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Moderate and high risk ACS (n=13,819) Study Design – First Randomization Angiography within 72h Aspirin in all Clopidogrel dosing and timing per local practice Aspirin in all Clopidogrel dosing and timing per local practice UFH/Enox + GP IIb/IIIa (n=4,603) Bivalirudin + GP IIb/IIIa (n=4,604) Bivalirudin Alone (n=4,612) R* *Stratified by pre-angiography thienopyridine use or administration Moderate and high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819) Medical management PCI CABG
Citation preview
Gender Differences in Long-Term Outcomes Following PCI of Patients with Non-ST
Elevation ACS: Results from the ACUITY Trial
Alexandra J. Lansky on behalf of the ACUITY Investigators
Disclosures Alexandra J. Lansky
• Insert disclosures here
Moderateand highrisk ACS
(n=13,819)
Study Design – First Randomization
Ang
iogr
aphy
with
in 7
2h
Aspirin in allClopidogrel
dosing and timingper local practice
UFH/Enox+ GP IIb/IIIa(n=4,603)
Bivalirudin+ GP IIb/IIIa(n=4,604)
BivalirudinAlone
(n=4,612)
R*
*Stratified by pre-angiography thienopyridine use or administration
Moderate and high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819)
Medicalmanagement
PCI
CABG
Study Design – Second Randomization
UFH/Enox+ GP IIb/IIIa
(N=4,603)
Bivalirudin+ GP IIb/IIIa
(N=4,604)
BivalirudinAlone
(N=4,612)
R*
Moderate and high risk unstable angina or NSTEMI undergoing an invasive strategy
GPI upstream (N=2294)
GPI CCL for PCI (N=2309)
GPI upstream (N=2311)
GPI CCL for PCI (N=2293)
Aspirin in allClopidogrel
dosing and timingper local practice
*Stratified by pre-angiography thienopyridine use or administration
Moderateand highrisk ACS
(n=13,819)
Management Strategy (N=13,819)
56.4%
11.4%32.2%CABG (n=1,539)
Medical Rx (n=4,491)
PCI (n=7,789)
Heparin + IIb/IIIaN = 2,561
Bivalirudin + IIb/IIIaN = 2,609
Bivalirudin aloneN = 2,619
UF Heparin Enoxaparin BivalirudinU/Kg mg/Kg mg/kg
Bolus 60 1.0 sc bid 0.1 ivInfusion/h 121 0.25 iv
PCIACT
200-250s0.30 iv bolus2
0.75 iv bolus3
0.50 bolus iv1.75/h infusion iv4
CABG Per institution Per institution Per institution5
Medical mgt None6 None6 None6
Study Medications Anti-thrombin agents (started pre angiography)
1 Target aPTT 50-75 seconds2 If last enoxaparin dose ≥8h - <16h before PCI; 3 If maintenance dose discontinued or ≥16h from last dose4 Discontinued at end of PCI with option to continue at 0.25mg/kg for 4-12h if GPIIb/IIIa inhibitor not used5 Bivalirudin option for off-pump same as PCI dose. For on-pump bivalirudin discontinued 2 hours before6 Option to continue with pre-PCI anti-thrombotic regimen at physician discretion
3 Primary Endpoints (at 30 Days) Composite ischemia
Death, MI, or unplanned revascularization for ischemia Major bleeding (non-CABG)
Intracranial bleeding or intraocular bleeding Retroperitoneal bleeding Access site bleed requiring intervention/surgery Hematoma ≥5 cm Hgb ≥3g/dL with an overt source or ≥4g/dL w/o overt source Blood product transfusion Reoperation for bleeding
Net clinical outcome composite ischemia or major bleeding
Background Women with non-ST elevation acute coronary
syndromes are at increased risk for ischemic and bleeding complications compared to men, especially among those undergoing PCI.
In the ACUITY Trial, women undergoing PCI had similar ischemic event rates but significantly higher major bleeding complications compared to men at 30 days.
