Visual Exploration of Clinical and Genomic Data for Patient Stratification
acs risk stratification and clinical management
description
Transcript of acs risk stratification and clinical management
-
CURRICULUM VITAEName Dr. Anwar Santoso, PhD, FIHA, FAsCC, FICA, FACCPlace & Date of
birth
Surabaya, 20 July
Official
designation
Lecturer in Dept. of Cardiology Faculty of Medicine ~ University of Indonesia,
Jakarta - Indonesia
Clinical Researcher in Division of Cardiovascular Research of National
Cardiovascular Centre Harapan Kita Hospital, Jakarta - Indonesia
Consultant Cardiologist in Harapan Kita Hospital, Jakarta - Indonesia
Academic rank Lektor Kepala (gol IV-D) Associate Professor
Office Address Jl. Letjen S Parman kav 87, Jakarta Barat 11420, Indonesia,
Phone: +62 21 568 1149; Fax: +62 21 568 4220
Educational
background
1. Medical Doctor, Airlangga University, School of Medicine, Indonesia.
2. Cardiologist, Airlangga University, School of Medicine, Indonesia, 1992
3. PhD, Udayana University, Post Graduate Program, Bali - Indonesia, 2005
4. Cardiology Consultant, Indonesian Heart Association, 2004
5. Advanced Cardiology Training Epworth Hospital & Victoria Heart Centre in
Melbourne, 1996
Professional
Society
Memberships
1. The Indonesian Medical Association, member, 1993 - now
2. Indonesian Heart Association, member, 1993 now
3. President of Indonesian Heart Association, 2014 2016
4. Indonesian Internal Medicine Society, member, 1993 - now
5. Indonesian Atherosclerosis and Vascular Disease Association, member, 1996 - now
6. Asean College of Cardiology, fellow, 2009 now
7. International College of Angiology, fellow, 2012 now
8. American College of Cardiology, fellow, 2014 - now
-
Anwar SantosoDept. of Cardiology Faculty of Medicine; University of Indonesia
National Cardiovascular Centre Harapan Kita HospitalPresident of Indonesian Heart Association
Jakarta - Indonesia
Acute Coronary Syndromes:
Risk stratification and how to deal with?
-
Disclosure
Speaker has received honorarium from the following industry as an independent advisory board
Astra Zeneca
Merck Sharpe & Dome
Pfizer
Takeda
-
Outlines
Challenges of ACS management in Asia Pacific
Risk stratifications and the issues in ACS
What the recent guidelines teach us?
Summary
4
-
AsPac ACS Medical Management Working Group, Int J Cardiol 2015; (183): 63 - 75
-
AsPac ACS Medical Management Working Group, Int J Cardiol 2015; (183): 63 - 75
Overview of main international and AsPac ACS Guidelines
-
Accessibility/systems of care
Recommendations
Shorten the delay between patient first experiencing symptoms and FMC
Encourage regional co-ordination of ambulance services
Encourage ambulance services to liaise with hospitals and perform pre-hospital triage and pre-hospital fibrinolysis where appropriate
Establish rapid assessment protocols in the ER
Utilize existing infrastructure more efficiently through cardiac networks
Barriers Unmet needs
Geographical barriers Significant delays between symptom
onset and FMC
Limited ambulance services, equipment
and staff
Low rates of pre-hospital triage and
fibrinolysis
Limited PCI-capable facilities and
manpower and lack of access to
guideline-approved drugs
Disparity in quality of care
AsPac ACS Medical Management Working Group, Int J Cardiol 2015; (183): 63 - 75
-
Risk stratification
Recommendations
Recommend risk assessment at first medical contact
Identify high-risk groups (ethnicity, obesity, diabetes, renal dysfunction)
Recommend use of formal risk scores (primarily GRACE)
Validate TIMI and GRACE risk scores using Asia-Pacific registry data
Develop decision support tools to complement risk tools
Consider bleeding risk
Barriers Unmet needs
Risk factors and ethnic profiles vary
within the Asia-Pacific region
Subjective estimation of patient
risk and under-estimation of
treatment benefit
Variability in use of structured models for
