Copyright © 2008 National University Health System Is Platelet Reactivity Testing in Acute Coronary Syndromes Really Relevant?. Chan, MBBS, MHS, MRCP, FACC National University Heart Cen
Trang 1Copyright © 2008 National University Health System
Is Platelet Reactivity Testing in Acute
Coronary Syndromes Really Relevant?
Mark Y Chan, MBBS, MHS, MRCP, FACC National University Heart Centre, Singapore
Yong Loo-Lin School of Medicine Singapore
Trang 2I have the following potential conflicts of
interest to report:
Research contracts – Roche
Diagnostics, Eli Lilly
Consulting –Eli Lilly, Bayer
Healthcare, Astra-Zeneca
Trang 3Copyright © 2008 National University Health System
VerifyNow ®
• Least
operator-dependent
Trang 5Conventional Arm :Prasugrel 5 mg
Group 1
No monitoring
Monitoring Arm :Prasugrel 5 mg
1 st assessment : Verifynow P2Y12: 2 weeks ± 2 d
Group 2
ANTARCTIC design
ANTARCTIC a study by the ACTION Group
PRU≥208
Prasugrel 10 mg/day Prasugrel 5 mg Clopidogrel 75 mg/day
Primary end point (net clinical benefit) over 12 months:: Bleeding type 2,3,5 of the BARC
definition andMACE (CV death, MI, urgent revascularisation, stent thrombosis, stroke)
PRU ≤85
2 nd assessment and adjustment:
Verifynow P2Y12: 2 weeks ± 2 d
85<PRU<208
Trang 6Primary Endpoint
ANTARCTIC a study by the ACTION Group
CV death, MI, stroke, stent thrombosis, urgent
revascularization or
BARC 2, 3 or 5
Trang 7Copyright © 2008 National University Health System
Ischemic Endpoint
CV death, MI, stroke, stent
thrombosis, urgent revascularization BARC 2,3,5
Bleeding Endpoint
ANTARCTIC a study by the ACTION Group
Trang 8Multiplate®
Whole blood Impedance Aggregometry
Trang 9Copyright © 2008 National University Health System
High On-Treatment Platelet Reactivity to Adenosine Diphosphate
Predicts Ischemic Events
Bonello et al., J Am Coll Cardiol 2010 Sep 14;56(12):919-33
Studies are summarized that link high platelet reactivity (“clopidogrel resistance”) to ischemic events (e.g stent thrombosis)
Best predictivity was found for the Multiplate® analyzer (ADPtest) The consensus cut-off for ADPtest on the Multiplate® analyzer is defined as an aggregation
> 46 U (468 AU*min)
Odds ratio (OR) of 12.0 for Multiplate® vs OR of 1.2 – 5.8 in other methods (odds ratio = how much higher is the risk for the patient to suffer an ischaemic event if
having a “clopidogrel resistance”)
Trang 10Copyright © 2008 National University Health System
SMART-ACS
Dual Platelet Reactivity in Acute Coronary Syndrome
Leonardo P de Carvalho 1,2 , MD, PhD; Alan Fong 3 , MBBS; Richard Troughton 4 , MD, PhD, Bryan P., Yan 5 , MBBS; Chee-Tang Chin 6 , MBBS, Sock-Cheng, Poh 1 , Melissa Mejin 3 , Nancy Kwan 5 , Chi-Hang, Lee 1, 7 , MBBS; Adrian F Low 1, 7 , MBBS; Huay-Cheem, Tan 1, 7 , MBBS, MHS; Siew-Pang, Chan 1, 7 ,
Christopher Frampton 4 , A Mark Richards 1,4, 7 , MD, PhD; and Mark Y Chan 1, 7 MBBS, MHS
1 National University Heart Centre, Cardiac Department, Singapore, Singapore 2 Albert Einstein Hospital, Cardiac Department, Sao Paolo, Brazil 3 Sarawak General Hospital Heart Centre, Cardiac Department, Kuching, Malaysia 4 University of Otago, Cardiac Department, Christchurch,
