4.5) <0.001 31
Influence of MI, Major Bleed and Transfusion in the First 30 Days
on the Risk of Death Over 1 Year
Mehran RM et al. In press EHJ
0.5 1 2 4 8 16 32
Hazard ratio (95% CI)
Attributable deaths = N deaths
among pts with the time updated
event (attribute) X (adj. HR – 1)/adj. HR
61. Considerations in the Modern Era of ACS/PCI
• 55-year-old male with 3 hours
of chest pain
●Hx of HTN, lipids
●Marked ST-segment
depression leads II, III, aVL
●Elevated serum troponin T,
CKMB 4 X ULN
●Normal renal function
• 86-year-old female with 3 hours
of chest pain
●Hx of DM, HTN, lipids
●ECG non-specific (no prior
study for comparison)
●Elevated troponin, normal
CKMB
●Est. GFR 45 ml/min
62. ACS-related Bleeding—Relevant Questions
• Who bleeds? Can we risk stratify?
• Should bleeding risk affect upstream antithrombotic care? If so, how?
• Is bleeding bad or a necessary evil?
• Can blood transfusion “correct” risks associated with bleeding?
• Does bleeding affect resource use?
63. Independent
predictors of
major bleeding
in marker- positive
acute coronary
syndromes
Moscucci, GRACE Registry, Eur Heart J. 2003 Oct;24(20):1815-23.
Predictors of Major Bleeding in ACS
• Older Age
• Female Gender
• Renal Failure
• History of Bleeding
• Right Heart Catheterization
• GPIIb-IIIa Antagonists
64. 26,452 patients from PURSUIT, PARAGON A, PARAGON B, GUSTO IIb NST
Bleeding severity and adjusted hazard of death
*p<0.0001
Bleeding and Outcomes in NSTE-ACS
Rao SV, et al. Am J Cardiol. 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12.
Bleeding Severity 30d Death 30d Death/MI 6 mo. Death
Mild* 1.6 1.3 1.4
Moderate* 2.7 3.3 2.1
Severe* 10.6 5.6 7.5
*Bleeding as a time-dependent covariate
65. • Bleeding is associated with adverse short- and long-term outcomes
among patients with ACS and those undergoing PCI
● Mortality rates are higher among those who bleed
● MI rates are higher among those who bleed
• Worse bleeding associated with worse outcomes
• This relationship is persistent after robust statistical adjustment for
confounders
Bleeding and Outcomes in ACS
66. 30-Day Survival By Transfusion Group
Rao SV, et. al., JAMA 2004;292:1555–1562.
Transfusion in ACS
N=24,111
30-Day Survival By Transfusion Group
67. • Blood transfusion is independently associated with worse short
and long-term outcomes including death and recurrent MI
• Transfusion does not correct the adverse impact bleeding and is
associated with increased mortality in ACS patients
• Blood transfusion is best avoided in ACS patients whenever
possible and is associated with increased mortality in ACS
patients
Blood Transfusion in ACS
68. Bleeding Among Patients with ACS
• There are several therapeutic pathways for ACS care
• Choices for therapy must take into account:
● Ischemic complications
● Bleeding complications
• The risk for bleeding and ischemia increases from NSTE-ACS to STEMI
69. White HD et al. JACC 2008;51:1734-41.
Switching in ACUITY
70. Reducing (re)MI—Effect on mortality
Therapy Reduces mortality?
Clopidogrel Modestly in STEMI
GP IIb/IIIa No
UFH No
Enoxaparin No
Yusuf S. et. al. NEJM 2001
Boersma E. et. al Lancet 2002
SYNERGY Investigators. JAMA 2004
71. Switching Antithrombins: A Practical Strategy for the ACS Network
SYNERGY ACUITY UVM Registry
Antithrombin comparison Enoxaparin vs. UFH
UFH/Enoxaparin vs.
Bivalirudin
UFH/Enoxaparin vs.
Bivalirudin
N 9978 7104 728
Pre-randomization
antithrombin treatment
76% 59% 44%
Switch (%) 35% 29% 44%
Consistent Therapy vs.
