NT-proBNP in the Early Convalescent Phase after High-Risk Myocardial Infarction Is Associated with Adverse Cardiovascular Outcomes: the PARADISE-MI Trial

Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with heart failure (HF) hospitalizations and death when measured during a myocardial infarction (MI). However, NT-proBNP concentrations change following the initial ischemic insult and less is known about the prognostic importance of NT-proBNP in the early convalescent phase. Methods PARADISE-MI randomized 5661 patients with MI complicated by LVEF ≤40% and/or pulmonary congestion to sacubitril/valsartan or ramipril. Patients with available week 2 NT-proBNP concentrations and without-incident HF between randomization and week 2 (n = 1062) were analyzed. Associations of week 2 NT-proBNP with subsequent clinical outcomes were evaluated in landmark analyses using Cox models adjusted for clinical characteristics, including LVEF, baseline NT-proBNP and atrial fibrillation. Results Median 2-week NT-proBNP concentration was 1391 [676–2507] ng/L. Patients in the highest NT-proBNP quartile (≥2507 ng/L) were older, had lower left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR), higher Killip class, and more atrial fibrillation. Higher NT-proBNP concentrations were independently associated with greater risk of cardiovascular death or incident HF (adjusted hazard ratio [aHR], 1.65 per doubling of NT-proBNP; 95% confidence interval [CI], 1.31–2.09), HF hospitalization (aHR, 1.87; 95% CI, 1.38–2.54), recurrent myocardial infarction (aHR, 1.46; 95% CI, 1.09–1.95) and all-cause death (aHR, 1.85; 95% CI, 1.35–2.53). Conclusions Patients with elevated NT-proBNP concentrations approximately 2 weeks after a high-risk myocardial infarction are at heightened risk of incident HF, recurrent coronary events, and death independent of baseline NT-proBNP concentrations and clinical characteristics. Elevations in NT-proBNP concentrations in the early convalescent phase may assist in risk stratification and the identification of patients in need of more advanced preventive treatment approaches.