1. Gender Differences in Outcomes Following Percutaneous Coronary Intervention of Patients with Non-ST elevation Acute Coronary Syndrome A Substudy of the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial
Ken Mori1, Alexandra J. Lansky1, Ricardo A. Costa1, Angel Cequier2, Charles V. Pollack, Jr.3, James Hoekstra4, Michel Bertrand5, Bernard Gersh6, Gregg W. Stone1
Control/Tracking Number: 06-A-2771-CRF Activity: Abstracts Current Date/Time: 6/13/2006 5:44:19 PM Gender Differences in Outcomes Following Percutaneous Coronary Intervention of Patients with Non-ST elevation Acute Coronary Syndrome: A Substudy of the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial. Author Block: Ken Mori1, Alexandra J. Lansky1, Ricardo A. Costa1, Angel Cequier2, Charles V. Pollack, Jr.3, James Hoekstra4, Michel Bertrand5, Bernard Gersh6, Gregg W. Stone1 1Cardiovascular Research Foundation, New York, NY;2Bellvitge University Hospital, Barcelona, Spain3Duke University Medical Center, Durham, NC;4Wake Forest University School of Medicine, Winston-Salem, NC;5Hospital Cardiologique, Lambersart, France6Mayo Clinic College of Medicine, Rochester, MN Background: Women with NSTE-ACS undergoing PCI are at higher risk of in-hospital mortality and bleeding complications compared to men. The purpose of this analysis is to evaluate the outcome of women compared to men in the ACUITY Trial.
Methods: The ACUITY trial randomized 13,819 pts with moderate to high risk ACS to unfractionated heparin or enoxaparin + GPI, versus bivalirudin + GPI, versus bivalirudin alone. We compare the net clinical outcomes (death, MI, revascularization and major bleeding) and the ischemic outcomes (death, MI, revasc) of men (n=5698) and women (n=2091) undergoing PCI.
Results: Women were older (men 61.5±11.3 vs. women 65.9±11.6yrs , P<0.0001), had more renal insufficiency (13.9 vs. 30.9%, P<0.001), diabetes (25.1 vs. 34.5%, P<0.0001) and hypertension (62.1 vs. 74.8%, P<0.0001), less prior MI (32.0 vs. 26.2%, P<0.0001) and CABG (19.1 vs. 13.1%, P<0.0001), and less smoking (32.4 vs. 26.9%, P<0.0001) compared to men. Women showed significant delays to treatment compared to men. Clinical outcomes at 30 days in are in the Table. Conclusions: Despite being older, having more co-morbidities and treatment delays, women with NSTE-ACS who were treated with contemporary PCI in ACUITY had similar favorable ischemic event rates compared to men. However, the overall major bleeding complications remain significantly higher in women compared to men.
Clinical outcomes at 30 days
Variable Men, N=5698 Women, N=2091 P Value
Net clinical outcome (Composite ischemia and Major bleeding) 671 (11.8%) 362 (17.3%) <0.0001
Composite ischemia (8.7%) 190 (9.1%)
-Death (any cause) (1.1%) 21 (1.0%)
-MI (6.0%) 141 (6.7%)
-Q-Wave (1.1%) 20 (1.0%)
-Non Q-Wave (5.0%) 122 (5.8%)
-Unplanned revasc (3.4%) 66 (3.2%)
Major bleeding (Non-CABG) (4.2%) 223 (10.7%) < Author Disclosure Block:  K. Mori, None.
Category (Complete):  47. Women’s Health Care Presentation Format (Complete):  E-Poster Keyword (Complete):  Randomized Clinical Trials ; Women's Health Issues ; Acute Coronary Syndromes Status: Complete
1Cardiovascular Research Foundation, New York, NY;
2Bellvitge University Hospital, Barcelona, Spain
3Duke University Medical Center, Durham, NC;
4Wake Forest University School of Medicine, Winston-Salem, NC;
5Hospital Cardiologique, Lambersart, France
6Mayo Clinic College of Medicine, Rochester, MN

