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Slide materi webinar 28 juni 2020
1. Patient First,
PCI is Feasible and Reasonable for
STEMI Patients During The
COVID-19 Pandemic in Malang
Mohammad Saifur Rohman1,2
1Department of Cardiology and Vascular Medicine, Faculty of
Medicine, Brawijaya University/dr. Saiful Anwar Hospital, Malang
2Brawijaya Cardiovascular Research Centre
4. Where The Fibrinolysis Take Place ?
ā¢ Fibrinolytic therapy is reperfusion strategy in settings where primary PCI
cannot be offered in a timely manner. The largest absolute benefit is
offered <2 h after symptom onset if primary PCI can not be performed
within 120 min from STEMI diagnosis and there are no
contraindications.
ā¢ In a meta-analysis of six randomized trials pre-hospital fibrinolysis
reduced early mortality by 17% compared with in-hospital fibrinolysis,
particularly when administered in the first 2 h of symptom onset.
ā¢ The later the patient presents (particularly after 3 h) the more
consideration should be given to transfer for primary PCI (as opposed to
administering fibrinolytic therapy) because the efficacy and clinical
benefit of fibrinolysis decrease as the time from symptom onset
increases.
2017 ESC guideline
Malang ?
5. RS dr Saiful Anwar: 6.32 Ā± 5.37 hours
RS Harapan Kita: 5.78 Ā± 5.2 hours
2004. Guidelines for the management of patients with STEMI
Prehospital delay in 2 diff city
2004
2011
6. Delay Treatment of AMI Patients in Malang
AMI
Patients
Saiful
Anwar
Hospital
9.5%
Self
medication
56%
Health
provider
4. 35Ā±2.77 hours
4.08Ā±4.63 hours
7.68Ā±5.43 hours
5.33Ā±2.78 hours
50% aware
16.7% aware
34.3% aware
70 % aware
Rohman MS, Dwi Chya, Rahmawatus, Mefetika, Prsented at ASMIHA 2012
PCI is Better Applied in Malang, since chest pain onset > 2 hours at the presentation
7. PCI+ACS Network Reduced All Cause Mortality in
RSSA
Clinical
Research
Problem
Solving : ACS
Network
MONEV
Feedback/follow
up stakeholder Education
Training/Workshop
Optimize The System ;
Drugs, tools etc.
In hospital mortality 20.1% (2011) 9.4% (2015)
Rohman MS, et al. 2016
PROVEN !
8. PCI More Superior than Fibrinolytic
ā¢ Primary PCI is the preferred reperfusion therapy for acute
STEMI
ā¢ Superior Efficacy (over 90% restoration of TIMI 3 flow)
ā¢ Superior Safety (less stroke / bleeding)
ā¢ Superior Long term outcomes (less reinfaction / restenosis)
ā¢ Less impacted by patient related factors (symptom onset, etc)
ā¢ Better outcomes for high risk patients
PCI during COVID -19 pandemic?
9. ManagementofAcuteMyocardialInfarction
DuringtheCOVID-19 Pandemic
A Consensus Statement from the Society for Cardiovascular Angiography and
Interventions (SCAI), American College of Cardiology (ACC), and the American
College of Emergency Physicians (ACEP)
Ehtisham Mahmud, MD FACC FSCAI1*
Harold L Dauerman, MD FACC FSCAI2
Frederick GP Welt, MD FACC FSCAI3Ā§
John C. Messenger, MD FACC FSCAI4*
Sunil V. Rao, MD FACC FSCAI5*
Cindy Grines, MD FACC MSCAI6*
Amal Mattu, MD FACEP7ā”
Ajay J. Kirtane, MD SM FACC FSCAI8Ā§
Rajiv Jauhar, MD FACC FSCAI9
Perwaiz Meraj, MD FACC FSCAI10
Ivan C. Rokos, MD FACEP11
John S. Rumsfeld, MD PhD FACC12Ā§
Timothy D Henry, MD FACC MSCAI13*Ā§
Ā§ Representative of the American College of Cardiology
ā” Representative of the American College of Emergency Physicians
* Representative of the Society of Cardiovascular Angiography & Interventions
Author Affiliations
1 University of California, SanDiego,SulpizioCardiovascularCenter, LaJollaCA;2 Universityof Vermont,
BurlingtonVT;3 University of Utah Medical Center, SaltLake CityUT; 4 Universityof ColoradoSchool of
Medicine, AuroraCO;5 Duke University Hospital, DurhamNC;6 Northside CardiovascularInstitute,
AtlantaGA; 7 Universityof MarylandSchool of Medicine,Baltimore MD;8 ColumbiaUniversity Medical
Center,CenterforInterventional VascularTherapy, New YorkNY;9 Northwell Health, ManhassetNY;10
14. Mrs E, A smoker 62 year old woman, Presented to ER with chief complaint of Chest pain.
Patient suffered from heavy like sensation chest pain radiated to the jaw 30 minute
prior to admission. Vas 8/10 pain has happen after she climb 2 level of stairs and
hadnāt relieved by taking a rest for more than 30 minutes. The pain accompanied
with cold sweating.
Her family than brought her to non capable PCI private hospital. She was diagnosed
with STEMI infero-posterior with shock and given loading 320mg of aspilet, 180
mg of ticagleror, loading NS 0.9% of 500 ml with maintenance 1cc/kg/hour,
dobutamine 5mcg/kg/min and referred to RSSA (nearest PCI capable hospital for
PPCI.
Past history and risk factors:
Patient confessed previous heart attack 10 years since then she never visited to out
patient clinic.
History of DM and hypertension were denied. She was menopause for 10 years
Family History of CAD: Her father cardiac death <55 yo.
