roxana mehran, on behalf of the acuity investigators
DESCRIPTION
Long-term Outcomes of Patients with ACS and Chronic Renal Insufficiency Undergoing PCI and being treated with Bivalirudin vs UFH/Enoxaparin plus a GP IIb/IIIa Inhibitor: Results from the Randomized ACUITY Trial. Roxana Mehran, on behalf of the ACUITY investigators. Disclosures. Medical - PowerPoint PPT PresentationTRANSCRIPT
Long-term Outcomes of Patients with ACS and Chronic Renal Insufficiency Undergoing
PCI and being treated with Bivalirudin vs UFH/Enoxaparin plus a GP IIb/IIIa Inhibitor: Results from the Randomized ACUITY Trial
Long-term Outcomes of Patients with ACS and Chronic Renal Insufficiency Undergoing
PCI and being treated with Bivalirudin vs UFH/Enoxaparin plus a GP IIb/IIIa Inhibitor: Results from the Randomized ACUITY Trial
Roxana Mehran, on behalf of the ACUITY investigators
Roxana Mehran, on behalf of the ACUITY investigators
DisclosuresDisclosures
Moderate-high risk
ACS
ACUITY Study DesignACUITY Study Design
An
gio
gra
ph
y w
ith
in 7
2h
Aspirin in allClopidogrel
dosing and timingper local practice
Aspirin in allClopidogrel
dosing and timingper local practice
UFH orEnoxaparin+ GP IIb/IIIa
Bivalirudin+ GP IIb/IIIa
BivalirudinAlone
R*
*Stratified by pre-angiography thienopyridine use or administration*Stratified by pre-angiography thienopyridine use or administration
Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819)
Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819)
ACUITY Design. Stone GW et al. AHJ 2004;148:764–75ACUITY Design. Stone GW et al. AHJ 2004;148:764–75
Medicalmanagement
PCI
CABG
UF Heparin Enoxaparin Bivalirudin
U/Kg mg/Kg mg/kg
Bolus 60 1.0 sc bid 0.1 iv
Infusion/h 121 0.25 iv
PCIACT
200-250s
0.30 iv bolus2
0.75 iv bolus3
0.50 bolus iv
1.75/h infusion iv4
Study MedicationsStudy Medications Anti-thrombin agents (started pre-angiography) 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 used
ACUITY Design. Stone GW et al. AHJ 2004;148:764–75ACUITY Design. Stone GW et al. AHJ 2004;148:764–75
Primary EndpointsPrimary Endpoints
Net Clinical Outcomes Death, MI, unplanned revascularization for ischemia or non-
CABG major bleeding
Composite Ischemia Death, MI or unplanned revascularization for ischemia
Major Bleeding (Non-CABG) 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
Net Clinical Outcomes Death, MI, unplanned revascularization for ischemia or non-
CABG major bleeding
Composite Ischemia Death, MI or unplanned revascularization for ischemia
Major Bleeding (Non-CABG) 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
ACUITY Design. Stone GW et al. AHJ 2004;148:764–75ACUITY Design. Stone GW et al. AHJ 2004;148:764–75
Background and Objectives of the Current Analysis
Background and Objectives of the Current Analysis
Background Patients with ACS and chronic renal
insufficiency have increased ischemic and bleeding complications after PCI
Objectives Evaluate the impact of renal insufficiency and
antithrombin strategy on the outcomes in patients presenting with ACS and undergoing PCI
Background Patients with ACS and chronic renal
insufficiency have increased ischemic and bleeding complications after PCI
Objectives Evaluate the impact of renal insufficiency and
antithrombin strategy on the outcomes in patients presenting with ACS and undergoing PCI
Management Strategy (N=13,819)Management Strategy (N=13,819)
56.4%
11.1%32.5%CABG (n=1,539)CABG (n=1,539) Medical Rx (n=4,491)Medical Rx (n=4,491)
PCI (n=7,789)PCI (n=7,789)
CrCl ≥60 mL/minN=5994
CrCl <60 mL/minN=1352
Baseline Characteristics by Renal Function in PCI Patients
Baseline Characteristics by Renal Function in PCI Patients
CrCL ≥ 60 mL/minN=5994
CrCL < 60 mL/minN=1352
P-value
Age (median [range]) 60 (21-90) 76 (37-95) <0.0001
≥75 years 8.8% 56.2% <0.0001
Female 22.4% 44.7% <0.0001