2. Background
Women are at increased risk for vascular complications compared to men.
(Leslie Cho, et al, JACC 2000;36: 381-6)
Bivalirudin with provisional GPIIb/IIIa inhibitor is not inferior to heparin with planned GPIIb/IIIa inhibitor during contemporary PCI with regard to suppression of acute ischemic complications, and is associated with less bleeding.
(A.Michael Lincoff, et al, JAMA 2003;289: )
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3. ACUITY Trial Design
Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,800)
UFH or
Enoxaparin
+ GP IIb/IIIa
Bivalirudin
Alone R*
Angiography within 72h
Medical
management
PCI
CABG
Moderate-
high risk
ACS
Aspirin in all
Clopidogrel
dosing and timing
per local practice
*Stratified by pre-angiography thienopyridine use or administration
ACUITY Design. Stone GW et al. AHJ 2004;148:764–75

4. Major entry criteria Inclusion Criteria Exclusion Criteria
Moderate-high risk unstable angina or NSTEMI
Inclusion Criteria
Age ≥18 years
Chest pain ≥10’ within 24h
At least one of:
New ST depression or transient ST elevation ≥1 mm
Troponin I, T, or CKMB
Documented CAD
All other 4 TIMI risk criteria
Age ≥65 years
Aspirin within 7 days
≥2 angina episodes w/i 24h
≥3 cardiac risk factors
Written informed consent
Exclusion Criteria
No angiography within 72h
Acute STEMI or shock
Bleeding diathesis or major bleed within 2 weeks
Platelet count ≤100,000/mm3
INR >1.5 control
CrCl ≤30 ml/min
Abcx or ≥2 prior LMWH doses
Prior UFH, LMWH (1 dose), eptifibatide and tirofiban were allowed
Allergy to drugs, contrast
ACUITY Design. Stone GW et al. AHJ 2004;148:764–75

5. ACUITY Primary Results (ITT)
Heparin* + IIb/IIIa vs. Bivalirudin + IIb/IIIa vs. Bivalirudin Alone
PNI <0.001
PSup = 0.015
PNI = 0.011
PSup = 0.32
PSup <0.001
*Heparin=unfractionated or enoxaparin

6. Non CABG Major bleeding definitions for ACUITY
Intracranial bleeding
Intraocular bleeding
Access site hemorrhage requiring intervention
≥5 cm diameter hematoma
Reduction in hemoglobin concentration of ≥4g/dL without an overt source of bleeding
Reduction in hemoglobin concentration of ≥3 g/dL with an overt source of bleeding
Re-operation for bleeding
Use of any blood product transfusion

7. ACUITY Major Bleeding Endpoints
Heparin* + IIb/IIIa vs. Bivalirudin + IIb/IIIa vs. Bivalirudin Alone
PSup=0.31
PSup0.001
PSup=0.38
PSup<0.001
All Major Bleeding
(All, including CABG)
Major Bleeding
(Non-CABG related)
*Heparin=unfractionated or enoxaparin

8. Current Analysis Objective: Methods:
The purpose of this analysis is to evaluate the outcome of women compared to men with acute coronary syndrome undergoing PCI in the ACUITY trial.
Methods:
Comparison of clinical presentation at baseline, angiographic characteristics and outcomes at 30 days in men vs. women with ACS who underwent PCI
13819 ACS patients (4157 female/ 9662 male)
7789 underwent PCI (2091 female/5698 male)

9. All patients (including PCI, CABG and medication patients)

10. Baseline Clinical Characteristics
All patients
N=13819
FEMALE
N=4157
MALE
N=9662
P value
Age, years
65.1 ±11.8
61.5 ±11.4
<0.0001
Diabetes, %
32.6
26.2
Hypertension, %
73.8
64.1
Current Smoker, %
24.5
31.1
Previous MI, %
33.5
Previous PCI, %
36.4
39.9
0.0001
Previous CABG, %
13.2
19.9
Renal insufficiency*, %
30.0
14.4
Previous use of Thienopyridine, %
62.3
64.6
0.009
CKMB/Troponin elevation, %
56.1
60.8
Women were older, more frequent DM, HT , current HL renal insufficiency.
*Defined as creatinine clearance < 60 mL/min.

11. Angiographic Characteristics
All QCA Patients
N=6921
FEMALE
N=2274
MALE
N=4647
P value
Jeopardy Score
1.9±2.6
2.6±2.8
<0.0001
Ejection Fraction, %
66.1±11.7
63.2±12.3
TIMI Flow Grade, %
- 0/1
6.2
9.7
- 2
2.8
5.9
- 3
90.9
84.3
Myocardial Blush Grade, %
9.8
10.2
13.9
83.6
76.2
Women were older, more frequent DM, HT , current HL renal insufficiency.

