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

Moderate- high risk ACS ACUITY Study Design Angiography within 72h Aspirin in all Clopidogrel dosing and timing per local practice Aspirin in all Clopidogrel dosing and timing per local practice UFH or Enoxaparin + GP IIb/IIIa Bivalirudin + GP IIb/IIIa Bivalirudin Alone R* *Stratified by pre-angiography thienopyridine use or administration Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819) ACUITY Design. Stone GW et al. AHJ 2004;148:764–75 Medical management PCI CABG

UF HeparinEnoxaparinBivalirudin U/Kgmg/Kgmg/kg Bolus601.0 sc bid0.1 iv Infusion/h iv PCI ACT s 0.30 iv bolus iv bolus bolus iv 1.75/h infusion iv 4 Study Medications  Anti-thrombin agents (started pre-angiography) 1 Target aPTT seconds 2 If last enoxaparin dose ≥8h - <16h before PCI; 3 If maintenance dose discontinued or ≥16h from last dose 4 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;148:764–75

Primary 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;148:764–75

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) 56.4% 11.1% 32.5% CABG (n=1,539) Medical Rx (n=4,491) PCI (n=7,789) CrCl ≥60 mL/min N=5994 CrCl <60 mL/min N=1352

Baseline Characteristics by Renal Function in PCI Patients CrCL ≥ 60 mL/min N=5994 CrCL < 60 mL/min N=1352 P-value Age (median [range])60 (21-90)76 (37-95)< ≥75 years8.8%56.2%< Female22.4%44.7%< Diabetes26.6%30.8%0.002 Current Smoker34.7%14.3%< Prior MI29.4%32.8%0.01 Prior PCI37.8%41.8%0.007 Prior CABG16.0%23.5%< Family History CAD53.9%44.4%< Anemia12.6%29.6%< Hypertension62.6%77.9%< Hyperlipidemia54.8%59.8%0.0008

CrCL ≥ 60 mL/min N=5994 CrCL < 60 mL/min N=1352 P-value CKMB/Troponin or ST-segment Deviation 76.2%76.3%0.95 CKMB/Troponin Elevation 65.5%63.8%0.27 ST-segment deviation 34.6%41.6%< Prior Thienopyridine exposure 67.2%71.9% Baseline Characteristics by Renal Function in PCI Patients

30-Day Outcomes by Renal Function in PCI Patients P< Day Events (%)

30 day Outcomes in Renally Impaired PCI Patients UFH/Enox + GP IIb/IIIa vs. Bivalirudin + GP IIb/IIIa vs. Bivalirudin Alone P=0.27P=0.85P= Day Events (%)

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 bleeding11.8%17.7%7.0% 0.01 Intracranial0% N/A Retroperitoneal1.3%2.2%0.2% 0.06 Access site6.3%7.5%1.6% < req interv/surgery1.3%1.5%0.7% hematoma ≥5 cm5.7%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 transfusion6.1%11.0%4.5% 0.29 Reoperation for bleed0%0.2% 0.31 *P value for bivalirudin alone vs. heparin + IIb/IIIa inhibitor

1-Year Outcomes by Renal Function in PCI Patients P< Year Events (%)

1-Year Outcomes in Renally Impaired PCI Patients by Treatment Group Hazard Ratio ±95% CI Composite Ischemia1.14 ( ) HR (95% CI) Mortality0.77 ( ) Bivalirudin BetterUFH/Enox+ IIb/IIIa Better

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

Conclusions  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