risk stratification
Disparity in formal risk assessment
AsPac ACS Medical Management Working Group, Int J Cardiol 2015; (183): 63 - 75
-
Education
Recommendations
Improve public awareness and plan of action to avoid late presentation
Enlist cardiac society/industry support to disseminate guidelines and educate patients
Promote national and individual smoking cessation initiatives
Educate non-cardiac physicians
Barriers Unmet needs
Low public awareness of ACS signs and
symptoms and risk factors
Significant delays between symptom
onset and FMC
Poor patient compliance with lifestyle
modification and pharmacotherapy
Sub-optimal long-term
secondary prevention
Low rates of guideline adherence DAPT use varies greatly between Asia-
Pacific countries
Lack of familiarity with new drugs
amongst non-cardiac physicians
Adoption of newer, more potent P2Y12receptor antagonists is slow
AsPac ACS Medical Management Working Group, Int J Cardiol 2015; (183): 63 - 75
-
Cost/affordability
Recommendations
Prioritize treatment to achieve the greatest benefit with available funding:
Aspirin immediately and continued indefinitely
Statin therapy in hospital, continued indefinitely irrespective of LDL-C
DAPT for 12 months with a newer potent antiplatelet if feasible
Oral BBs in the medium term
Long-term ACEi/ARBs in presence of LV dysfunction
Aldosterone antagonists in presence of LV dysfunction
Barriers Unmet needs
User-funded healthcare systems in some
countries
Inequity in standards of care
Reimbursement systems Limited real-world access to optimal pharmacotherapy
AsPac ACS Medical Management Working Group, Int J Cardiol 2015; (183): 63 - 75
-
Risk Stratification is important in NSTE-ACS
Management
TIMI SCORE GRACE SCORE
recommended as the preferred
classification to apply on admission and at
discharge in daily clinical routine practice
Less accurate in predicting events but its
simplicity makes it useful and widely
accepted
Hamm W et al. European Heart Journal 2007; 28:15981660; Hamm CW et al. Eur Heart J 2011;32:2999 3054
CLINICAL CONDITION1
2 3
-
PRIMARY
Relevant rise or fall in troponin Dynamic ST- or T-wave changes
(symptomatic or silent)
SECONDARY
Diabetes mellitus Renal insufficiency
(eGFR
-
TIMI SCORE
Age 65 years or older?
At least 3 risk factors for CAD?
Prior coronary stenosis of 50% or more?
ST-segment deviation on ECG 0.5mm?
Use of aspirin in prior 7 days
At least 2 anginal events in prior 24 hours?
Elevated serum cardiac markers?
Risk
Score
TIMI risk score for developing at least
1 component of the primary end point
through 14 days after randomization.1
0-1 4.7%
2 8.3%
3 13.2%
4 19.9%
5 26.2%
6- 7 40.9%
Hamm W et al. European Heart Journal 2007;28:15981660
-
GRACE SCORE
Predictor Score
Age, years
< 40 0
40 - 49 18
50 - 59 36
60 - 69 55
70 - 79 73
80 91
Predictor Score
Heart Rate , beats/min
< 70 0
70-89 7
90-109 13
110 - 149 23
150 - 199 36
> 200 46
Predictor Score
Systolic Blood Pressure (mmHg)
< 80 63
80 99 58
100 - 119 47
120 - 139 37
140 - 159 26
160 - 199 11
> 200 0
Predictor Score
Creatinine (mol/L)
0 - 34 2
35 70 5
71 105 8
106 140 11
141 176 14
177 353 23
354 31
Predictor Score
Killip class
I 0
II 21
III 43
IV 64
Predictor Score
Cardiac
arrest at
admission
43
Elevated
cardiac
markers
15
ST Segment
deviation
30
Khalill R et al. Exp Clin Cardiol.2009; 14(2): e25 e30
Risk category
(tertile)
GRACE
Risk Score
In-hospital
death
(%)
Low 108 < 1
Intermediate 109 - 140 1-3
High > 140 > 3
-
Das Sein und Das Sollen
-
Predictive value of the HFA/CSANZ, TIMI and GRACE risk
score for major adverse cardiac events within 30 days
Cullen L, et. al. Heart, Lung and Circulation 2013: 22: 844 - 51
-
Accuracy of GRACE in predicting MACE
in 3 ethnics in Singapore
Chan MY, et. al. Am Heart J 2011: 0: 1 - 9
GRACE risk score is underpredicted in Asian ACS management should be more agressive
-
Cath lab or later ?