Case 1
15. OBJECTIVES
Physical Examination :
General appearance look moderately ill
GCS : E4M6V5
BP : 153/99 mmHg on Dobutamine
5mcg/kgBB/min
PR : 88 bpm Strong, regular
RR : 18 tpm
SpO2 98% on NC 4 lpm
Tax: 36,5
Head and Neck :
Conj. pale -|-; Icteric sclera -|-
JVP R+0 cmH2O
Pupil isokor 3mm/3mm
OBJECTIVES
Thorax :
Cor: ictus cordis invisible, palpable at
ICS V MCL sin
S1 S2 regular, murmur (-), gallop (-)
Pulmo: v v Rh - - Wh - -
v v - - - -
v v - - - -
Abdomen : flat, soefl, bowel sound (+)
N
Extremities : leg swelling -|-,
warm acrals, CRT 2 seconds
UOP 400 ml/3 hours
25. Condition After PPCI
ā¢ S: Chest pain subsided VAS 0/10
ā¢ O:
ā¢ BP 111/72 mmHg
ā¢ HR 71 bpm
ā¢ RR 18 x/min
ā¢ Tax; 36.5 C
ā¢ SpO2 98% NC 4 lpm
ā¢ Urine output 1500 ml/18h
ā¢ Balance -382 ml/18h
A : Infero-posterior STEMI Killip IV
CAD 3 VD post PCI 1 DES in RCA
P: Echo
Aspilet 80mg 1x1
Ticagleror 90mg 2x1
Nitrat 5 mg 3x1
Ramipril 5 mg 1x1
Atorvastatin 40 1x1
GPIIb/IIIa or heparin for 48 hours
26. Mr J, 43 year old ex smoker male presented to ER with chest pain
Patient suffered from progressive heavy-like sensation chest pain 8
hours prior to admission, The VAS 9/10 pain was occurred at rest
for more than 30 minutes. The chest pain was radiated to the back,
left shoulder, and neck, accompanied with cold sweating, and
vomiting. He was brought to the nearest non capable PCI hospital
and diagnosed with anterior STEMI. 320mg of aspilet and 300mg
of clopidogrel, and drip ISDN 1mg/hour then he was referred to
RSSA for further management.
At ER RSSA, chest pain still persisted with VAS 6/10 on drip ISDN 1
mg/hour. Patient, therefore, was treated with Fibrinolytic but it was
failed and planned for rescue PCI
Past history and risk factor : Ex-smoker was quit since 10 years ago
Case 2
38. Dual-antiplatelet therapy (DAPT)
after PCI in patients with acute
coronary syndromes might
sometimes be shortened to as
little as 3 months using a
polymer drug-eluting stent (DES)
loaded with sirolimus and an
endothelium-promoting
antibody
COMBO DES
40. Condition After PPCI
ā¢ S: Chest pain - , dyspnea -
ā¢ O:
ā¢ BP 138/68 mmHg
ā¢ HR 80 bpm
ā¢ RR 20 x/min
ā¢ Tax 37 C
ā¢ SpO2 % 99 NC 4 lpm
ā¢ Urine output 1700 ml/12h
A : Anterior STEMI Killip I
CAD 2 VD post rescue PCI 1 DES in LAD
P: Echo
Aspilet 80mg 1x1
Ticagleror 90mg 2x1
Nitrat 5 mg 3x1
Ramipril 10 mg 1x1
Atorvastatin 40 1x1
GPIIb/IIIa or heparin for 48 hours
41. Conclusion
ā¢ PCI is the standard of care for patients presenting to
PCI centers. This should remain the standard of care
for STEMI patients during the COVID-19 pandemic
with some important caveats
ā¢ PCI Is Feasible and Reasonable for STEMI Patients
During The COVID-19 Pandemic in Malang
42. Thank you
Acknowledgment:
To All Cath. Lab members
CVC ward members
Dr Saiful Anwar hospital staffs
Allah Berfirman: āDan barangsiapa yang memelihara kehidupan seorang manusia, maka
seolah-olah dia telah memelihara kehidupan manusia semuanya.ā (QS. Al Maidah: 32)
Dari Abu Hurairah Radhiyallahu anhu , Nabi Shallallahu āalaihi wa sallam bersabda,
āBarangsiapa yang melapangkan satu kesusahan dunia dari seorang Mukmin, maka AllĆ¢h
melapangkan darinya satu kesusahan di hari Kiamat. Barangsiapa memudahkan orang
yang kesulitan, maka AllĆ¢h Azza wa Jalla memudahkan baginya (dari kesulitan) di dunia
dan akhirat. Barangsiapa menutupi (aib) seorang Muslim, maka AllĆ¢h akan menutup
(aib)nya di dunia dan akhirat. AllĆ¢h senantiasa menolong seorang hamba selama hamba
tersebut menolong saudaranya. ā¦ā¦.ā HR riwayat muslim, abu dawud, thirmidzi dan
lainnya.
43. Trombolysis as the best alternative
treatment
for STEMI revascularisation
procedure
during COVID-19 Pandemic Era
dr. Sasmojo Widito, SpJP(K)
Malang
Juni 2020
44. Abbreviation
ā¢ ACE : angiotensin converting enzyme
ā¢ CCL : cardiac catheterization laboratory
ā¢ CV : cardiovascular
ā¢ DBP : Diastolic Blood Pressure
ā¢ ECD : emergency cardiology department
ā¢ FT : Fibrinolytic therapy
ā¢ IRA : infarct related artery
ā¢ PCI : percutaneous coronary intervention
ā¢ PI : pharmacoinvasive strategy
ā¢ PPE : personal protective equipment
ā¢ PUI : person under investigation
ā¢ SBP : Systolic Blood Pressure
ā¢ STE : ST-elevation
ā¢ STEMI : ST-elevation myocardial infarction
45. On January 30, 2020, the World Health
Organization declared COVID-19, the
disease caused by the novel
coronavirus, a public health
emergency of international concern
and later officially upgraded it to a
global pandemic.
