Impact of access site on bleeding and ischemic events in patients with non-ST-segment elevation myocardial infarction treated with prasugrel at the time of percutaneous coronary intervention or as pretreatment at the time of diagnosis: the ACCOAST access substudy

1. Impact of access site on bleeding and ischemic events in
patients with non-ST-segment elevation myocardial
infarction treated with prasugrel at the time of
percutaneous coronary intervention or as pretreatment at
the time of diagnosis: the ACCOAST access substudy
Porto I.,1 Bolognese L.,2 Dudek D.,3 Goldstein P.,4 Hamm C.,5 Tanguay J.F.,6 ten Berg J.,7
Widimsky P.,8 Brown E.,9 LeNarz L.,9 Miller D.L.,9 Montalescot G.10 for the ACCOAST
Investigators
1 Interventional Cardiology Unit, San Donato Hospital, Arezzo, Italy 2Cardiovascular and Neurological Department,
Azienda Ospedaliera Arezzo, Arezzo, Italy 3Institute of Cardiology, Jagiellonian University Medical College, University
Hospital, Krakow, Poland 4SAMU and Emergency Department, Lille University Hospital, France 5Kerckhoff Heart and
Thoraxcenter, Bad Nauheim and Medical Clinic I, University of Giessen, Germany 6Montreal Heart Institute,
Université de Montréal, Montreal, Canada 7Department of Cardiology, St. Antonius Hospital, Nieuwegein,
Netherlands 8Third Medical Faculty of Charles University and University Hospital Royal Vineyards, Prague, Czech
Republic 9Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA 10ACTION study group, Institut de
Cardiologie, UPMC Univ Paris, France and Centre Hospitalier Universitaire Pitié-Salpêtriėre (AP-HP), Paris, France
Funding: This work was supported by Daiichi Sankyo Co., Ltd and Eli Lilly and Company.

2. I have no relevant conflict of interest to disclose
related to this presentation

3. Study Design
NSTEMI + Troponin ≥ 1.5 times ULN local lab value
Clopidogrel naive or on long term clopidogrel 75 mg
N=4033
Placebo
Coronary
Angiography
Prasugrel 60 mg
Prasugrel 30 mg
Coronary
Angiography
Prasugrel 30 mg
PCI
PCI
Randomize 1:1
Double-blind
Prasugrel 10 mg or 5 mg (based on weight and age) for 30 days
CABG or
Medical
Management
(no more prasugrel)
CABG or
Medical
Management
(no prasugrel)
1° Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa inh. bailout, at 7 days
Montalescot G et al. Am Heart J 2011;161:650-656.e1

4. Main Inclusion/Exclusion Criteria
Inclusion
• NSTEMI symptoms within 48 hours prior to study entry
• Patient to be scheduled for coronary angiography and PCI within 2 hours to 24 hours of
randomization and no later than 48 hours after randomization
Exclusion
• STEMI patients
• Medical history contraindicating therapy with prasugrel
• History of stroke or transient ischemic attack (TIA)
• LD of any P2Y12 antagonist ≤7 days of study entry

5. Non-CABG TIMI Major Bleeding for
Prespecified Subgroups Through 7 days
Overall (pre-treatment vs. no pre-treatment)
No Pre-tx
n (%)
3318 15 (0.90) 8 (0.48)
1.87 (0.79, 4.42)
715 12 (3.22) 1 (0.29)
11.01 (1.43, 84.70)
2923 12 (0.81) 5 (0.35)
2.32 (0.82, 6.58)
1110 15 (2.72) 4 (0.72)
3.85 (1.28, 11.61)
205 3 (2.91) 1 (0.98)
NE
3824 24 (1.24) 8 (0.42)
2.94 (1.32, 6.55)
NE
820 5 (1.21)
2 (0.49)
3213 22 (1.35) 7 (0.44)
3.09 (1.32, 7.23)
NE
1340 2 (0.29)
2683 25 (1.87) 5.06 (1.94,13.22)
2504
1529
1814
2219
4 (0.62)
5 (0.37)
5 (0.41)
4 (0.52)
3 (0.33)
6 (0.55)
7 (0.62)
2 (0.24)
0 (0.00)
NE
NE
470 7 (2.88) NE
0.2 0.5 1 2 5 10 20 30 40 50 60 70 80 90
PCI
CABG*
Sex
Male
Female
Age
<75 years
>75 years
Weight
<60 kg*
>60 kg
Diabetes
Yes*
No
Tobacco Use
Yes*
No
History of Hypertension
Yes
No*
History of Hypercholesterolemia
Yes
No
Radial*
Prasugrel MD
5 mg*
10 mg
Region
Eastern Europe/Israel
Western Europe/Canada
Pre-tx
n (%)
27 (1.33)
Hazard Ratio
(95% CI)
2.95 (1.39, 6.28)
Total
Patients
4033
2781
Medical Management*
Prior clopidogrel treatment
GRACE score
<140
>140
Pre-treatment better No pre-treatment better
20 (1.43) 2.48 (1.09, 5.62)
238 2 (1.65) NE
1014 5 (0.97) NE
232 1 (0.89) NE
1990 14 (1.37) 3.36 (1.11,10.22)
2008 13 (1.30) 2.62 (0.93, 7.34)
1998 13 (1.31) 3.29 (1.07,10.09)
2003 13 (1.27) 2.49 (0.89, 7.00)
3079 14 (0.91) 2.37 (0.91, 6.15)
852 13 (2.88) 3.83 (1.09, 13.45)
2 (0.88)
2198 7 (0.63) 1.39 (0.44, 4.37)
Access
Femoral
Brachial*
1692
2341
22 (1.72) 4.26 (1.61,11.25)
5 (0.66)
13 (1.42) 4.30 (1.22,15.08)
14 (1.25) 2.28 (0.88, 5.93)
2276 20 (1.75) 2.87 (1.21, 6.78)
1711 6 (0.69)
7 0 (0.00)
Interaction
P-value†
0.29
0.12
0.51
0.99
0.81
0.02
0.15
0.43
0.99
0.72
0.55
0.99
0.38
9 (0.45)
8 (0.58)
1 (0.85)
0 (0.00)
0 (0.00)
4 (0.41)
5 (0.50)
4 (0.40)
5 (0.51)
6 (0.39)
3 (0.75)
5 (0.46)
10 (1.16) 3 (0.36) 3.20 (0.88, 11.62)
17 (1.45) 6 (0.51) 2.84 (1.12, 7.19)
0.88
Yes*
No 3801 26 (1.35) 9 (0.48) 2.83 (1.32, 6.03)
0.75
Time from Sx to LD
<median
>median
Time from first LD to angio/PCI
<median
>median
NE
Montalescot G, et al. N Engl J Med. 2013; 369(11):999-1010