Benefit of early intervention in high risk patients
Primary endpoint : death, myocardial infarction, or stroke.
Mehta, SR et al. N Engl J Med 2009;360:2165-75.
-
Evidence-based medication in ACS in China and India
Bi Y, et. al. Am Heart J 2009: 157: 509 516. e1 Xavier D, et. al. The Lancet 2008: 371: 1435 - 42
-
Use of evidence based-treatment in low-, moderate- and
high-risk ACS in Korea and Singapore
Chan MY, et. al. Am Heart J 2011: 0: 1 - 9Lee JH, et. al. Am Heart J 2010: 159: 1012 - 19
-
Proportions and reasons for non-adherence in
Chinese ACS patients
Bi Y, et. al. Am Heart J 2009: 157: 509 516. e1
-
Das Sein und Das Sollen
-
Timing of angiography for NSTE-ACS
Refractory angina Severe heart Failure Life-threatening ventricular
arrhythmias, or Hemodynamic
instabilityAt least one < 2 hour
Urgent coronary angiography
Relevant rise or fall in troponin Dynamic ST- or T-wave changes
(symptomatic or silent)
Grace risk score > 140
none
none
Diabetes mellitus Renal insufficiency (eGFR
-
Initial Treatment
Hamm CW et al. Eur Heart J 2011;32:2999 3054
Initial Therapeutic Measures Checklist of treatments when an ACS
diagnosis appears likely
-
Oral Antiplatelet Plays Important Role in ACS
1. Bode C and Huber K. European Heart Journal Supplements. 2008: 10 (Supplement A), A13A20
2. Bassand JP et al. European Heart Journal 2007;28:15981660
-
Benefit CV Mortality P2Y12 Inhibitor
5,50 5,10
Plasebo Clopidogrel
CURE1
2,40 2,10
Clopidogrel Prasugrel *
TRITON TIMI 382
5,10
4,00
Clopidogrel Ticagrelor
PLATO3
P = NS
n = 12.562
NNT = 250n = 13.608
NNT = 333
n = 18.624
NNT = 91
1.Yusuf S et al. N Engl J Med 2001;345; 2.Wiviott SD e tal. N Engl J Med 2007;357:2001-15; 3.Wallentin L, et al. N Engl J Med. 2009;361:10451057.* Prasugrel is not yet approved and available in Indonesia
Ra
te o
f C
V d
ea
th (
%)
P = N/A P = 0.001
-
ESC 2012 STEMI guidelines:
periprocedural antiplatelet therapy in PPCI
Recommendations Class Level
ASA oral or iv (if unable to swallow) is recommended I B
An ADP receptor blocker is recommended in addition to ASA.