INTRODUCT
ION
According data from The
Indonesian COVID-19
task force , On June 20, 2020,
more than 45029 confirmed cases
in Indonesia and more than 2429
deaths have been documented.
Coronary heart disease is
present in 38% and diabetes in
19% of COVID-19 patients. A
report on 136 Covid-19 patients
shows that 26% of them
required cardiovascular
intensive care. They had a
higher rate of death and a
01
03
02
2
Roser M, Ritchie H, Ortiz-Ospina E, Hasell J. Coronavirus Pandemic (COVID-19). Our
World in Data. 2020 May 26.
Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta bio-medica: Atenei
Parmensis. 2020 Mar 19;91(1):157-60.
Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, Jain SS, Burkhoff
D, Kumaraiah D, Rabbani L, Schwartz A. COVID-19 and cardiovascular disease.
Circulation. 2020 May 19;141(20):1648-55.
46. the pandemic had spread to all 34 provinces. The largest increase of new cases in a single
day occurred on 10 June, when 1,241 cases were announced. On 14 June, for the first time
ever, there were more than 750 recoveries recorded just within a span of 24 hours. As of 17
June, Indonesia has reported 41,431 cases, the highest in Southeast Asia.
Cases per million by province as of 20 June 2020
Confirmed cases by province as of 20 June 2020
Deaths by province as of 20 June 2020
Recoveries by province as of 20 June 2020
3
Indonesianās COVID-19 (Task Force) Acceleration Countermeasures Group, June 20, 2
48. INCREASE MORTALITY IN COVID 19 WITH
CARDIOVASCULAR COMORBIDITY
Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, Wang H, Wan J, Wang X, Lu Z. Cardiovascular implications of
fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA cardiology. 2020 Mar 27. 5
49. Corona Virus Disease 2019
(COVID-19) caused by severe
acute respiratory syndrome
coronavirus 2 (SARS-CoV-2
virus), occurs in addition to
existing challenges to
emergency services,
like ST-elevation myocardial
infarction (STEMI).
Both conditions may coexist,
initial
presentations can overlap, and
true and reliable point-of-care
testing does not exist.
Symptoms alone are unhelpful,
as most screened for COVID-19
test negative (30% can be false
negative) and ā80% of COVID-19
infections are asymptomatic.
Wood S. The Mystery of the Missing STEMIs During the COVID-19 Pandemic. tctMD. April 2, 2020.
POSTPONED
----------------
Regarding the
healthcare
system and in
order to focus
on the
management
of COVID-19
incoming
patients, all
elective
procedures in
hospitals
were
postponed
DELAY >12
HOURS
-------------------
in which
symptoms of
acute
coronary
events are
usually less
specific, a
delay in
diagnosis and
lack of the
appropriate
treatment,
can lead to
rapid
deterioration,
URGENT
--------------------Only
the urgent ones
were permitted.
However, the
recommendation
s to avoid
hospital visits,
together with the
fear of getting
infected by
COVID-19, may
have forced
individuals to
underestimate
the symptoms of
a disease onset,
and, therefore, to
delay the
diagnosis of
various,
especially acute
6
Gupta AK, Jneid H, Addison D, Ardehali H, Boehme AK, Borgaonkar
S, Boulestreau R, Clerkin K, Delarche N, DeVon HA, Grumbach IM.
Current perspectives on Coronavirus 2019 (COVIDā19) and
cardiovascular disease: A white paper by the JAHA editors. Journal
50. Tsioufis K, Chrysohoou C, Kariori M, Leontsinis I, Dalakouras I, Papanikolaou A, Charalambus G, Sambatakou H, Siassos G, Panagiotakos D, Tousoulis D. The mystery of āmissingā visits in an emergency cardiology
department, in the era of COVID-19.; a time-series analysis in a tertiary Greek General Hospital. Clinical Research in Cardiology. 2020 Jun 6:1.
7
51. COVID-19 is primarily a respiratory
disease, but many patients also
have CVD, including hypertension,
acute cardiac injury and myocarditis
This may be secondary to the lung
disease, since acute lung injury itself
leads to increased cardiac workload
and can be problematic especially in
patients with pre-existing HF.
CVD may also be a primary
phenomenon considering the
important (patho)physiological role
of the RAS/ACE2 in the CV system.
ACE2 is also expressed in human
heart, vascular cells and pericytes.
Kuster GM, Pfister O, Burkard T, Zhou Q, Twerenbold R, Haaf P, Widmer AF, Osswald S. SARS-CoV2: should inhibitors of the renināangiotensin system be withdrawn in patients with COVID-19?. European
Heart Journal. 2020 Mar 20.
8
52. STEMI Revascularisation Procedure during COVID-19
era
in Saiful Anwar Teaching Hospital Malang
PCI
LOREM
IPSUM
LOREM
IPSUM
Fibri
lolys
is
PCI
LOREM
IPSUM
LOREM
IPSUM
Fibri
noly
sis
78
%
12
%
27
%
52
%
Mean of the total patient
from january-february
34.5/month
Majority of this patients
performed PPCI
Mean of the total patient
from March-May
26.3/month
Majority of this patients
performed fibrinolytic
9
54. FIBRINOLITYC THERAPHY (FT) VS
PCI
Experts dealing
with the COVID-19
epidemic in China
recommend
fibrinolytic therapy
(FT) over primary
percutaneous
coronary
intervention (PPCI)
for STEMI.
FT was the first
effective reperfusion
treatment to be
systematically
implemented
for STEMI.