6. Statistical Analysis
• Characteristics of coronary angiography patients with femoral versus radial
access were compared using a chi-square test for categorical variables or analysis
of variance for continuous variables.
• Analyses were conducted for the all patients and the PCI cohort.
• Hazard ratios were estimated using a proportional hazards model comparing
femoral versus radial access for safety/efficacy endpoints. A log-rank statistic was
used to compare access sites.
• Propensity score analyses were conducted using a logistic regression propensity
model with 36 baseline variables to estimate the propensity for femoral access
(propensity score). A proportional hazards model with the access site and
quintile of estimated propensity score was used to estimate the hazard ratio
(femoral vs. radial access) accounting for access selection bias.
• Results were considered statistically significant for p < 0.05 (log-rank statistic).
95% confidence intervals for the hazard ratios were also estimated.

7. Baseline Characteristics – All Patients
Variable
Femoral
(N=2276)
Radial
(N=1711)
p-value
Age ≥75 years, % 18.9 16.0 0.018
Female, % 28.2 26.7 0.28
Eastern Europe, % 40.5 36.7 0.016
CRUSADE score, mean±SDa 35.7±12.0 34.4±12.0 <0.001
GRACE score, mean±SDb 121.9±26.7 119.0±26.8 <0.001
Prior CABG, % 7.4 2.5 <0.001
Prior PCI, % 17.6 14.7 0.014
PPI use at baseline, % 34.9 45.2 <0.001
PPI= proton pump inhibitor. an = 2187 and 1615; bn = 2231 and 1661 for femoral and radial access, respectively.
BMI, weight, and tobacco use p=NS.

8. Baseline Characteristics – PCI Patients
Variable
Femoral
(N=1571)
Radial
(N=1191)
p-value
Age ≥75 years, % 18.2 15.6 0.07
Female, % 25.0 22.6 0.15
Eastern Europe, % 39.6 37.8 0.33
CRUSADE score, mean±SDa 35.0±11.8 33.5±12.0 0.002
GRACE score, mean±SDb 121.6±26.4 118.9±26.7 0.010
Prior CABG, % 7.7 2.4 <0.001
Prior PCI, % 18.9 14.4 0.002
PPI use at baseline, % 35.6 46.6 <0.001
PPI= proton pump inhibitor. an = 1509 and 1131; bn = 1539 and 1162 for femoral and radial access, respectively.

9. Outcomes through 7 Days by Access Site
All Patients
Variable
Femoral (%)
(N=2276)
Radial (%)
(N=1711)
HR (95% CI)
(Femoral/Radial)
p-value
CVD/MI/S/UR/GPIIb/IIIa bailout 10.4 9.3 1.13 (0.92, 1.38) 0.24
CVD 0.4 0.5 0.75 (0.28, 1.99) 0.56
MI 6.2 5.0 1.26 (0.96, 1.65) 0.09
Stroke 0.2 0.7 0.31 (0.11, 0.88) 0.02
UR 1.5 0.8 1.83 (0.98, 3.41) 0.05
GPIIb/IIIa bailout 4.0 3.7 1.09 (0.79, 1.50) 0.61
Abbreviations: CVD = cardiovascular death; MI= myocardial infarction ; S=stroke; UR= urgent revascularization

