Identification of potential outcome benefit from ACE inhibition after acute coronary syndrome: a biomarker approach using N-terminal proBNP

Objective To consider whether patients most likely to benefit from ACE inhibition in routine practice after acute coronary syndrome (ACS) may be identified from plasma natriuretic peptide concentrations. Design Observational cohort study. Setting Teaching hospital coronary care unit. Patients 1725 patients admitted with acute coronary syndrome (56.3% ST elevation ACS; median age 67, range 24-97 years). Measurements Using Cox proportional hazards analysis, we assessed the adjusted predictive value for major adverse cardiac events (MACE) of prescription of an ACE inhibitor, of plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) and for interaction between these factors. To adjust for demographic differences between patients prescribed or not prescribed an ACE inhibitor, a factor correcting for likelihood of ACE inhibitor prescription (propensity score) was included in the analysis. Outcome measures The primary end point was the occurrence of MACE (death, recurrent myocardial infarction or hospitalisation with heart failure). Results During the index admission ACE inhibitor was prescribed for 1267/1725 (73.4%) patients. During follow-up (median 528 days, range 0-3873 days), 534/1725 patients experienced MACE. After covariable adjustment, NT-proBNP showed linear association with risk of MACE (p<0.005), strongest for patients with NT-proBNP in the top quartile of observed values (HR=2.768, p<0.001). Only for patients with NT-proBNP in the top quartile was prescription of ACE inhibitor associated with reduction in risk of MACE (HR=0.532, p=0.003). This association was maintained after correction for propensity scores (HR=0.599, p=0.003). Conclusions Prognostic benefit from ACE inhibition was seen only in patients with the most marked elevation of plasma NT-proBNP. Plasma NT-proBNP may be a useful indicator of the appropriateness of individual prescription of ACE inhibitor treatment across the spectrum of ACS.