12. Angiographic Characteristics
All QCA Patients
N=6921
FEMALE
N=2274
MALE
N=4647
P value
Lesions / pts
3.4±2.7
4.4±3.0
<0.0001
# of diseased vessel, %
- 0VD
14.7
6.6
- 1VD
23.4
16.0
- 2VD
27.7
28.2
0.67
- 3VD
34.1
49.1
Extent of disease, mm
36.0±28.2
41.8±30.8
Lesion Location, %
- LAD
67.6
78.1
- RCA
59.5
72.7
- LCX
54.0
69.0
Women were older, more frequent DM, HT , current HL renal insufficiency.

13. 30-day Clinical events in all Patients
(%)
p<0.0001 15
Female
13.1
Male
10.4
P=0.06 10
p<0.0001
7.9
7.6
7.0
P=0.28
5.2
4.8
P=0.10 5
P=0.29
3.4
2.6
2.1
1.6
1.3
Composite
Ischemia
Ischemic
revascularization
Major
bleeding
Net Clinical
Events
Death MI

14. PCI patients

15. ACUITY Trial in PCI patients
Unstable angina or non ST-segment elevation MI (n=7789)
Prospect, randomized, multi-center trial
ASA + clopidogrel (theinopyridine dosing and timing pre local practice)
Angioplasty within 72 hours
UFH or Enoxaparin + GPI
Bivalirudin + GPI
Bivalirudin
Women
N=1110, Lesion=1447
Men
N=2554, Lesion=3466
30-day endpoints
Composite ischemia (Death, MI and ischemic revascularization)
Net clinical outcomes (Composite ischemia and Major bleeding)

16. PCI Patients Characteristics
FEMALE
MALE
P value
Age, years
65.9 ±11.6
61.5 ±11.3
<0.0001
Diabetes, %
34.5
25.1
Hypertension, %
74.8
62.1
Current Smoker, %
26.9
32.4
Previous MI, %
26.2
32.0
Previous PCI, %
37.7
39.0
0.26
Previous CABG, %
13.1
19.1
Renal insufficiency*, %
30.9
13.9
Women were older, more frequent DM, HT , current HL renal insufficiency.
*Defined as creatinine clearance < 60 mL/min.

17. Angiographic Characteristics
PCI QCA Patients
N=3664
FEMALE
N=1110
MALE
N=2554
P value
Lesions / pts
3.9±2.4
4.5±2.7
<0.0001
# of diseased vessel, %
- 1VD
24.0
16.8
- 2VD
35.4
33.1
0.17
- 3VD
39.6
49.8
Extent of disease, mm
36.4±25.2
40.6±27.1
Lesion Location, %
- LAD
78.2
81.5
0.0197
- RCA
72.4
77.1
0.0027
- LCX
63.1
73.7
Jeopardy Score
2.4±2.3
2.7±2.3
0.0001
Ejection fraction, %
65.2±12.1
63.2±12.2
0.0002
Women were older, more frequent DM, HT , current HL renal insufficiency.

18. Target vessel FEMALE MALE P value Target Vessel, % - LAD 36.5 33.9
0.08
- RCA
35.9
33.5
0.11
- LCX
27.6
32.6
0.0006
- SVG
5.2
9.0
<0.0001
- IMA
0.3
0.92
Women were older, more frequent DM, HT , current HL renal insufficiency.

19. PCI lesion Characteristics
FEMALE
MALE
P value
TIMI flow, %
- 0/1
10.7
13.1
0.0188
- 2
7.7
10.3
0.0051
- 3
81.6
76.6
0.0001
Myocardial blush grade, %
13.0
16.6
0.0026
15.3
15.8
0.68
71.8
67.6
0.0074
Women were older, more frequent DM, HT , current HL renal insufficiency.

20. PCI lesion Characteristics
FEMALE
MALE
P value
Lesion Morphology, %
Thrombus
13.2
15.6
0.0349
Eccentric
21.8
20.6
0.33
Ulcerated
3.9
5.0
0.09
Aneurysm
0.9
1.5
Ectasia
4.9
6.2
Calcium
- Moderate
19.9
21.9
0.13
- Severe
3.5
0.99
ACC/AHA B2/C, %
55.2
60.7
0.0003
Women were older, more frequent DM, HT , current HL renal insufficiency.