STREAM (Strategic Reperfusion Early
After Myocardial Infarction) ļ STEMI
patients ā¤3 hours of symptom onset,
who were unable to access PPCI ā¤1 hour
of first medical contact. Patients were
randomized to FT, or PPCI
When delays in PPCI are unavoidable, a
pharmacoinvasive approach is not worse
than PPCI in the P2Y12 inhibitor era.
0
2
0
1
03
04
05
Outcomes of FT versus PPCI
were similar (death, shock,
heart failure, or reinfarction)
Need for emergent
angiography in the fibrinolytic
arm was 36%; mortality was <5%
in both groups. Intracranial
hemorrhage was higher with FT
(1.0% vs 0.5%, P=0.02).
11
Bainey KR, Bates ER, Armstrong PW. STEMI Care and COVID-19: The Value Proposition of Pharmacoinvasive Therapy. Circulation:
55. PPCI relies heavily on
systems of care, not
just individual
operators.
PPCI treatment delays
in the COVID-19 era
arise, even among
COVID-19 negative
Patients
Caused of Delay
> the steps and time in
the emergency room
required to establish
contact history,
symptomatology,
chest x-ray, etc, before
transfer to the cardiac
catheterization
laboratory (CCL).
> CCL staff require
time
PCI DELAY
Bainey KR, Bates ER, Armstrong PW. STEMI Care and COVID-19: The Value
Proposition of Pharmacoinvasive Therapy. Circulation: Cardiovascular Quality and
12
56. Early reperfusion may be
more important than the
mode of reperfusion.
EUGINE BRAUNWALD, 2016
In this setting, immediate fibrinolytic administration in the emergency department
may mitigate systems-based delays. A door-to-needle time of 30 minutes may be
more achievable
than a door-to-balloon time of 90 minutes.
Braunwald E, Rutherford JD. Limitation of infarct size and the open artery hypothesis: a conversation with
Eugene Braunwald, MD. Circulation. 2016 Sep 20;134(12):839-46.
57. 0
4
03
0
2
01
REASON: Fibrinolytic VS PCI during Covid-19
pandemic
RESOURCES
During this Covid-
19 outbreak,
Hospitals face an
unfamiliar
conditions, and
limited resources,
namely:
> Protective
Equipment.
> Medical staff
> Competence of
medical staff
> needs of
equipment, and
device
In Patients with
STEMI and
COVID-19, the
shorter length of
stay promised by
PPCI is negated
by the time
required to treat
hospitalized
COVID-19
infections.
Patients initially
treated with FT
could complete
their
when considering
the implications
of the Covid-19
outbreak in
hospital human
resources,
equipment
resources, and
financial support,
fibrinolytic
therapy is a
rational choice.
Some patients
more
appropriate for
FT than others.
Patients without
extensive infarcts
who
present early (<3
hours) may be
well-suited for
FT.
With careful
monitoring and
consideration for
rescue PCI in case
of failed
Bainey KR, Bates ER, Armstrong PW. STEMI Care and COVID-19: The Value Proposition of Pharmacoinvasive Therapy. Circulation: Cardiovascular Quality and Outcomes. 2020 Apr 27.
14
58. European Society of Cardiology. ESC guidance for the diagnosis and management of CV disease during the
COVID-19 pandemic. ESC. 2020.
20
59.
60. Relative association of continuous PCI-
related delay and study treatment with
primary endpoint
p
(interaction)=0.
073
Gershlick AH et al. Heart
1-Jul-20 Webinar Perki Malang
63. Ibanez, B., James, S., Agewall, S., Antunes, M.J., Bucciarelli-Ducci, C., Bueno, H., Caforio, A.L., Crea, F., Goudevenos, J.A., Halvorsen, S. and
Hindricks, G., 2018. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment
elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the
European Society of Cardiology (ESC). European heart journal, 39(2), pp.119-177.
23
STEMI Revascularisation Procedure
Choices
Fibrinolityc vs Primary PCI
1-Jul-20 Webinar Perki Malang
65. STEMI Revascularisation
Procedure Choices
Clinical success of Fibrinolysis therapy
Webinar Perki Malang
1-Jul-20
European Heart Journal (2018) 39, 119ā177
Clinical success of fibrinolysis therapy:
ā¢ disappearance of chest pain
ā¢ ST-segment resolution > 50% at 60ā90min;
ā¢ typical reperfusion arrhythmia;
Early angiography with subsequent PCI if indicated is also the
recommended standard of care after successful fibrinolysis
procedure, if there are no contraindications
66. Ibanez, B., James, S., Agewall, S., Antunes, M.J., Bucciarelli-Ducci, C., Bueno, H., Caforio, A.L., Crea, F., Goudevenos, J.A., Halvorsen, S. and
Hindricks, G., 2018. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment
elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the
European Society of Cardiology (ESC). European heart journal, 39(2), pp.119-177.
24
STEMI Revascularisation Procedure
Choices
Doses of Fibrinolytic therapy
1-Jul-20 Webinar Perki Malang
67. 26
The illustration of the fibrinolytic mechanisms: (a)
tissue plasminogen activator (tPA) causes breakdown
of the clot, and (b) detailed mechanism of
fibrinolysis. Green arrow denotes
activation/stimulation, and the red arrow indicates
inhibition. tPAā=ātissue plasminogen activator;
Bhaskar S, Stanwell P, Cordato D, Attia J, Levi C.
