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