The CRUSADE Bleeding Score

1. The CRUSADE Bleeding Score A validated risk prediction tool for estimation of baseline risk of in-hospital major bleeding in patients with NSTEMI Sumeet Subherwal, Richard G. Bach, Anita Y. Chen, Brian F. Gage, Sunil V. Rao, Tracy Y. Wang, W. Brian Gibler, E. Magnus Ohman, Matthew T. Roe, Eric D. Peterson, Karen P. Alexander Duke Clinical Research Institute and Washington University St. Louis

2. Background • Validated risk stratification tools exist for baseline ischemic risk (TIMI, PURSUIT, GRACE ACS), however estimation of baseline bleeding risk in patients with NSTEMI is difficult because existing tools: • include treatment variables (i.e. antithrombotics or invasive procedures) • derived from highly selected patient populations

3. CRUSADE Major Bleeding Model • CRUSADE Quality Improvement Initiative • February 15, 2003 to December 31, 2006 • n=89,134 NSTEMI patients at 485 US hospitals • Excluded unstable angina, home warfarin, transfer out, deaths within 48 hours • In-hospital Major Bleeding (Censored at CABG) • Absolute HCT drop ≥12% (Baseline – Nadir) • Intracranial hemorrhage or retroperitoneal bleed • Transfusion if baseline HCT ≥28% • Transfusion if baseline HCT <28% AND witnessed bleed • Divided into derivation (80% of N) and validation cohorts (20% of N) • Incorporated clinically and statistically significant univariate associations into a multivariable model using generalized estimating equations (GEE)

4. Baseline Characteristics *Median (25th, 75th percentile) †Prior vascular disease defined as h/o stroke or peripheral arterial disease ‡ Creatinine clearance as estimated by Cockcroft-Gault Formula

5. Multivariable Predictors of Bleeding Prior vascular disease defined as h/o stroke or peripheral arterial disease Note: Heart rate is truncated @ <70 bpm; CrCl: Cockcroft-Gault is truncated @ >90 mL/min

6. CRUSADE Bleeding Score • The CRUSADE Bleeding Score was developed by assigning a weighted integer to each independent predictor based on the predictor’s coefficient in the reduced regression model • The CRUSADE Bleeding Score (range 1-100 points) equals the sum of weighted integers for independent predictors

7. CRUSADE Bleeding Score Nomogram Note: Heart rate is truncated @ <70 bpm; CrCl: Cockcroft-Gault is truncated @ >90 mL/min; Prior Vascular disease is defined as prior PAD or stroke

8. CRUSADE Bleeding Score

9. CRUSADE Bleeding Score Risk Quintiles Patients were categorized into risk quintiles based on CRUSADE Bleeding Score

10. Major Bleeding by Risk Quintiles in Derivation and Validation Cohorts

11. Major Bleeding by Antithrombotic therapy • ≥2 Antithrombotics (anti-platelet [aspirin or clopidogrel], anti-coagulant, or GP IIb/IIIa; n=50,969; c-index 0.72) • <2 Antithrombotics (anti-platelet, anti-coagulant, or GP IIb/IIIa; n=5,931; c-index 0.73)

12. Major Bleeding by Invasive or Conservative Approach • Conservative Approach (≥2 antithrombotics and no catheterization; n=3,200; c-index 0.68) • Invasive Approach (≥2 antithrombotics and no catheterization; n=43,492; c-index 0.73)

13. Mortality in those who did or did not have a Major Bleed across Risk Quintiles

14. Conclusion • The CRUSADE Bleeding Score combines 8 predictors of major bleeding into a simple validated prediction tool that estimates baseline risk of in-hospital major bleeding in patients with NSTEMI • Preserved discrimination across treatment subgroups • Complements ischemic risk prediction tools to better enable clinicians to consider the potential adverse outcomes in patients with NSTEMI prior to initiation of therapy