1. Prognostic Value of B-Type Natriuretic Peptides in Patients with Stable Coronary Artery Disease The PEACE trial Omland T, et al. JACC 2007;50:205-14

2. Objectives In low-risk patients with stable coronary disease and preserved LV function, to assess: — the association between BNP and NT-proBNP and the incidence of specific cardiovascular events — the incremental prognostic information obtained from these two biomarkers compared with traditional risk factors — the ability of BNP and NT-proBNP to identify patients who may benefit from ACE inhibition Omland T, et al. JACC 2007;50:205-14

3. A double-blind, placebo-controlled, randomized trial Sponsored by the National Heart, Lung, and Blood Institute Study medication and additional support provided by Abbott Laboratories / Knoll Natriuretic peptide analyses supported by Abbott Laboratories and Roche Diagnostics N = 8290 Inclusion Nov 1996 - June 2000 Followed until Dec 31 2003 Median follow-up time = 4.8 years The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial Omland T, et al. JACC 2007;50:205-14

4. Inclusion Criteria Age  50 years Coronary artery disease — MI, or — CABG or PCI, or — Coronary angiogram with obstruction of  50% luminal diameter in at least one native vessel LVEF > 40% Tolerated 2 week run-in of 2 mg/day trandolapril Omland T, et al. JACC 2007;50:205-14

5. Major Exclusions Current use, indication for or contraindication to ACE-I or ARB CV event in previous 3 months Planned elective coronary revasc Creatinine > 2.0 mg/dl Potassium > 5.5 mEq/L Limited 5-year survival Omland T, et al. JACC 2007;50:205-14

6. Biomarker substudy N=3762 No major difference between patients included vs those not included Blood samples centrifuged within 45 min EDTA plasma stored at -70°C or lower until 2005 Baseline plasma samples analyzed for BNP and NT-proBNP on the same day BNP: 2-step microparticle enzyme immunoassay on an Abbott Ax Sym analyzer NT-proBNP: electrochemiluminescence immunoassay on a Modular platform (Roche) Omland T, et al. JACC 2007;50:205-14

7. Results Patient characteristics VariableN (%) or Mean ±SD Age (yrs) 63.7  8.2 Female sex713 (19.0) Race Caucasian3448 (91.7) Previous MI2112 (56.2) Diabetes616 (16.4) Hypertension1682 (44.7) LVEF 58.7  9.6 Omland T, et al. JACC 2007;50:205-14

8. Results Correlation with other risk factors BNPNT-proBNP Age0.270.39 eGFR-0.14-0.22 LVEF-0.09-0.18 Omland T, et al. JACC 2007;50:205-14

9. Results Risk of CV end-points BNPNT-proBNP OutcomeHR (95% CI)*p p Cardiovascular mortality 1.28 (1.08-1.51)0.0042.00 (1.69-2.36)<0.001 Fatal/nonfatal MI0.95 (0.83-1.08)0.431.05 (0.93-1.18)0.43 Fatal/nonfatal CHF1.92 (1.61-2.27)<0.0012.81 (2.33-3.38)<0.001 Fatal/nonfatal stroke1.35 (1.10-1.65)0.0031.93 (1.58-2.36)<0.001 Adjusted for randomization status Hazard Ratio and 95%CI per 1 SD pg/ml in log BNP and log NT-proBNP Omland T, et al. JACC 2007;50:205-14

10. Results Adjusted risk estimates BNPNT-proBNP OutcomeHR (95% CI)*p p Cardiovascular mortality 1.06 (0.87-1.28)0.571.69 (1.38-2.07)<0.001 Fatal/nonfatal MI0.91 (0.77-1.07)0.241.02 (0.87-1.19)0.84 Fatal/nonfatal CHF 1.62 (1.32-1.97)<0.0012.35 (1.86-2.98)<0.001 Fatal/nonfatal stroke 1.15 (0.91-1.45)0.241.63 (1.26-2.12)<0.001 Adjusted for randomization status, age, sex, BMI, LVEF < 50%, eGFR, current smoking, history of hypertension or measured hypertension, history of MI, diabetes, stroke, PCI, CABG, total chol, CRP, use of a beta blocker, lipid- lowering drug, aspirin or antiplatelet medication, and of a diuretic. Hazard Ratio and 95%CI per 1 SD pg/ml in log BNP and log NT-proBNP Omland T, et al. JACC 2007; 50:205-14

11. Results Prognostic accuracy OutcomeBNP C-statistic NT-ProBNP C-statistic p Cardiovascular mortality0.58 (0.53-0.63)0.68 (0.63-0.73)<0.001 Fatal and non-fatal MI0.53 (0.49-0.57)0.53 (0.49-0.56)0.84 Fatal and non-fatal CHF0.69 (0.64-0.73)0.74 (0.69-0.79)0.005 Fatal and non-fatal stroke0.61 (0.55-0.67)0.70 (0.65-0.75)<0.001 Omland T, et al. JACC 2007;50:205-14

12. Results Incremental prognostic value OutcomeC-statistic Covariates C-statistic Covariates & BNP C-statistic Covariates & NT-proBNP CV mortality0.74 (0.70 -0.79)0.75 (0.71 - 0.80)0.77 (0.73 - 0.81)* CHF0.82 (0.78 - 0.86)0.84 (0.80 - 0.87)*0.85 (0.81 - 0.88)* Stroke0.78 (0.73 - 0.83) 0.80 (0.76 - 0.85 ) * : p<0.05 vs covariates alone Omland T, et al. JACC 2007;50:205-14

13. Conclusions In low-risk patients with stable coronary disease and preserved LV function: — Baseline NT-proBNP concentrations are independently related to the incidence of: — CV death — CHF — Stroke — Baseline BNP concentrations are independently related to the incidence of: — CHF — Neither peptide was predictive of MI Omland T, et al. JACC 2007;50:205-14

14. Conclusions Baseline NT-proBNP concentrations provide incremental prognostic information to traditional risk factors for: — CV death — CHF Baseline BNP concentrations provide incremental prognostic information to traditional risk factors for: — CHF Omland T, et al. JACC 2007;50:205-14

15. Conclusions Natriuretic peptide determination did not identify a subset of patients who experienced a greater degree of benefit from ACE- inhibition Omland T, et al. JACC 2007;50:205-14