Diabetes 26.6% 30.8% 0.002
Current Smoker 34.7% 14.3% <0.0001
Prior MI 29.4% 32.8% 0.01
Prior PCI 37.8% 41.8% 0.007
Prior CABG 16.0% 23.5% <0.0001
Family History CAD 53.9% 44.4% <0.0001
Anemia 12.6% 29.6% <0.0001
Hypertension 62.6% 77.9% <0.0001
Hyperlipidemia 54.8% 59.8% 0.0008
CrCL ≥ 60 mL/minN=5994
CrCL < 60 mL/minN=1352
P-value
CKMB/Troponin or
ST-segment Deviation
76.2% 76.3% 0.95
CKMB/Troponin
Elevation65.5% 63.8% 0.27
ST-segment deviation
34.6% 41.6% <0.0001
Prior Thienopyridine exposure
67.2% 71.9% 0.0009
Baseline Characteristics by Renal Function in PCI Patients
Baseline Characteristics by Renal Function in PCI Patients
4.6%
11.6%
8.0%
12.7%
21.7%
12.2%
Net clinical outcome Composite ischemia Major bleeding (non-CABG)
CrCl ≥60 mL/min (n=5994)
CrCl <60 mL/min (n=1352)
30-Day Outcomes by Renal Function in PCI Patients
30-Day Outcomes by Renal Function in PCI Patients
P<0.0001
P<0.0001 P<0.0001
30 D
ay E
ven
ts (
%)
30 day Outcomes in Renally Impaired PCI Patients
30 day Outcomes in Renally Impaired PCI Patients
UFH/Enox + GP IIb/IIIa vs. Bivalirudin + GP IIb/IIIa vs. Bivalirudin AloneUFH/Enox + GP IIb/IIIa vs. Bivalirudin + GP IIb/IIIa vs. Bivalirudin Alone
11.6% 11.8%
20.8%
17.7%
26.3%
14.6%12.0%
17.9%
7.0%
Net clinical outcome Composite ischemia Major bleeding (non-CABG)
Hep/Enox + GP Iib/IIIa (N=457) Bivalirudin + GP Iib/IIIa (N=453) Bivalirudin alone (N=442)
P=0.27 P=0.85 P=0.02
30 D
ay E
ven
ts (
%)
30-Day Major Bleeding (non-CABG) – Renally Impaired PCI pts
30-Day Major Bleeding (non-CABG) – Renally Impaired PCI pts
UFH/Enox + IIb/IIIa(N=457)
Bivalirudin + IIb/IIIa
(N=453)
Bivalirudin
alone(N=442)
P value*
Major bleeding 11.8% 17.7% 7.0% 0.01
Intracranial 0% 0% 0% N/A
Retroperitoneal 1.3% 2.2% 0.2% 0.06
Access site 6.3% 7.5% 1.6% <0.001
- req interv/surgery 1.3% 1.5% 0.7% 0.34
- hematoma ≥5 cm 5.7% 6.0% 1.4% <0.001
Hgb ≥3 g/dL with overt source 5.3% 7.3% 2.5% 0.03
Hgb ≥4 g/dL with no overt source 1.1% 2.6% 1.1% 0.96
Blood transfusion 6.1% 11.0% 4.5% 0.29
Reoperation for bleed 0% 0.2% 0.2% 0.31
*P value for bivalirudin alone vs. heparin + IIb/IIIa inhibitor*P value for bivalirudin alone vs. heparin + IIb/IIIa inhibitor
17.2%
2.2%
7.2%
25.6%
Composite Ischemia Mortality
CrCl ≥60 mL/min (n=5994)
CrCl <60 mL/min (n=1352)
1-Year Outcomes by Renal Function in PCI Patients
1-Year Outcomes by Renal Function in PCI Patients
P<0.0001
P<0.0001
1 Y
ear
Eve
nts
(%
)
1-Year Outcomes in Renally Impaired PCI Patients by Treatment Group
1-Year Outcomes in Renally Impaired PCI Patients by Treatment Group
0.1 1 10
Hazard Ratio ±95% CI
Composite Ischemia 1.14 (0.87-1.49)
HR (95% CI)
Mortality 0.77 (0.45-1.33)
Bivalirudin Better UFH/Enox+ IIb/IIIa Better
Study Limitations Study Limitations
Subgroup analysis, results should be considered hypothesis generating
Treatment was open label and not randomized based upon renal function
Subgroup analysis, results should be considered hypothesis generating
Treatment was open label and not randomized based upon renal function
ConclusionsConclusions
In patients with ACS who undergo invasive management, the presence of renal insufficiency is associated with higher rates of composite ischemia and mortality at 1 year
Bivalirudin monotherapy improved early clinical outcomes compared to UFH/Enox + GP IIb/IIIa inhibitors by reducing 30-day major bleeding, and resulted in similar rates of one year composite ischemia and mortality
In patients with ACS who undergo invasive management, the presence of renal insufficiency is associated with higher rates of composite ischemia and mortality at 1 year
Bivalirudin monotherapy improved early clinical outcomes compared to UFH/Enox + GP IIb/IIIa inhibitors by reducing 30-day major bleeding, and resulted in similar rates of one year composite ischemia and mortality