Alexandra J. Lansky on behalf of the ACUITY Investigators

1. 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

2. Disclosures • Alexandra J. Lansky • Insert disclosures here

3. Medical management UFH/Enox + GP IIb/IIIa (n=4,603) PCI Bivalirudin + GP IIb/IIIa (n=4,604) Angiography within 72h R* Bivalirudin Alone (n=4,612) CABG Study Design – First Randomization Moderate and high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819) Moderate and high risk ACS (n=13,819) Aspirin in all Clopidogrel dosing and timing per local practice *Stratified by pre-angiography thienopyridine use or administration

4. UFH/Enox + GP IIb/IIIa (N=4,603) GPI upstream (N=2294) GPI CCL for PCI (N=2309) Bivalirudin + GP IIb/IIIa (N=4,604) GPI upstream (N=2311) R* GPI CCL for PCI (N=2293) Bivalirudin Alone (N=4,612) Study Design – Second Randomization Moderate and high risk unstable angina or NSTEMI undergoing an invasive strategy Moderate and high risk ACS (n=13,819) Aspirin in all Clopidogrel dosing and timing per local practice *Stratified by pre-angiography thienopyridine use or administration

5. Heparin + IIb/IIIa N = 2,561 Bivalirudin + IIb/IIIa N = 2,609 Bivalirudin alone N = 2,619 Management Strategy (N=13,819) Medical Rx (n=4,491) CABG (n=1,539) 32.2% 11.4% 56.4% PCI (n=7,789)

6. Study Medications • Anti-thrombin agents (started pre angiography) 1 Target aPTT 50-75 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 5 Bivalirudin option for off-pump same as PCI dose. For on-pump bivalirudin discontinued 2 hours before 6 Option to continue with pre-PCI anti-thrombotic regimen at physician discretion

7. 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

8. 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

9. 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

10. Baseline Characteristics by Gender Males vs. Females *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).

11. Clinical Outcomes by Gender Males vs. Females

12. Baseline Characteristics – Female PCI pts *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).

13. Baseline High Risk Features – Female PCI pts

14. Antiplatelet Medications – Female PCI pts

15. Procedural Characteristics – Female PCI pts

16. Device Use – Female PCI pts

17. p=0.18 UFH/Enox + GP IIb/IIIa Bivalirudin + GP IIb/IIIa Bivalirudin alone 1-Year Composite Ischemia – Female PCI pts Heparin* + IIb/IIIa vs. Bivalirudin + IIb/IIIa vs. Bivalirudin Alone 25 20 15 Mortality (%) 10 5 0 0 30 60 90 120 150 180 210 240 270 300 330 360 395 Days from Randomization *Heparin=unfractionated or enoxaparin

18. p=0.23 UFH/Enox + GP IIb/IIIa Bivalirudin + GP IIb/IIIa Bivalirudin alone 1-Year Mortality – Female PCI pts Heparin* + IIb/IIIa vs. Bivalirudin + IIb/IIIa vs. Bivalirudin Alone 5 4 3 Mortality (%) 2 1 0 0 30 60 90 120 150 180 210 240 270 300 330 360 395 Days from Randomization *Heparin=unfractionated or enoxaparin

19. 30-Day Major Bleeding (non-CABG) – Female PCI pts *P value for bivalirudin alone vs. heparin + IIb/IIIa inhibitor

20. Bleeding Endpoints – Female PCI pts *P value for bivalirudin alone vs. heparin + IIb/IIIa inhibitor

21. 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

22. 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.