10. Outcomes through 7 Days by Access Site
PCI Cohort
Variable
Femoral (%)
(N=1571)
Radial (%)
(N=1191)
HR (95% CI)
(Femoral/Radial)
p-value
CVD/MI/S/UR/GPIIb/IIIa bailout 14.1 11.7 1.24 (1.00, 1.53) 0.049
CVD 0.3 0.3 1.26 (0.30, 5.28) 0.75
MI 8.9 6.9 1.31 (0.99, 1.72) 0.05
Stroke 0.2 0.3 0.57 (0.18, 2.54) 0.45
UR 1.9 1.0 1.84 (0.94, 3.60) 0.07
GPIIb/IIIa bailout 5.7 5.0 1.15 (0.83, 1.60) 0.41
Abbreviations: CVD = cardiovascular death; MI= myocardial infarction; S=stroke; UR= urgent revascularization

11. Bleeding measures by access site
Bleeding measure Femoral (%) Radial (%) HR (95% CI)
(Femoral/Radial)
p-value
All Patients (N=2276) (N=1711)
Non-CABG TIMI major 1.2 0.5 2.53 (1.15, 5.58) 0.017
Access-site related 0.6 0.1 4.87 (1.10, 21.59) 0.021
Non-CABG TIMI major or minor 2.8 0.9 3.02 (1.75, 5.23) <0.001
GUSTO severe/life threatening 1.3 1.1 1.25 (0.70, 2.24) 0.45
STEEPLE major 3.4 2.6 1.34 (0.92, 1.94) 0.12
PCI Cohort (N=1571) (N=1191)
Non-CABG TIMI major 1.3 0.4 3.19 (1.20, 8.47) 0.014
All Access-site related 0.7 0.2 4.18 (0.93, 18.84) 0.043
Access-site related with closure device
1.0
(closure device used, n=598)
Non-CABG TIMI major or minor 3.4 0.8 4.60 (2.27, 9.32) <0.001
GUSTO severe/life threatening 0.8 0.3 3.04 (0.86, 10.77) 0.07
STEEPLE major 2.5 0.8 2.98 (1.49, 5.97) 0.001
Access-site related bleeding was as reported by investigator including retroperitoneal for femoral
access

12. Outcomes through 7 Days by Access Site All
Patients (Propensity Score Analysis)
Variable
HR (95% CI)
(Femoral/Radial)
p-value
CVD/MI/S/UR/GPIIb/IIIa bailout 1.12 (0.91, 1.39) 0.28
CVD 0.79 (0.27, 2.35) 0.67
MI 1.23 (0.93, 1.62) 0.16
Stroke 0.35 (0.12, 1.04) 0.06
UR 2.04 (1.05, 3.96) 0.036
GPIIb/IIIa bailout 1.06 (0.76, 1.48) 0.74
Abbreviations: CVD = cardiovascular death; MI= myocardial infarction ; S=stroke; UR= urgent
revascularization

13. Outcomes through 7 Days by Access Site PCI
Cohort (Propensity Score Analysis)
Variable
HR (95% CI)
(Femoral/Radial)
p-value
CVD/MI/S/UR/GPIIb/IIIa bailout 1.21 (0.97, 1.51) 0.10
CVD 0.98 (0.22, 4.32) 0.98
MI 1.27 (0.95, 1.69) 0.11
Stroke 0.58 (0.12, 2.77) 0.49
UR 2.17 (1.05, 4.50) 0.037
GPIIb/IIIa bailout 1.11 (0.79, 1.57) 0.55
Abbreviations: CVD = cardiovascular death; MI= myocardial infarction; S=stroke; UR= urgent
revascularization

14. Propensity score analysis of bleeding endpoints
Bleeding measure HR (95% CI)
(Femoral/radial)
aAll patients, femoral access N= 2276, radial access N=1711.
bPCI cohort, femoral access N=1571, radial access N=1191.
p-value
All Patientsa
Non-CABG TIMI major 2.24 (1.00, 5.02) 0.0495
Non-CABG TIMI major or minor 3.25 (1.80, 5.88) <0.001
GUSTO severe/life threatening 1.45 (0.77, 2.71) 0.25
STEEPLE major 1.40 (0.94, 2.07) 0.10
PCI Cohortb
Non-CABG TIMI major 2.25 (0.84, 6.06) 0.11
Non-CABG TIMI major or minor 3.96 (1.93, 8.12) <0.001
GUSTO severe/life threatening 2.07 (0.58, 7.40) 0.26
STEEPLE major 2.46 (1.21, 5.03) 0.014

15. Summary
• Patients who received radial access in the overall cohort were
younger, less often from Eastern Europe, and had lower GRACE and
CRUSADE bleeding risk scores.
• PCI patients who received radial access had lower GRACE and
CRUSADE scores.
• For the PCI cohort, the hazard rate through 7 days for the primary
composite endpoint and for all non-CABG TIMI major bleeding were
significantly lower in patients who received radial access.
• In propensity adjusted analyses for all patients and for the PCI cohort,
hazard rates for non-CABG TIMI major bleeding did not favor radial
versus femoral access.

16. Conclusions
For PCI patients, femoral access was associated
with significantly more TIMI major bleeds,
however, the effect was attenuated after
propensity modeling.