Prognostic Importance of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) Following High-Risk Myocardial Infarction in the PARADISE-MI Trial

Circ Heart Fail. 2023 May;16(5):e010259. doi: 10.1161/CIRCHEARTFAILURE.122.010259. Epub 2023 May 1.


Background: NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a potent predictor of death and heart failure (HF) across multiple populations. We evaluated the prognostic importance of NT-proBNP in patients with acute myocardial infarction (MI) complicated by left ventricular systolic dysfunction, pulmonary congestion, or both and ≥1 of 8 risk-augmenting factors enrolled in the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction).

Methods: Patients were randomized to sacubitril/valsartan 200 mg or ramipril 5 mg twice daily within 0.5 to 7 days of a MI. Patients with prior HF were excluded. NT-proBNP and hs-cTnT (high-sensitivity troponin T) were collected at randomization in a prespecified substudy of 1129 patients. The primary end point of PARADISE-MI was a composite of cardiovascular death or incident HF (hospitalization or outpatient symptomatic HF), analyzed as time-to-first event; additional end points included all-cause death and the composite of fatal or nonfatal MI or stroke.

Results: Median NT-proBNP was 1757 ng/L (25th-75th percentiles, 896-3462 ng/L) at randomization (4.0±1.8 days after the index MI). Patients in the highest quartile of NT-proBNP were older, more commonly women and had more hypertension, atrial fibrillation, renal dysfunction, and pulmonary congestion on presentation (all P<0.001). NT-proBNP was strongly associated with the primary end point (adjusted hazard ratio, 1.45 per doubling of NT-proBNP; [95% CI, 1.23-1.70]), adjusted for clinical variables and baseline hs-cTnT. NT-proBNP was also independently associated with all-cause death (adjusted hazard ratio, 1.74 [95% CI, 1.38-2.21]) and fatal or nonfatal MI or stroke (adjusted hazard ratio, 1.24 [95% CI, 1.05-1.45]). NT-proBNP did not significantly modify the neutral treatment effect of sacubitril/valsartan relative to ramipril (P interaction=0.46).

Conclusions: Within the first week of a high-risk MI NT-proBNP is associated with incident HF, death and atherosclerotic events. This prognostic information is independent of hs-cTnT.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT02924727.

Keywords: biomarkers; clinical trial; death; heart failure; myocardial infarction; natriuretic peptide, brain; troponin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Female
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Humans
  • Myocardial Infarction* / drug therapy
  • Natriuretic Peptide, Brain / therapeutic use
  • Peptide Fragments / therapeutic use
  • Prognosis
  • Prospective Studies
  • Ramipril / therapeutic use
  • Valsartan / therapeutic use


  • sacubitril
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Ramipril
  • Biomarkers
  • Valsartan
  • Peptide Fragments

Associated data