1. Clinical Trial Results. org Characteristics, Management, and Outcomes of 5,557 Patients Age ≥90 Years With Acute Coronary Syndromes: Results From the CRUSADE Initiative Adam H. Skolnick, MD, Karen P. Alexander, MD, Anita Y. Chen, MS, Matthew T. Roe, MD, MSH, Charles V. Pollack, Jr, MD, MA, E. Magnus Ohman, MD, John S. Rumsfeld, MD, PhD, W. Brian Gibler, MD, Eric D. Peterson, MD, MPH, David J. Cohen, MD, MSc J Am Coll Cardiol 2007; 49:1790-7 The CRUSADE National Quality Improvement Initiative

2. Clinical Trial Results. org CRUSADE: Background Patients aged 90 and older (the “oldest old”) are often excluded from clinical trials and included in low numbers in clinical registriesPatients aged 90 and older (the “oldest old”) are often excluded from clinical trials and included in low numbers in clinical registries In particular, little is known about contemporary treatment and outcomes of acute coronary syndromes in such patientsIn particular, little is known about contemporary treatment and outcomes of acute coronary syndromes in such patients Patients aged 90 and older (the “oldest old”) are often excluded from clinical trials and included in low numbers in clinical registriesPatients aged 90 and older (the “oldest old”) are often excluded from clinical trials and included in low numbers in clinical registries In particular, little is known about contemporary treatment and outcomes of acute coronary syndromes in such patientsIn particular, little is known about contemporary treatment and outcomes of acute coronary syndromes in such patients Skolnick et al., JACC Vol.49, No.17, 2007

3. Clinical Trial Results. org CRUSADE: Objectives Describe key differences in baseline characteristics and ACS presentation among patients age 90 and older compared with a relatively younger cohortDescribe key differences in baseline characteristics and ACS presentation among patients age 90 and older compared with a relatively younger cohort Determine current treatment patterns in the oldest oldDetermine current treatment patterns in the oldest old Determine presenting characteristics associated with in-hospital mortality among the oldest old with ACSDetermine presenting characteristics associated with in-hospital mortality among the oldest old with ACS Describe key differences in baseline characteristics and ACS presentation among patients age 90 and older compared with a relatively younger cohortDescribe key differences in baseline characteristics and ACS presentation among patients age 90 and older compared with a relatively younger cohort Determine current treatment patterns in the oldest oldDetermine current treatment patterns in the oldest old Determine presenting characteristics associated with in-hospital mortality among the oldest old with ACSDetermine presenting characteristics associated with in-hospital mortality among the oldest old with ACS Skolnick et al., JACC Vol.49, No.17, 2007

4. Clinical Trial Results. org CRUSADE: Study Design  Primary Endpoint: Compare baseline characteristics, treatment patterns, and in-hospital outcomes of both cohorts Cohort A Pts >90 yrs n=5,557 Cohort A Pts >90 yrs n=5,557 Cohort B Pts 75 to 89 yrs n=46,270 Cohort B Pts 75 to 89 yrs n=46,270 51,827 patients >75 years with NSTE-ACS from CRUSADE Registry arriving at a participating facility either via the emergency department or by transfer within 24 h of onset of symptoms. In addition, initial evaluation must reveal 1 or more high-risk features including ST-segment depression, transient ST-segment elevation, or elevated levels of biomarkers 51,827 patients >75 years with NSTE-ACS from CRUSADE Registry arriving at a participating facility either via the emergency department or by transfer within 24 h of onset of symptoms. In addition, initial evaluation must reveal 1 or more high-risk features including ST-segment depression, transient ST-segment elevation, or elevated levels of biomarkers Skolnick et al., JACC Vol.49, No.17, 2007

5. Clinical Trial Results. org CRUSADE: Baseline Characteristics Characteristic 75-89 y.o. (N= 46,270) Age ≥ 90 (N=5,557)p-value Age (yrs) 81.0 ± 4.0 92.6 ± 2.6 <0.001 Caucasian (%) 85.786.1NS Female (%) 50.167.4<0.001 Diabetes Mellitus (%) 34.220.4<0.001 Hypertension (%) 76.173.7<0.001 Peripheral Vascular Disease (%) Peripheral Vascular Disease (%)15.610.7<0.001 Obesity (BMI>30) (%) 18.97.6<0.001 Recent/current smoker (%) 8.82.5<0.001 Family History of CAD (%) 25.014.8<0.001 Prior Aspirin use (%) 49.246.70.001 Previous PCI (%) 20.18.7<0.001 History of CHF (%) 26.939.3<0.001 Creatinine Clearance (ml/min) 36.023.9<0.001 Skolnick et al., JACC Vol.49, No.17, 2007

6. Clinical Trial Results. org CRUSADE: Findings at Admission Finding 75-89 yrs (N= 46,270) Age ≥ 90 (N=5,557)p-value ST-segment depressions (%) 36.935<0.001 CK-MB positive (%) 71.174.1<0.001 Troponin positive (%) 81.886.8<0.001 SBP <90 mm Hg (%) 4.14.90.004 HR >100 bpm (%) 25.528.9<0.001 Signs of CHF (%) 33.745.4<0.001 Skolnick et al., JACC Vol.49, No.17, 2007