21. QCA method In-Stent Analysis Segment In-stent Proximal Distal Edge
5 mm
In-Stent
5 mm
Proximal
Edge
Distal
Edge

22. QCA results FEMALE MALE P value Pre Procedure RVD, mm 2.7 ± 0.5
2.8 ±0.6
<0.0001
MLD , mm
0.7 ± 0.5
0.57
% DS
72.9 ± 15.8
73.9 ± 15.8
0.06
Lesion length, mm
14.8 ± 9.4
16.0 ± 10.3
Post procedure
In-segment
MLD, mm
2.3 ± 0.5
2.3 ± 0.6
%DS
15.1 ± 10.2
15.2 ± 10.7
0.84
Acute gain, mm
1.5 ± 0.6
1.6 ± 0.6
In-stent
2.6 ± 0.5
16.6 ± 11.1
17.4 ± 11.8
0.08
1.9 ± 0.5
2.0 ± 0.6
0.0001
Women were older, more frequent DM, HT , current HL renal insufficiency.

23. Post procedural morphology
FEMALE
MALE
P value
TIMI flow, %
- 0/1
1.3
1.4
0.65
- 2
1.0
2.3
0.002
- 3
97.8
96.3
0.008
Myocardial blush grade, %
1.8
2.5
0.17
9.1
11.4
0.028
89.1
86.1
0.009
Morphology
Thrombus, %
0.4
0.044
No reflow, %
0.2
0.1
0.27
Dissection, %
0.6
0.83
Distal embolization, %
0.7
0.5
0.47
Women were older, more frequent DM, HT , current HL renal insufficiency.

24. 30-day clinical outcomes in PCI patients
(%)
Female N=2091
17.3
Male N=5698 15
p=0.55
p<0.0001
11.7
10.5 10
9.1
8.7
P=0.25
6.7
6.0
p=0.54
p=0.71
4.2 5
3.5
3.2
1.0
1.1
Net Clinical
Outcomes
Death MI
Composite
Ischemia
Ischemic
revascularization
Major
bleeding
Composite ischemia is defined as death, MI and ischemic revascularization.
Net clinical outcome is defined as composite ischemia and major bleeding.

25. Bleeding complications
FEMALE
MALE
P value
Major bleeding, %
10.7
4.2
<0.0001
Intracranial bleeding, %
0.0
0.80
Access site bleeding, %
1.3
0.3
Hematoma ≥5cm diameter, %
3.8
1.7
Hb≥4g/dL fall without overt source , %
1.9
0.7
Hb≥3g/dL fall with overt source , %
1.6
Re-operation for bleeding , %
0.1
0.75
Blood product transfusion , %
6.0
Major bleeding (ACUITY scale)
Intracranial bleeding
intraocular bleeding
access site hemorrhage requiring intervention
≥5 cm diameter hematoma
reduction in hemoglobin concentration of ≥4g/dL without an overt source of bleeding
reduction in hemoglobin concentration of ≥3 g/dL with an overt source of bleeding
reoperation for bleeding
use of any blood product transfusion
Intracranial, intraocular, or retroperitoneal bleeding
Access site bleed requiring intervention/surgery
Hematoma ≥5 cm
Hgb ≥4g/dL w/o overt source
Hgb ≥3g/dL with an overt source
Reoperation for bleeding
Any blood transfusion

26. Non-CABG Bleeding in Women undergoing PCI
Heparin + IIb/IIIa vs. Bivalirudin Alone
P< 0.001
P=0.002
P<0.001
P=0.07

27. Conclusions
Women with ACS undergoing primary PCI showed similar 30-day composite ischemic complications compared to men, despite being older, and having more co-morbidites.
Women had statistically significant increase in major bleeding complications compared to men.
Bivalirudin alone as compared to Heparin + IIb/IIIa provided significant bleeding advantage in women undergoing PCI.
Women with ACS were older, with more diabetes, hypertension, chronic renal insufficiency and low ejection fraction, but more normal epicardial flow (TIMI 3) and fewer lesions per patient compared to men.
Major bleeding complications increased with increasing age in both women and men.