Switched (%)
Does Not Favor
Switching
Favors
Switching
Neutral
Death or MI 14.2% vs. 22.0%* 7.4% vs. 6.9% 8% vs. 7%
Bleeding 15.1 % vs. 35.1* 5.8% vs. 2.8%+ 2% vs. 2%^
73. Ischemic
Complications
Hemorrhage
HIT
► Death
► MI
► Urgent TVR
► Major Bleeding
► Minor Bleeding
► Thrombocytopenia
Composite Adverse Event Endpoints
Evolving Paradigm for Evaluating
ACS Management Strategies
74. Periprocedural
Complications
Clinical
Benefit
► Death
► Major Disability
► Cost
► Ease of Use
► Duration of
Therapy
► Accounting for
Bleeding and
Ischemic
Endpoints
Composite Adverse Event Endpoints
Evolving Paradigm for Evaluating ACS
Management Strategies
75. • a balance must be struck between ischemia reduction and bleeding.
• Both ischemic complications and bleeding are associated with increased
costs.
76. • Escalation of therapy for ischemia in this setting is associated with increased risk
of bleeding
• This “price to be paid” has generally been accepted and tolerated, especially in
patients at high ischemic risk, who benefit disproportionately from advanced
therapy
• Enox superior to UFH in patients with higher TIMI Risk Scores
• Clopidogrel + ASA superior to ASA alone in patients with higher TIMI Risk Scores
• GP IIb/IIIa receptor antagonists benefit troponin positive patients more than troponin
negative patients
77. Changing the Calculations for
Assessing Guidelines Adherence
Anderson HV, Bach RG, J Am Coll Cardiol 2005;46:1488-9.
“We need to invert the current equation to calculate an opportunity score for
ACS patients rather than a risk score. Patients with higher baseline risks, such as
the elderly, would have higher opportunity scores for benefit, even allowing for
some of the greater risks from the treatment.”
78. Balancing Efficacy and Safety
• Current guidelines emphasize reduction of ischemic risk in NSTE ACS—
especially for upstream therapy
• Updated guidelines are expected to include data on the harm that
bleeding events cause, diminishing ischemic efficacy in some patients
• Most of physicians are comfortable with the goal of reducing ischemic
risk . . . and traditionally have left concern over bleeding to “downstream
providers”
• “balanced” pharmacotherapy will require multidisciplinary
collaboration, pathways, anticipation of consistent care (especially time
from ED to cath), and individualized patient assessment
81. What have we learned and what can be done to
improve the process of PPCI?
1. Patients’ delays: Public awareness of heart attacks
2. System Delays:
1. Late Arrival in the ER
2. Delay in the diagnosis at ER
3. Delay in the referral to CCU
01/19/2017 83How PPCI Program was started in Myanmar
• single call activation to engage the cath lab
• Bypass the ER
• Develop prehospital alert and ECG transmission
using Smartphone applications and cathlab
activation before patient arrived to CCU
• avoid delay to activate the team outside working
hours
• complete coverage for PPCI irrespective of the
financial status
82. 1st March 2015
MGH STEMI Network laughed on the day
of celebration of second year anniversary
of PPCI and Heart Attack Awareness Week
Key To Improving STEMI Care: STEMI network
01/19/2017 84How PPCI Program was started in Myanmar
89. ERC
ER MGH
x
xCall us and send ECG by Viber
09-259898661
09-259898662
01/19/2017 91How PPCI Program was started in Myanmar
90. Total Ischemic Time 2013-2016
0
50
100
150
200
250
300
2013 2014 2015 2016
226.02 237.54
297.81
189.96
93.79 89.89
73.21
56.75
Patient delay System delay
01/19/2017 92How PPCI Program was started in Myanmar
91. Ischaemic time according to mode of admission (2016)
371
300
338
271
33 30
0
50
100
150
200
250
300
350
400
Through ERC Through Network
Total ischaemic time
Pain to CCU
Door to balloon
Note: Data including are describing the time in Minutes