Reperfusion therapy in acute ischemic stroke:
dawn of a new era?. BMC neurology. 2018
69. 1-Jul-20 Webinar Perki Malang
International Journal of Cardiovascular Sciences. 2020; 33(3):288-294
Safety recommendations for CCL procedures during
the COVID-19 pandemic
70. 1-Jul-20 Webinar Perki Malang
International Journal of Cardiovascular Sciences. 2020; 33(3):288-294
Safety recommendations for CCL procedures during
the COVID-19 pandemic
71. 1-Jul-20 Webinar Perki Malang
International Journal of Cardiovascular Sciences. 2020; 33(3):288-294
Safety recommendations for CCL procedures during
the COVID-19 pandemic
72. 1-Jul-20 Webinar Perki Malang
Safety recommendations for CCL procedures during
the COVID-19 pandemic
International Journal of Cardiovascular Sciences. 2020; 33(3):288-294
73. The Role of Eptifibatide in
Acute Coronary Syndrome (ACS)
Heny Martini, MD, FIHA
Department of Cardiology and Vascular Medicine
Faculty of Medicine, Universitas Brawijaya
Saiful Anwar General Hospital, Malang
73
74. Admission Chest Pain
Persistent
ST-elevation
ST/T -
abnormalities
ECG
Normal or
undetermined
ECG
Working
diagnosis
ACS / Acute Coronary Syndrome
STEMI
Diagnosis NSTEMI/ UAP
Troponin
Rise/fall
Troponin
normal
Bio-chemistry
NSTEMI UAP
Diagnosis STEMI 74
75. STEMI
1. Revascularization
2. Anti - Thrombotic
3. Anti - Ischemia
NSTEACS
1. Anti - Ischemia
2. Anti - Thrombotic
3. Revascularization
Choice of Therapy
75
76. Haemostasis and Coagulation:
Sites of Antithrombotic Drug
Action
Fibrinolytics
Tissue factor
Plasma clotting
cascade
Prothrombin
Thrombin
Fibrinogen Fibrin
Thrombus
Platelet aggregation
Platelet activation
Collagen
Thromboxane A2
ADP
Factor
Xa
Aspirin
Clopidogrel
Prasugrel
Cangrelor
Eptifibatide
Abciximab
Tirofiban
(GPI)
76
80. Acute Coronary Syndrome:
A Major Cause of Mortality and Morbidity
UA/NSTEMI
ā¢ In-hospital death and re-infarction: 5-10%1
ā¢ Six-month mortality in the GRACE registry2 (from admission to 6
months):
- NSTEMI: 13%
- UA: 8%
STEMI
ā¢ 1/3 of STEMI patients will die within 24 h of the onset of ischemia1
ā¢ In-hospital death and reinfarction: 8-10%3
ā¢ One-month mortality: 6-7%4
1 .Grech & Ramsdale. Acute coronary syndrome : unstable angina and non-ST segment elevation myocardial infarction. BMJ 2003;326:1259-61;
2. Fox. et al. An international on acute coronary syndrome care: Insight from the global registry of acute coronary event Am Heart. Et al J 2004:148:S40-5;
3. Antman et al. ACC/AHA guideline for the management of patiets with ST-Elevation Myocardial infarction. Circulation 2004;110:e82-292;
4. Van de Werf et al. Management of acute myocardial infarction in patients presenting with ST-segment Elevation. Eur Heart J 2003;24:28-66
80
81. Moscucci et al. Predictor of majaor bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE) Eur
Heart J 2003;24:1815-23
GRACE Registry in 24,045 ACS patients
*After adjustment for comorbidities, clinical presentation, and hospital therapies.
**p<0.001 for differences in unadjusted death rates
OR (95% CI)
1.64 (1.18 to 2.28)*
0
Overall ACS UA NSTEMI STEMI
10
20
30
40
**
**
**
**
5.1
18.6
3.0
16.1
5.3
15.3
7.0
22.8
Inhospital
death
(%)
Inhospital major bleeding Yes
No
Major Bleeding is Associated with an Increased
Risk of Hospital Death in ACS Patients
81
82. Inhibition of platelet aggregation
High risk of
ischemic events
High risk of
bleeding events
āSweet spotā
Ischemic risk Bleeding risk
Ferreiro & Angiolillo. Thromb Haemost 2010 (in press)
Balancing Safety and Efficacy
82
83. Ischemic
Complications
Hemorrhage
HIT
āŗ Major Bleeding
āŗ Minor Bleeding
āŗ Thrombocytopenia
Evolving Paradigm for Evaluating
ACS Management Strategies
āŗ Death
āŗ MI
āŗ Urgent Target Vessel
Revascularization
Composite Adverse Event Endpoints
83
84. Periprocedural
Complications
Clinical
Benefit
āŗ Death
āŗ Major Disability
āŗ Cost
āŗ Ease of Use
āŗ Duration of Therapy
āŗ Accounting for
Bleeding and
Ischemic Endpoints
Evolving Paradigm for Evaluating
ACS Management Strategies
Composite Adverse Event Endpoints
84
85. Selection of Therapy in the Emergency
Room Must Include Consideration of
Bleeding Risk
āŗAge
āŗGender
āŗRenal insufficiency
āŗBaseline anemia
āŗExpectation of prolonged medical therapy
85
86. Evolution of ACS Therapies
Adapted from White HD et al. Lancet 2008; 372: 570ā84
Aspirin
Heparin
1990 1996 1997 2000 2001 2005 2007 2008
Year
Low molecular
weight heparin
IIb/IIIa receptor
antagonist
Early invasive management
CLOPIDOGREL
Atorvastatin
Fondaparinux
Bivalirudin
Integrated
strategy
PRASUGREL
86
88. Mechanism of Action
ā¢ GpIIb/IIIa blockers inhibit platelet integrin
adhesion receptors (Ī±IIbĪ²3 receptor)
ā¢ Block final platelet activation and cross-
linking by fibrinogen and von Willebrand
factor
ā¢ No further platelet shape change
Opie LH, Gersh BJ. Drugs for the heart. 8th ed. 2013.
