Online Appendix for the following JACC article
TITLE: Impact of Platelet Reactivity on Clinical Outcomes After Percutaneous Coronary
Intervention: Collaborative Meta-Analysis of Individual Participant Data
AUTHORS: Somjot S. Brar, MD, MPH, Jurrien ten Berg, MD, PHD, Rossella Marcucci, MD,
Matthew J. Price, MD, Marco Valgimigli, MD, PHD, Hyo-Soo Kim, MD, PHD, Giuseppe Patti,
MD, Nicoline J. Breet, Germano DiSciascio, MD, Thomas Cuisset, MD, PHD, George Dangas,
MD, PHD
APPENDIX
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Supplementary Figure 1. Funnel Plot of Precision by the Mantel-Haenzel (MH) Log Risk
Ratio
2
Supplementary Figure 2. Kaplan-Meier Failure Rate in the Derivation Dataset
Red line represents subjects with high on-treatment platelet reactivity (P2Y12 reaction units
[PRU] ≥231). Blue line represents subjects with PRU <231. The event rate was 14.1% for
subjects with high on-treatment platelet reactivity compared to 7.1% below the cutoff (log-rank p
= 0.0001).
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Supplementary Figure 3. Kaplan-Meier Failure Rate in the Validation Dataset
Red line represents subjects with high on-treatment platelet reactivity (P2Y12 reaction units
[PRU] ≥231). Blue line represents subjects with PRU <231. The event rate was 14.8% in
subjects with high on-treatment platelet reactivity compared to 7.3% below the cutoff (log-rank p
= 0.0002).
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Supplementary Table 1. P2Y12 Reaction Units Threshold and Long-Term Outcomes
PRU threshold
Derivation Cohort
231*
Validation Cohort
231**
Full Cohort
230
Kaplan-Meier estimates
Log-rank test
14.1% vs. 7.1%
0.0001
14.8% vs. 7.3%
0.0002
14.7% vs. 7.0%
<0.001
HR (95% CI)
p value
2.07 (1.50–2.86)
<0.001
2.00 (1.36–2.94)
<0.001
2.13 (1.64–2.77)
<0.001
*Bootstrapping (with replacement), 100 replications. **Value determined from derivation cohort bootstrap analysis.
CI = confidence interval; HR = hazard ratio.
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Additional Analyses:
1) Net reclassification improvement (NRI)
2) Integrated discrimination improvement (IDI)
The increased discriminative value of platelet function testing was further examined using net
reclassification improvement. This method is based upon the difference between two models in
the individual estimated probability that a case subject will be categorized as a case subject.
We calculated predicted probabilities for the outcome of death, myocardial infarction, and stent
thrombosis for individual patients and predetermined these probabilities after adding P2Y12
reaction units to the model. The net reclassification improvement was calculated by assessing the
net improvement in risk classification. This method requires that there exist a priori risk
categories. In the absence of well-established risk categories, we have used 0% to 4%, 5% to
10%, and >10% for the risk of the composite endpoint. The base model included age, sex,
hypertension, diabetes, dyslipidemia, and smoking status.
Reclassification for participants who experienced an event (death, myocardial infarction, or stent
thrombosis) and for those who did not have an event is summarized in the following tables.
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Supplementary Table 1. The P2Y12 Reaction Units [PRU] Variable Was Dichotomized at
230
-------------------------------------Without
|
Platelet | With Platelet Function
Function |
Testing
Testing
|
|
<5% 5-10% >=10% Total
----------+--------------------------Event
|
<5% |
4
2
6
5-10% |
27
99
75
201
>=10% |
10
10
20
|
Total |
31
111
85
227
----------+--------------------------No event |
<5% |
58
17
75
5-10% |
665 1,339
596 2,600
>=10% |
86
65
151
|
Total |
723 1,442
661 2,826
--------------------------------------
In patients with events:
37.2% were reclassified upward
16.7% were reclassified downward
In patients without events:
22.9% were reclassified upward
27.3% were reclassified downward
The net reclassification improvement was 0.23 (or 23%) (p < 0 .001).
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Supplementary Table 2. The P2Y12 Reaction Units [PRU] Variable Was Defined
According to Quartiles of PRU Values
-------------------------------------Without
|
Platelet | With Platelet Function
Function |
Testing
Testing
|
|
<5% 5-10% >=10% Total
----------+--------------------------Event
|
<5% |
4
2
6
5-10% |
27
109
65
201
>=10% |
8
12
20
|
Total |
31
119
77
227
----------+--------------------------No event |
<5% |
50
24
74
5-10% |
716 1,362
508 2,586
>=10% |
73
76
149
|
Total |
766 1,459
584 2,809
--------------------------------------
The net reclassification improvement was 0.23 (p < 0 .001).
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Supplementary Table 3. The P2Y12 Reaction Units [PRU] Variable Is Defined as
Continuous Values of PRU
-------------------------------------Without
|
Platelet | With Platelet Function
Function |
Testing
Testing
|
|
<5% 5-10% >=10% Total
----------+--------------------------Event
|
<5% |
4
2
6
5-10% |
20
131
50
201
>=10% |
1
5
14
20
|
Total |
25
138
64
227
----------+--------------------------No event |
<5% |
50
24
74
5-10% |
507 1,682
397 2,586
>=10% |
2
72
75
149
|
Total |
559 1,778
472 2,809
--------------------------------------
The net reclassification improvement was 0.18 (p < 0.001).
The integrated discrimination improvement (IDI) was also calculated. The values for the various
PRU variables were:
 PRU dichotomized at 230: IDI = 0.010 (p < 0.001)
 PRU as quartiles: IDI = 0.010 (p < 0.001)
 PRU as a continuous variable: IDI = 0.008 (p < 0.001)
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