Among women, treatment with bivalirudin resulted in significantly less major bleeding and similar ischemic outcomes at 30 days compared with heparin + GP IIb/IIIa inhibitors
Objectives
To examine the impact of gender and antithrombotic therapy on early and late outcomes in patients with moderate and high risk ACS undergoing PCI in the ACUITY Trial
We evaluated 30-day non-CABG Major Bleeding and 1-year Composite Ischemia and Mortality among: Male vs female patients undergoing PCI Female patients undergoing PCI and being treated with
bivalirudin ± GP IIb/IIIa inhibition vs heparin plus GP IIb/IIIa inhibition
Baseline Characteristics by GenderMales vs. FemalesWomen
(N=2091)Men
(N=5698) P-value
Age (median [range], yrs) 67 (25-95) 61 (20-93) <0.0001 Weight (median [IQR], kg) 75 (65, 87) 86 (78, 98) <0.0001Diabetes 34.5% 25.1% <0.0001Hypertension 74.8% 62.1% <0.0001Hyperlipidemia 59.1% 55.0% 0.002Current smoker 26.9% 32.4% <0.0001Prior MI 26.2% 32.0% <0.0001Prior PCI 37.7% 39.0% 0.27Prior CABG 13.1% 19.1% <0.0001Renal insufficiency* 31.0% 13.9% <0.0001Anemia† 19.5% 14.4% <0.0001
*Calculated creatinine clearance <60 mL/min using the Cockcroft-Gault equation.†Anemia was defined using the World Health Organization criteria (Hemoglobin ≤13 g/dL for men and ≤12 g/dL for women).
Clinical Outcomes by GenderMales vs. Females
Women(N=2091)
Men(N=5698) P-value
30-Day Major Bleeding 10.7% 4.2% <0.0001
1-Year Composite Ischemia 19.6% 18.5% 0.27
1-Year Mortality 3.5% 3.1% 0.31
Baseline Characteristics – Female PCI ptsHeparin + IIb/IIIa(N=701)
Bivalirudin + IIb/IIIa(N=690)
Bivalirudin alone
(N=700)Age (median [range], yrs) 68 [25, 91] 67 [37, 95] 66 [34, 92]Weight (median [IQR], kg) 74 [64, 88] 74 [65, 86] 76 [65, 88]Diabetes 36.1% 33.2% 34.1%Hypertension 73.7% 77.7% 73.1%Hyperlipidemia 57.6% 62.9% 56.8%Current smoker 27.4% 26.7% 26.5%Prior MI 23.9% 28.9% 25.8%Prior PCI 36.3% 38.0% 38.6%Prior CABG 13.3% 13.3% 12.8%Renal insufficiency* 5.5% 5.6% 5.5%Anemia† 17.8% 18.3% 18.9%
*Calculated creatinine clearance <60 mL/min using the Cockcroft-Gault equation.†Anemia was defined using the World Health Organization criteria (Hemoglobin ≤13 g/dL for men and ≤12 g/dL for women).
Baseline High Risk Features – Female PCI pts
Heparin + IIb/IIIa(N=701)
Bivalirudin + IIb/IIIa
(N=690)
Bivalirudin
alone(N=700)
Cardiac biomarker (MB or trop) 62.6% 61.7% 64.5%
- Troponin 63.5% 62.3% 65.6%
ST-segment ≥1mm 74.1% 68.3% 72.9%
Cardiac biomarker or ST-segments 75.2% 71.6% 74.4%
TIMI Risk Score
0-2 11.9% 11.1% 10.2%
3-4 50.6% 52.9% 54.7%
5-7 37.5% 36.0% 35.1%
Antiplatelet Medications – Female PCI pts
Heparin + IIb/IIIa(N=701)
Bivalirudin + IIb/IIIa
(N=690)
Bivalirudin alone
(N=700)
Aspirin use or administration pre-angiography or PCI
- Yes 97.9% 97.4% 98.0%
Thienopyridine use or administration pre PCI
- Yes 66.0% 66.7% 67.4%
- Clopidogrel 65.2% 66.6% 67.1%
- Ticlopidine 1.0% 0.9% 0.9%
Procedural Characteristics – Female PCI ptsHeparin + IIb/IIIa(N=701)
Bivalirudin + IIb/IIIa
(N=690)
Bivalirudin alone
(N=700)
Attempted lesions per pt 1.47 ± 0.81 1.43 ± 0.77 1.42 ± 0.71
- 1 65.7% 67.3% 68.8%
- 2 25.2% 25.8% 22.4%
- ≥3 9.1% 6.8% 8.9%
Attempted vessels per pt 1.18 ± 0.45 1.16 ± 0.41 1.15 ± 0.38