Options are:I A
Prasugrel* in clopidogrel-nave patients, if no history of prior
stroke/TIA, age
-
ESC/EACTS 2014 Guidelines on
myocardial revascularization1
2
8
1. Kolh P et al. Eur Heart J August 29 2014; DOI:10.1093/eurheart/ehu278 [Epub ahead of print]
2. Bellemain-Appaix A et al. JAMA 2012;308:25072516
3. Zeymer U et al. Clin Res Cardiol 2012;101:305312
4. Koul S et al. Eur Heart J 2011;32:29892997
5. Dorler J et al. Eur Heart J 2011;32:29542961
Recommendation in STEMI Class Level Evidence
A P2Y12 inhibitor is recommended in
addition to ASA and maintained over 12
months unless there are
contraindications such as excessive
bleeding
I A/B
PLATO
TRITON
CURRENT-OASIS 7
It is recommended to give P2Y12inhibitors at the time of first medical
contact
I B 2,3,4,5
-
2014 AHA/ACC NSTEACS Guidelines
Recommendations Dosing and
special consideration
Class / Level
P2Y12 inhibitors
Clopidogrel loading dose followed by daily
maintenance dose in patients unable to take aspirin
75 mg
P2Y12 inhibitor, in addition to aspirin, for up to 12
months for patients treated initial with either an early
invasive or initial ischemia-guided therapy :
a. Clopidogrel 300 mg or 600 mg loading
dose, then 75 mg/d
b. Ticagrelor* 180 mg loading dose, then 90
mg BID
P2Y12 inhibitor therapy (clopidogrel, prasugrel, or
ticagrelor) continued for at least 12 months in post-
PCI patients treated with coronary stents
N/A
Ticagrelor in preferable to clopidogrel for patients
treated with an early invasive or ischemia-guided
therapy
N/A
IB
IB
IB
IIaB
*The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily
Amsterdam EA et al. J Am Coll Cardiol Sept 23, 2014 Epub ahead of print. DOI:10.1016/j.jack.2014.09.017
-
Short-term (< 6 months) versus long-term (1 year) DAPT in post stent CAD?
Evolving issues?
How to deal with stable CAD after 1 year?
-
Palmerini T, et al. J Am Coll Cardiol 2015; 65: 1092 102.
-
Palmerini T, et al. J Am Coll Cardiol 2015; 65: 1092 102.
Dual anti-platelet therapy duration after DES
-
Palmerini T, et al. J Am Coll Cardiol 2015; 65: 1092 102.
Patient subgroups and DAPT duration
-
PEGASUS-TIMI 54
A randomised, double-blind, placebo-controlled,
parallel-group, multinational trial to assess the prevention
of thrombotic events with ticagrelor compared with placebo
on a background of acetylsalicylic acid therapy in patients
with a history of myocardial infarction
The PEGASUS-TIMI 54 study investigates the efficacy and safety of ticagrelor in
an unlicensed patient population. Therefore this slide deck is restricted solely for
Medical Affairs use in Scientific Exchange activities and is for reactive use only
Please ensure local review prior to external use
-
PEGASUS-TIMI 54: Rationale (1)
Patients who have suffered a MI are at heightened risk of recurrent ischaemic events13
The recent APOLLO-HELICON registry highlighted that 1 in 5 patients who remain event free 1 year post-MI will go on to suffer another MI, a stroke, or die from CV
causes in the subsequent 3 years3
These data suggest that patients with a history of MI may derive particular benefit from intensive secondary prevention strategies
However, the role of P2Y12 receptor antagonists in long-term secondary prevention after MI has not been established
Both US and European ACS practice guidelines currently recommend treatment with a P2Y12 receptor antagonist for up to 1 year after MI
47
CV, cardiovascular; MI, myocardial infarction
1. Bhatt DL et al. JAMA 2010;304:135013572. Fox KA et al. Eur Heart J 2010;31:275527643. Jernberg T et al. Eur Heart J 2015; pii: ehu505 [Epub ahead of print]
