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

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

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 June 2000 Followed until Dec 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

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

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

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

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

Results Correlation with other risk factors BNPNT-proBNP Age eGFR LVEF Omland T, et al. JACC 2007;50:205-14

Results Risk of CV end-points BNPNT-proBNP OutcomeHR (95% CI)*p p Cardiovascular mortality 1.28 ( ) ( )<0.001 Fatal/nonfatal MI0.95 ( ) ( )0.43 Fatal/nonfatal CHF1.92 ( )< ( )<0.001 Fatal/nonfatal stroke1.35 ( ) ( )<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

Results Adjusted risk estimates BNPNT-proBNP OutcomeHR (95% CI)*p p Cardiovascular mortality 1.06 ( ) ( )<0.001 Fatal/nonfatal MI0.91 ( ) ( )0.84 Fatal/nonfatal CHF 1.62 ( )< ( )<0.001 Fatal/nonfatal stroke 1.15 ( ) ( )<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

Results Prognostic accuracy OutcomeBNP C-statistic NT-ProBNP C-statistic p Cardiovascular mortality0.58 ( )0.68 ( )<0.001 Fatal and non-fatal MI0.53 ( )0.53 ( )0.84 Fatal and non-fatal CHF0.69 ( )0.74 ( )0.005 Fatal and non-fatal stroke0.61 ( )0.70 ( )<0.001 Omland T, et al. JACC 2007;50:205-14

Results Incremental prognostic value OutcomeC-statistic Covariates C-statistic Covariates & BNP C-statistic Covariates & NT-proBNP CV mortality0.74 ( )0.75 ( )0.77 ( )* CHF0.82 ( )0.84 ( )*0.85 ( )* Stroke0.78 ( ) 0.80 ( ) * : p<0.05 vs covariates alone Omland T, et al. JACC 2007;50:205-14

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

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

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