- ≥2 15.4% 14.9% 14.3%Target Vessel - Left main 1.2% 0.8% 1.4% - LAD 39.8% 40.1% 39.8% - LCX 27.6% 26.3% 27.0% - RCA 31.4% 32.9% 31.8%
Device Use – Female PCI pts Heparin
+ IIb/IIIa(N=701)
Bivalirudin + IIb/IIIa
(N=690)
Bivalirudin
alone(N=700)
Stent implanted 94.7% 95.8% 95.3%Drug-eluting stents 62.8% 62.2% 61.2% - ≥1 Cypher implanted 42.5% 43.2% 41.5% - ≥1 Taxus implanted 48.2% 48.1% 50.2% - ≥1 other DES implanted 6.8% 8.9% 6.6%Non-drug-eluting stent 31.9% 33.6% 34.1%Thrombectomy 1.7% 0.7% 1.4%Distal Protection 1.1% 1.5% 1.1%Atherectomy 0.7% 0.9% 0.3%Cutting Balloon 3.0% 4.4% 3.0%
1-Year Composite Ischemia – Female PCI pts
*Heparin=unfractionated or enoxaparin
Heparin* + IIb/IIIa vs. Bivalirudin + IIb/IIIa vs. Bivalirudin Alone
0 30 60 90 120 150 180 210 240 270 300 330 360 3950
5
15
25
10
20
UFH/Enox + GP IIb/IIIaBivalirudin + GP IIb/IIIa
Bivalirudin alone
p=0.18
Mor
talit
y (%
)
Days from Randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 3950
1
3
5
2
4
UFH/Enox + GP IIb/IIIaBivalirudin + GP IIb/IIIa
Bivalirudin alone
p=0.23
Mor
talit
y (%
)
Days from Randomization
1-Year Mortality – Female PCI pts
*Heparin=unfractionated or enoxaparin
Heparin* + IIb/IIIa vs. Bivalirudin + IIb/IIIa vs. Bivalirudin Alone
30-Day Major Bleeding (non-CABG) – Female PCI pts
Heparin + IIb/IIIa(N=701)
Bivalirudin + IIb/IIIa
(N=690)
Bivalirudin
alone(N=700)
P value*
Major bleeding 11.8% 13.9% 6.3% <0.001 Intracranial 0% 0% (1) 0% 1.00 Retroperitoneal 1.9% 1.9% 0.3% 0.004 Access site 5.7% 5.9% 1.9% <0.001
- req interv/surgery 1.3% 1.7% 0.9% 0.44- hematoma ≥5 cm 5.0% 4.8% 1.6% <0.001
Hgb ≥3 g/dL with overt source 5.6% 5.4% 1.7% <0.0001
Hgb ≥4 g/dL with no overt source 1.4% 2.5% 1.7% 0.66
Blood transfusion 6.1% 8.1% 3.7% 0.04 Reoperation for bleed 0% 0.1% 0.1% 0.32
*P value for bivalirudin alone vs. heparin + IIb/IIIa inhibitor
Bleeding Endpoints – Female PCI ptsHeparin + IIb/IIIa(N=701)
Bivalirudin + IIb/IIIa
(N=690)
Bivalirudin
alone(N=700)
PValue
ACUITY Scale - Major Bleed, all 12.1% 14.1% 6.9% <0.001
- Major, non-CABG 11.8% 13.9% 6.3% <0.001
- Minor, non-CABG 32.5% 34.2% 17.1% <0.001
TIMI Scale - Any 12.0% 12.8% 6.7% <0.001
- Major 4.0% 4.2% 1.3% <0.001
- Minor 11.8% 12.3% 6.3% <0.001
Transfusions, non-CABG 6.1% 8.1% 3.7% 0.04
*P value for bivalirudin alone vs. heparin + IIb/IIIa inhibitor
Study Limitations
Even though the baseline characteristics of the 3 groups were well matched, the ACUITY PCI Gender sub-study is not a randomized trial
The ACUITY PCI Gender sub-study was under-powered for non-inferiority testing and subgroups All analyses should be considered hypothesis generating
Given the complexity of the trial, the study design was open label, and as such bias cannot be excluded
Conclusions and Clinical Implications In patients with moderate and high risk
ACS undergoing PCI Women undergoing PCI have similar long-
term ischemia outcomes as men but with significantly increased major bleeding at 30 days.
Among women, treatment with bivalirudin alone resulted in significantly reduced 30 day major bleeding and similar rates of 1-year composite ischemia and mortality compared to heparin + GP IIb/IIIa inhibitors.