88
89. Pharmacological Profile GpIIb/IIIa
Blockers
Compound and
Indications
Supporting
Trials
Pharmacokinetics Doses
Abciximab
1. PCI
2. Unstable
angina
requiring PCI
within 24 h
CAPTURE,
EPIC, EPILOG,
EPISTENT,
TARGET
Monoclonal antibody
High affinity to platelet
receptor; 67% bound to
receptor; plasma t1/2 10-30
min; remains platelet-bound
in circulation up to 15 days
with some residual activity
0.25 mg/kg bolus 10-60 min before
PCI, then 0.125 mcg/kg/min up to
max of 10 mcg over 12 h, up to 24 h
if ACS with planned PCI
Eptifibatide
1. PCI
2. NSTEACS
IMPACT-II,
PURSUIT,
ESPRIT
Cyclic heptapeptide
Lower receptor affinity than
others; plasma t1/2 2-3 h; renal
clearance 50%
180 mcg/kg bolus, then 2
mcg/kg/min up to 72 h
Reduce dose to 0.5 mcg/kg/min at
time of PCI, then for 20-24 h post-
PCI. If no prior ACS but PCI, 135
mcg/kg bolus then 0.5 mcg/kg/min
Tirofiban
1. NSTEACS
2. STEMI
PRISM, PRISM-
Plus RESTORE
On TIME 2
Peptidomimetic nonpeptide
Intermediate affinity for
receptor, closer to abciximab;
hence 35% unbound in
circulation, renal (65%) and
fecal (25%) clearance
1. NSTEMI, two stage infusion: 0.4
mcg/kg/min for 30 min, then 0.1
mcg/kg/min up to 48 h
2. STEMI, 25 mcg/kg bolus over 3
min and 0.15 mcg/kg/min
maintenance infusion for up to
18 hours
89
93. 1. PURSUIT Study: Multicentre study,
Double-Blind, Randomized
10,948 patients with UA/NSTEMI undergoing PCI
Eptifibatide
A bolus dose of 180 Ī¼g per kilogram of body
weight, followed by an infusion of 1.3 Ī¼g per
kilogram per minute, or a bolus dose of 180 Ī¼g
per kilo- gram followed by an infusion of 2.0 Ī¼g
per kilogram per minute
Aspirin, Clopidogrel/Ticlopidine,
Heparine iv/sc, PCI
Randomization
Placebo
Bolus and infusion of placebo
Death or myocardial infarction within 30 days 93
94. Primary End Point: Death/MI in 30 days
Zeymer
ed end point of death and myocardial infarction at different time points in the PURSIUT-study. B. Death
7.6
9.1
11.6
15.7
5.9
7.6
10.1
14.2
0
2
4
6
8
10
12
14
16
18
Placebo
(n = 4739)
INTEGRILINĀ®
(n = 4722)
72 h
1.7%
(p = 0.001)
96 h
1.5%
(p = 0.01)
7 days
1.5%
(p = 0.016)
30 days
1.5%
(p = 0.042)
15.6
16.7
14.5
11.6
-1
4
9
14
19
24
Conservative PCI < 72 h
Placebo Eptifibatide
Death/MI
until
day
30
(%)
Death/MI
until
day
30
(%)
ā¢ In the patients who
underwent PCI during the
first 72 h of the trial, the
composite end point was
significantly lower in the
eptifibatide group
compared with placebo
(11.6 versus 16.7%; p =
0.01), but it was not
significantly different in
patients who were not
receiving PCI
THE PURSUIT INVESTIGATORS: Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary
syndromes. N. Engl. J. Med. (1998) 339(7):436-443.
94
95. Incidence of Death or Nonfatal MI at 30
days
998)
1.5
%
THE PURSUIT INVESTIGATORS: Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary
syndromes. N. Engl. J. Med. (1998) 339(7):436-443.
95
96. 2. EARLY-ACS Study: International, Multicenter, Double-
Blind, Randomized, Placebo-Controlled Trial
+ delayed
eptifibatide
for 18-24 h
after PCI
GIUGLIANO RP, NEWBY LK, HARRINGTON RA et al.: The early glycoprotein IIb/IIIa inhibition in non-ST-segment elevation acute
coronary syndrome (EARLY ACS) trial: a randomized placebo-controlled trial evaluating the clinical benefits of early front-loaded
eptifibatide in the treatment of patients with non-ST-segment elevation acute coronary syndrome ā study design and rationale.
Am. Heart J. (2005) 149(6):994-1002.
96
97. 3. Early vs Delayed, Provisional Eptifibatide
in Acute Coronary Syndrome
Giugliano, R. P., White, J. A., Bode, C., Armstrong, P. W., Montalescot, G., Lewis, B. S., van 't Hof, A., Berdan, L. G., Lee, K. L., Strony, J. T.,
Hildemann, S., Veltri, E., Van de Werf, F., Braunwald, E., Harrington, R. A., Califf, R. M., Newby, L. K. Early versus delayed, provisional
eptifibatide in acute coronary syndromes N Engl J Med. 2009;360(21):2176-90
97
98. 4. ESPRIT Study : Multicenter, Randomised, Double-Blind,
Placebo-Controlled Trial
2,064 patients undergoing
elective native coronary PCI
98
OāSHEA JC, BULLER CE, CANTOR WJ et al.: Long-term
efficacy of pletelet glycoprotein IIb/IIIa integrin
blockade with eptifibatide in coronary stent
intervention. JAMA (2002) 287:618-621.
99. Primary End Point: Death/MI/Urgent Target Vessel
Revascularization and Thrombotic Bail-Out 48 h
Novel dosing regimen of eptifibatide in planned coronary
(ESPRIT): a randomised, placebo-controlled trial
It was significantly reduced with
eptifibatide versus placebo (6.6
versus 10.5%; p = 0.0015)
OāSHEA JC, BULLER CE, CANTOR WJ et al.: Long-term efficacy of pletelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in
coronary stent intervention. JAMA (2002) 287:618-621. 99
100. Probability of Composite Endpoint of
Death and MI
Cumulative
event
rate
(%)
Days of randomisation
100
OāSHEA JC, BULLER CE, CANTOR WJ et al.: Long-term efficacy of pletelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in
coronary stent intervention. JAMA (2002) 287:618-621.