New Zealand 5 The Chinese University of Hong Kong, Cardiac Department, Shatin, Hong Kong 6 National Heart Centre, Cardiac Department, Singapore, Singapore 7 Yong Loo Lin School of Medicine, Medicine Department, National University of Singapore, Singapore
METHODS
RESULTS Table 1: Baseline characteristics
Fig 4: Difference in Initial Versus Final ASPR and ADPR with Different ADP Receptor Antagonists
Fig 2: Percentage of Patients with High PR on Initial and Final ASPR and ADPR Categorized by ACS Diagnosis and PCI Status
Fig 3: Incidence of IPTE, 30-day MACCE and 12-month MACCE As a Function of High Initial ASPR and ADPR Status
Table 2: Logistic Regression Model for IPTE, 30-Day MACCE and 12-month MACCE Relationship between D2B time and
• PR testing has prognostic value when performed before PCI (initial test)
in patients with ACS, but not after PCI (final test);
• High on-treatment PR is mores closely related to early peri-PCI events than late post-PCI outcomes
• ASPR and ADPR improve significantly during the index hospitalization, regardless of whether PCI was performed or whether low or high
potency ADP receptor antagonists were administered
• Both ADPR and ASPR are related to IPTE but unexpectedly, high ASPR had a stronger association with IPTE than ADPR when both tests were included in the same multivariable model
CONCLUSIONS
ACS subjects
Baseline Characteristics:
Men (n, %) 633 (81.6)* 135 (88.8)* 0.03 435 (83.5) 333 (81.8) 0.5
Body-mass index (kg m-2) 26±4 27±6 0.03 26±4 26±5 0.3
Hypertension 517 (66.6%) 91 (60.0%) 0.10 354 (67.9%)* 254 (62.4%)* 0.08
Dyslipidemia 476 (61.3%)* 70 (46.1%)* <0.001 323 (62.0%)* 254 (62.4%)* 0.03
Current Smoker 422 (54.4%) 82 (53.9%) 0.4 287 (55.1%) 230 (56.5%) 0.7
Diabetes 280 (36.1%)* 51 (33.6%)* 0.5 182 (34.9%) 149 (36.6%) 0.5
Prior congestive heart failure 26 (3.4%) 6 (3.9%) 0.7 17 (3.3%) 15 (3.7%) 0.7
Prior myocardial infarction 227 (30.0%)* 28 (18.4%)* 0.007 149 (28.6%) 105 (25.8%) 0.3
Prior stroke 422 (54.4%) 82 (53.9%) 0.7 20 (3.8%) 22 (5.4%) 0.2
Prior CABG 46 (5.9%) 10 (6.6%) 0.7 30 (5.8%) 26 (6.4%) 0.2
Prior PCI 172 (22.2%) 24 (15.8%) 0.08 114 (21.9%) 82 (20.1%) 0.03
Prior stroke 422 (54.4%) 82 (53.9%) 0.7 20 (3.8%) 22 (5.4%) 0.2
GRACE Score (Mean±SD) 98±29 103±26 0.13 98±28 100±30 0.1
Prior aspirin treatment (>7 days before admission) 266 (34.3%) 40 (26.3%) 0.05 171 (32.8%) 135 (33.2%) 0.8
Prior ADP receptor antagonist treatment 76 (9.8%) 19 (12.5%) 0.30 57 (11.0%) 38 (9.2%) 0.4
STE-ACS 167 (21.5%)* 67 (44.1%)* 0.01 95 (18.2%)* 139 (34.2%)* <0.001
NSTE-ACS 609 (78.5%)* 85 (55.9%)* <0.001 426 (81.8%)* 268 (65.8%)* <0.001
Door to balloon time of STE-ACS patients (Min) 54.9±41.6* 68.9±35.1* 0.05 55.0±49.0 61.6±37.7 0.3
Number of lesions with Stenosis ≥50% 3.3±2.0* 3.0±1.8* 0.06 3.3±2.1 3.3±1.8 0.6
Number of stents implanted per patient 1.6±0.9 1.2±0.5 0.6 1.6±0.9 1.6±0.9 0.8
Peak Troponin I (ng/L) 14.7±22.1* 23.0±26.2* 0.06 11.1±18.0* 23.1±27.4* <0.001