4. Amsterdam EA et al. Circulation 2014;130:235423945. Hamm CW et al. Eur Heart J 2011;32:299930546. O'Gara PT et al. Circulation 2013;127:e362425 7. Steg PG et al. Eur Heart J 2012;33:25692619 35
-
PEGASUS-TIMI 54: Rationale (2)
Ticagrelor is a potent, reversibly binding, direct-acting agent P2Y12receptor antagonist that has low inter-individual variability1
Ticagrelor also increases endogenous adenosine levels via inhibition of
the equilibrative nucleoside transporter-12
When added to ASA for up to 1 year after an ACS event, ticagrelor
90 mg bid reduced the rate of major adverse CV events, including CV
death, as compared with clopidogrel 75 mg once daily, with an accrual
of benefit over time3
Building on these observations, the PEGASUS-TIMI 54 trial was
designed to test the hypothesis that long-term therapy with ticagrelor
added to low-dose ASA will reduce the risk of major adverse CV events
in high-risk patients with a history of MI
36
1. Husted S et al. Eur Heart J 2006;27:103810472. Cattaneo M et al. J Am Coll Cardiol 2014;63:250325093. Wallentin L et al. N Engl J Med 2009;361:10451057
-
PEGASUS-TIMI 54: Study Design
Patients aged 50 years with a history of spontaneous MI 13 years prior to enrolment AND at least one additional atherothrombosis risk factor*
(N=21,162)
Ticagrelor 60 mg bid
+ ASA 75150 mg/day
Minimum of 12 months follow up:Every 4 months in Year 1,
then semi-annually
Primary efficacy endpoint: CV death, MI or stroke
Primary safety endpoint: TIMI-defined major bleeding
Placebo
+ ASA 75150 mg/dayTicagrelor 90 mg bid
+ ASA 75150 mg/day
*Age 65 years, diabetes mellitus, second prior MI, multivessel CAD or chronic non-end stage renal disease bid, twice daily; CAD, coronary artery disease; TIMI, Thrombolysis in Myocardial Infarction
Bonaca MP et al. Am Heart J 2014;167:437444Bonaca MP et al. N Engl J Med 2015 [Epub ahead of print] 37
-
PEGASUS-TIMI 54: Primary Endpoint
38
CI, confidence interval; HR, hazard ratio
Bonaca MP et al. N Engl J Med 2015 [Epub ahead of print]
No. at risk
Placebo
90 mg bid
60 mg bid
7067
7050
7045
6979
6973
6969
6892
6899
6905
6823
6827
6842
6761
6769
6784
6681
6719
6733
6508
6550
6557
6236
6272
6270
5876
5921
5904
5157
5243
5222
4343
4401
4424
3360
3368
3392
2028
2038
2055
Eve
nt
rate
(%
)
Months from randomisation
Ticagrelor 60 mg vs placebo
HR 0.84 (95% CI 0.740.95) P=0.004
Ticagrelor 90 mg vs placebo
HR 0.85 (95% CI 0.750.96) P=0.008
9.04% Placebo
7.85% 90 mg bid
7.77% 60 mg bid
Placebo
Ticagrelor 90 mg bid
Ticagrelor 60 mg bid
0 3 6 9 12 15 18 21 24 27 30 33 36
0
1
2
3
4
5
6
7
8
9
10
-
PEGASUS-TIMI 54: Efficacy Endpoints
*Indicates nominal P value; P
-
-50
-40
-30
-20
-10
0
10
20
30
40
50
PEGASUS-TIMI 54: Estimates of First Efficacy
and Bleeding Events Prevented and Caused
Rates are annualised from 3-year Kaplan-Meier event rates in the intention-to-treat population
Bonaca MP et al. N Engl J Med 2015, Supplementary Appendix [Epub ahead of print]
Ticagrelor 90 mg bid
Ticagrelor 60 mg bid
CV death, MI or stroke
TIMI major bleeding
Nu
mb
er
of e
ve
nts
pe
r 1
0,0
00
pa
tie
nts
initia
ted
on
tre
atm
ent fo
r 1
ye
ar
-40-42
41
31
40
-
Summary
Each Asia-Pacific country faces a unique set of barriers that prevent optimal translation of evidence-based guideline recommendations into practice
Establishing cardiac networks and local/individual hospital models/clinical pathways will be central to optimization of ACS medical management in the Asia-Pacific region
Validation study of ACS risk assessment should be encouraged onto our own population
Reperfusion and DAPT are standard treatment in ACS management
Long-term DAPT strategy is promising strategy to reduce late restenosis in stable CAD, with concerning to bleeding risk