7. Clinical Trial Results. org CRUSADE: In-Hospital Therapies Therapy 75-89 y.o. (N= 46,270) Age ≥ 90 (N=5,557)p-value Aspirin (%) 91.790.60.011 Beta-blocker (%) 82.280.70.017 Heparin, any route (%) 82.475.1<0.001 Clopidogrel (%) 40.135.5<0.001 Statin (%) 45.730.4<0.001 ACE-I (%) 47.145.30.025 Gp IIb/IIIa inhibitor (%) 29.212.0<0.001 Coronary Revasc, any (%) 40.112.6<0.001 PCI w/in 1 st 48 hours (%) 20.26.5<0.001 CABG (%) 9.41.1<0.001 Skolnick et al., JACC Vol.49, No.17, 2007

8. Clinical Trial Results. org CRUSADE: In-hospital Adverse Outcomes Outcome 75-89 y.o. (N=46,270) Age ≥ 90 (N=5,557)p-value Death (%) 7.812.0<0.001 MI (%) 3.53.0NS Stroke (%) 1.20.90.032 Cardiogenic Shock (%) 3.53.1NS CHF (%) 12.916.4<0.001 RBC Transfusion ŧ 14.112.8- Major Bleeding Event** ŧ (%) 13.19.9<0.001 Any Adverse Outcome Ł(%) 21.326.8- Skolnick et al., JACC Vol.49, No.17, 2007 ** Major Bleeding: (1) Hct decline >11% (2) Intracranial Hemorrhage (3) Retroperitoneal hemorrhage (4) Baseline Hct >27% w/ transfusion (5) Witnessed bleeding event w/ baseline Hct <28 w/ transfusion ŧ Excluded patients who underwent bypass surgery Ł Any adverse outcome: post-admission MI, cardiogenic shock, heart failure, stroke, or death

9. Clinical Trial Results. org CRUSADE: In-hospital Mortality Across Each Age Group With Increasing Adherence to Recommended Therapies In-Hospital Mortality (%) Guidelines recommended therapies included acute (<24h) aspirin, acute B-blockers, acute heparin and cardiac catheterization within 48h, and receipt of glycoprotein IIb/IIIa inhibitors for patients undergoing early catheterization. Skolnick et al., JACC Vol.49, No.17, 2007 Percent Adherence Score P-value for trend <0.001 P-value for age-treatment interaction = NS

10. Clinical Trial Results. org CRUSADE: Number of Therapies Provided and the Incidence of In-Hospital Bleeding Major Bleeding (%) *Therapies: (1) Aspirin (2) Beta-blocker (3) Heparin (4) Cath w/in 48 hrs w/ IIb/IIIa (5) Cath w/in 48 hrs. (CABG Pts and contraindications excluded) Skolnick et al., JACC Vol.49, No.17, 2007 Number of Therapies Received * P-value for trend <0.001 P-value for age-treatment interaction = NS

11. Clinical Trial Results. org CRUSADE: Multivariate Analysis: Independent Predictors of In-hospital Mortality Among Patients Aged ≥90 Finding Adjusted O.R. (95% C.I.) p-value Systolic BP (by 10 mm Hg) 1.19 (1.16-1.23) <0.001 Signs of CHF 1.76 (1.45-2.15) <0.001 Renal Insufficiency 1.48 (1.23-1.78) <0.001 Troponin Ratio 1.01 (1.00-1.02) <0.001 Diabetes Mellitus 1.38 (1.14-1.67) <0.001 BMI >25 vs. normal 1.30 (1.08-1.57) 0.026 Prior PCI 0.63 (0.45-0.90) 0.001 Dyslipidemia 0.78 (0.65-0.95) 0.014 Skolnick et al., JACC Vol.49, No.17, 2007

12. Clinical Trial Results. org CRUSADE: Limitations Further studies are necessary to validate this risk model and to better understand long-term outcomes in this challenging population Skolnick et al., JACC Vol.49, No.17, 2007

13. Clinical Trial Results. org CRUSADE: Summary Among the oldest old with ACS, traditional risk factors for CAD were less common compared with the patients aged 75-89, while CHF and renal dysfunction were more common. Among the oldest old with ACS, traditional risk factors for CAD were less common compared with the patients aged 75-89, while CHF and renal dysfunction were more common. After excluding those with contraindications, use of evidence-based medications, early catheterization and revascularization were less common among the oldest old After excluding those with contraindications, use of evidence-based medications, early catheterization and revascularization were less common among the oldest old Skolnick et al., JACC Vol.49, No.17, 2007

14. Clinical Trial Results. org CRUSADE: Summary Despite an association with major bleeding, increasing use of evidence-based therapies was associated with lower in-hospital mortality even among the oldest old with ACS Despite an association with major bleeding, increasing use of evidence-based therapies was associated with lower in-hospital mortality even among the oldest old with ACS Among the oldest old with ACS, diabetes and renal insufficiency were independently associated with increased in-hospital mortality, while elevated systolic BP, prior PCI and dyslipidemia were associated with decreased in- hospital mortality Among the oldest old with ACS, diabetes and renal insufficiency were independently associated with increased in-hospital mortality, while elevated systolic BP, prior PCI and dyslipidemia were associated with decreased in- hospital mortality Skolnick et al., JACC Vol.49, No.17, 2007

15. Clinical Trial Results. org CRUSADE: Summary ACS in the oldest old is associated with substantial morbidity and mortality compared with a younger elderly population Since adherence to ACC/AHA recommended therapies appears to be associated with improved outcomes in this group, advanced age alone should not deter efforts to optimize care for such patients ACS in the oldest old is associated with substantial morbidity and mortality compared with a younger elderly population Since adherence to ACC/AHA recommended therapies appears to be associated with improved outcomes in this group, advanced age alone should not deter efforts to optimize care for such patients Skolnick et al., JACC Vol.49, No.17, 2007