101. Probability of Composite Endpoint of
Urgent Target Vessel Revascularization
Cumulative
event
rate
(%)
Days of randomisation
101
OāSHEA JC, BULLER CE, CANTOR WJ et al.: Long-term efficacy of pletelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in
coronary stent intervention. JAMA (2002) 287:618-621.
102. Stroke and Bleeding Complications
Major bleeding was infrequent, but arose
more often with eptifibatide than with
placebo (1.3 versus 0.4%; p = 0.027)
OāSHEA JC, BULLER CE, CANTOR WJ et al.: Long-term efficacy of pletelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in
coronary stent intervention. JAMA (2002) 287:618-621. 102
103. 5. TITAN-TIMI 34 Study
To answer the following question:
Among patients intended to undergo primary
PCI, does a strategy of early initiation of
eptifibatide in the ER prior to primary PCI yield
superior pre-PCI angiographic outcomes
compared to a strategy of initiating eptifibatide
in the cardiac catheterization laboratory after
diagnostic angiography?
103
GIBSON CM, KIRTANE AJ, MURPHY SA et al.: Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for
ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34trial. Am. Heart J. (2006)
152:668-675.
104. Primary PCI
STEMI < 6 HRS Undergoing Primary PCI (n=343)
TITAN TIMI 34: Study Design
RANDOMIZE
Open Label
ASA 160-325 mg po
HEPARIN 60 U/kg bolus (Max 4000U) and 7U/kg
infusion (Max 800 U/hr)
āEARLY ER EPTIFIBATIDEā āCATH LAB EPTIFIBATIDEā
EPTIFIBATIDE 180/2.0/180
TRANSFER TO CATH LAB
DIAGNOSTIC ANGIO
PRIMARY ENDPOINT: Pre PCI TIMI Frame Count
EPTIFIBATIDE 180/2.0/180
TRANSFER TO CATH LAB
DIAGNOSTIC ANGIO
GIBSON CM, KIRTANE AJ, MURPHY SA et al.: Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-
segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34trial. Am. Heart J. (2006) 152:668-675.
104
105. TITAN-TIMI 34: Enrollment
Criteria
Inclusion Criteria:
ā¢ > 18 years of age
ā¢ Clinical diagnosis of AMI ( ischemic pain > 20 min. )
ā¢ Onset of symptoms < 6 hours
ā¢ ST elevation > 1 mm in 2 contiguous limb leads or >2 mm in 2
contiguous precordial leads
Major Exclusion Criteria:
ā¢ Hemorrhagic risk factors
ā¢ Current episode previously treated by fibrinolytics
ā¢ Cardiogenic shock or hemodynamically significant
arrhythmias
105
106. TITAN-TIMI 34: Pre-PCI TIMI Grade 2 or 3 Flow
and Full Perfusion
0%
10%
20%
30%
40%
50%
Pre
-
PCI
TIMI
2
or
3
Flow
(%)
ER
Eptifibatide
Cath Lab
Eptifibatide
46.8%
34.2%
(59/126) (39/114)
p = 0.047
Secondary Analysis: Treated per Protocol
0%
10%
20%
30%
Full
Angiographic
Perfusion
(%)
ER
Eptifibatide
Cath Lab
Eptifibatide
23.9%
13.2%
p = 0.041
Full Angiographic Perfusion previously defined in Gibson CM. Am Heart J. 2004 Aug;148(2):336-40.
(28/117) (14/106)
106
107. 0
5
10
15
20
25
Post
-
PCI
CTFC
ER
Eptifibatide
Cath Lab
Eptifibatide
20
22
p = 0.14
0
20
40
60
80
100
Post
-
PCI
TIMI
3
Flow
(%)
ER
Eptifibatide
Cath Lab
Eptifibatide
86.7% 89.1%
p = NS
0
5
10
15
20
25
30
35
40
Post
-
PCI
TMPG
3
(%) ER
Eptifibatide
Cath Lab
Eptifibatide
37.0% 36.7%
p = NS
(47/128)
(57/154)
(n=138) (n=116) (137/158) (122/137)
Primary Analysis: Modified Intent-to-Treat
TITAN-TIMI 34 Post-PCI Flow
107
GIBSON CM, KIRTANE AJ, MURPHY SA et al.: Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for
ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34trial. Am. Heart J. (2006)
152:668-675.
108. 2,3
2,1
0
1
2
3
Death
(%)
ER
Eptifibatide
Cath Lab
Eptifibatide
Death
p = NS
2,9
7,1
0
2
4
6
8
CHF
(%)
ER
Eptifibatide
Cath Lab
Eptifibatide
n=173 n=142
Primary Analysis: Modified Intent-to-Treat
TITAN-TIMI 34 Clinical Endpoints at
Discharge/Day 5
CHF
p = 0.082
n=173 n=142
108
GIBSON CM, KIRTANE AJ, MURPHY SA et al.: Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-
segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34trial. Am. Heart J. (2006) 152:668-675.