Highest Creatinine Value within 72 Hours (µmol/dL) 115±132 104±77 0.08 107±93 118±149 0.5
Trough Hemoglobin Value within 72 Hours (g/dL) 13.9±1.8 13.8±1.8 0.8 14.2±3.5 14.2±7.2 0.2
Baseline platelet count (×10³ cells per mm³) 238±63 244±71 0.6 229±60* 250±68* <0.001
Platelet Reactivity Tests:
Admission to First PR test (Days) 2.3±2.6* 2.0±2.0* 0.05 2.5±2.5* 2.0±2.6* 0.001
On prasugrel or ticagrelor 126 (16.3%) 39 (23.7%) <0.001 104 (20.0%)* 58 (14.2%)* 0.007
Initial ASPI test (AU*min) 160±70* 492±241* <0.001 166±125* 276±196* <0.001
Initial ADP test (AU*min) 432±274* 785±346* <0.001 263±107* 780±250* <0.001
Initial Platelet Reactivity Test
High initial ASPR
Odds ratio (95% confidence interval) Adjusted for GRACE score 7.46 (2.54−21.90) 1.41 (0.54−3.69) 1.14 (0.63-2.06)
(≥468 AU*min)¶ Adjusted for GRACE score 5.01 (1.38−18.18) 1.381 (0.609-3.133) 0.71 (0.44-1.15) Odds ratio (95% confidence interval) Adjusted for initial ASPR and GRACE score 1.001 (.999-1.003) -
Odds ratio (95% confidence interval)
Odds ratio (95% confidence interval)
Platelet reactivity (PR) testing has prognostic value in patients with
acute coronary syndrome (ACS) undergoing percutaneous
coronary intervention (PCI) There are conflicting data on the
optimal type and timing of PR testing We investigated the
prognostic value of high on-aspirin PR (ASPR) and high on-ADP
receptor antagonist PR (ADPR) in ACS patients on dual antiplatelet
therapy who were managed invasively
We measured ASPR and ADPR using the Multiplate ASPI
(arachidonic acid agonist) and ADP (adenosine diphosphate
agonist) tests respectively, immediately before (initial test) and
24-48 hours after (final test) angiography and PCI All patients were
monitored for intra-procedural thrombotic events (IPTE), in
accordance with the ACUITY definition, 30-day and 12-month
major adverse cardiovascular and cerebrovascular events
(MACCE)
Figure.3
Figure 4
Fig 1: Study Flow
Platelet Reactivity (PR)
Acute Coronary Syndrome (ACS)
Percutaneous Coronary Intervention (PCI)
On-Aspirin PR (ASPR)
On-ADP receptor antagonist PR (ADPR)
Intra-Procedural Thrombotic Events (IPTE)
Major Adverse Cardiovascular and Cerebrovascular
Events (MACCE)
Hazard Ratio (HR)
Dual antiplatelet therapy (DAPT)
Adenosine Diphosphate (ADP)
ABBREVIATIONS
BACKGROUND
Funding source: The study was funded by the National Medical Research Council of Singapore (NMRC/CSA/028/2010) with platelet reactivity analysers and test kits supplied by Roche
Diagnostics (Basel Switzerland) Both sponsors had no role in the study design, site selection, data collection, data analysis, or data interpretation, but Roche Diagnostics had the right to a non-binding review of the manuscript before submission
Disclosures: A/Prof Mark Chan and Professor Mark Richards receive research funding from Roche Diagnostics (Basel Switzerland) and are on the speaker’s bureau of Roche Diagnostics
*P<0.05
Presented at ACC 2016
Trang 11Copyright © 2008 National University Health System
TROPICAL-ACS