109. Outcome
ER
Eptifibatide
(n=174)
Cath Lab
Eptifibatide
(n=142)
P-value
TIMI Major (Hgb ļÆ >5 g/dL or
ICH)
1.7% 3.5% NS
TIMI Minor (Hgb ļÆ 3-5 g/dL) 5.2% 4.2% NS
TIMI Major or Minor 6.9% 7.8% NS
Transfusion PRBC 9.8% 7.0% NS
Stroke or ICH 0.0% 0.0% NS
Thrombocytopenia (Plt. <
100K) 2.3% 1.4% NS
TITAN-TIMI 34: Bleeding Events
Non CABG Through Discharge; Site Assessment
Primary Analysis: Modified Intent-to-Treat
109
NS: non significant
110. Epicardial flow associated with early
versus delayed Gp IIb/IIIa inhibitors
The improvements in epicardial flow associated
with early eptifibatide administration in the
present study are also consistent with the
epicardial flow data that have been reported
previously for both abciximab and tirofiban
Gibson CM, de Lemos JA, Murphy SA, et al. Combination therapy with abciximab reduces angiographically evident
thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation 2001;103:2550 - 4. 110
111. 6. Efficacy and safety of eptifibatide vs
tirofiban : A systematic review and
meta-analysis
Zhou X, Wu X, Sun H, Li J. Efficacy and safety of eptifibatide versus tirofiban in acute coronary syndrome
patients: a systematic review and meta-analysis. J Evid Based Med. 2017;10:136ā144.
111
112. Efficacy and Safety Endpoints in ACS:
Eptifibatide vs Tirofiban
When compared with tirofiban, eptifibatide was associated with an
absolute risk reduction of 5.3% (7.71% vs 13.0%) and there was a
significant difference between the two treatment groups for TIMI
minor bleeding (RR 0.61, 95% CI 0.38 to 0.98, P = 0.04)
Zhou X, Wu X, Sun H, Li J. Efficacy and safety of eptifibatide versus tirofiban in acute coronary syndrome patients: a systematic
review and meta-analysis. J Evid Based Med. 2017;10:136ā144.
112
113. TIMI Flow Grade 3 in Patients with
ACS: Eptifibatide vs Tirofiban
The risk of TIMI flow grade 3 was slightly lower in eptifibatide group
(83.62% vs 84.34%). However, the difference was not significant between
the two treatment groups (RR 1.04, 95% CI 0.82 to 1.31, P = 0.75)
Zhou X, Wu X, Sun H, Li J. Efficacy and safety of eptifibatide versus tirofiban in acute coronary syndrome patients: a systematic
review and meta-analysis. J Evid Based Med. 2017;10:136ā144.
113
114. Local Intracoronary Eptifibatide vs Mechanical
Aspiration
in Patients with STEMI
ā¢ In the infusion catheter
group 68% of patients
had MBG 3 compared to
36% of patients in
thrombus aspiration
group and 20% of
patients in the control
group (p value = 0.002)
ā¢ The infusion had cTFC
shorter than the
aspiration and control
group (20.76 Ā± 4.44
versus 26.68 Ā± 8.40 and
28.16 Ā± 5.96),
respectively (š value =
0.001)
cTFC: corrected TIMI frame count
Hamza MA, Galal A, Suweilam S, Ismail M. Local intracoronary eptifibatide versus mechanical aspiration in patients with acute ST-elevation myocardial infarction.
International Journal of Vascular Medicine. 2014;1:1-5.
119. Dosing of Gp IIb/IIIa inhibitors in
patients with normal and impaired
renal function
119
120. The Role of Gp IIb/IIIa inhibitors
in Management of Acute
Coronary Syndrome (ACS) for
STEMI
120
121. STEMI Guideline
Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, dkk. 2017 ESC Guideline for the management of acute
myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J;00:1-66.
121
122. Recommendations for Gp IIb/IIIa
inhibitors
ā¢ Using GP IIb/IIIa inhibitors as
bailout therapy in the event of
angiographic evidence of a large
thrombus, slow- or no-reflow, and
other thrombotic complications is
reasonable, although this strategy
has not been tested in a
randomized trial
ā¢ Overall, there is no evidence to
recommend the routine use of Gp
IIb/IIIa inhibitors for primary PCI
122
123. Doses of Gp IIb/IIIa inhibitors in primary
PCI
Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, dkk. 2017 ESC Guideline for the management of acute
myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J;00:1-66.
123
124. Doses adjustment of Gp IIb/IIIa inhibitors
in renal dysfunction
Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, dkk. 2017 ESC Guideline for the management of acute myocardial
infarction in patients presenting with ST-segment elevation. Eur Heart J;00:1-66.
124
129. Take Home Message
ļ¼ The binding of ligand and other adhesive proteins to platelets by means of the
Glycoprotein (GP) IIb/IIIa receptor serves as āthe final common pathwayā of
platelet-thrombus formation. GPIIb/IIIa receptor antagonists inhibit the binding
fibrinogen to activated platelet GPIIb/IIIa receptors and, therefore, prevent the
formation of platelet thrombi. Additional antithrombin therapy should be given
in connection with GPIIb/IIIa administration.
ļ¼ In management of ACS, we need to consider the efficacy versus safety of
antithrombotic that we use, including GP IIb/IIIa inhibitors
ļ¼ Based on several studies and gidlines, eptifibatide is recommended as bailout
therapy in the event of angiographic evidence of a large thrombus, slow- or no-
reflow, and other thrombotic complications
129
131. Take Home Message
ļ¼In management of ACS, we need to consider the efficacy versus safety of
antithrombotic that we use, including GP IIb/IIIa inhibitors
ļ¼Based on several studies in patients with NSTEMI, eptifibatide is
recommended as upstream therapy and during PCI in ACS patients with
NSTEMI
ļ¼Eptifibatide is effective in reducing ischemic complications of patients
undergoing elective PCI
ļ¼Eptifibatide given early, before planned primary PCI, is associated with
pre-PCI patency rates of the infarct-related artery, comparable to those
observed with abciximab and tirofiban
ļ¼Evidence to date demonstrates that the safety of eptifibatide is slightly
superior to tirofiban in patients with ACS. However, there were similar
results on efficacy
131
