NT-proBNP measured early after high-risk MI associated with further CV outcomes
Prognostic Importance of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) Following High-Risk Myocardial Infarction in the PARADISE-MI Trial
Literature - Jering KS, Claggett BL, Pfeffer MA, et al. - Circ Heart Fail. 2023 May;16(5):e010259. doi: 10.1161/CIRCHEARTFAILURE.122.010259.Background
Patients who have experienced an acute myocardial infarction (MI) have an increased risk of further MI, stroke, HF and death, especially sudden death [1-5]. However, only a subset of patients, even after high-risk MI, experience these events, indicating a need for risk stratification in post-MI surveillance and treatment [4-9]. NT-proBNP is used as a prognostic marker of death and HF across multiple populations [10-11]. It remains unclear what the relationship is between NT-proBNP and recurrent MI and stroke in patients with ACS.
Aim of the study
The investigators examined the relationship between NT-proBNP and CV outcomes in patients following high-risk acute MI from the PARADISE-MI trial.
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Methods
PARADISE-MI (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) was a multicenter, double-blind, active comparator, randomized trial that compared the efficacy and safety of sacubitril/valsartan (97 mg sacubitril/93 mg valsartan twice daily) with ramipril (5 mg twice daily) in adult patients with a spontaneous acute MI complicated with LVEF ≤40% and/or pulmonary congestion, and ≥1 of 8 risk-augmenting factors. Patients with prior history of HF were excluded. In this prespecified subanalysis, a total of 1129 patients were included. Blood samples for NT-proBNP and hs-cTnT measurements were obtained within the first week of an MI. Data were analyzed with NT-proBNP as continuous variable or according to NT-proBNP quartiles (quartile 1: ≤896 ng/L; quartile 2: ≤897-1757 ng/L; quartile 3: 1758-3462 ng/L; quartile 4: >3462 ng/L). The median follow-up period was 29 months.
Outcomes
The primary outcome was a composite of CV mortality or incident HF (hospitalization or outpatient episode of symptomatic HF), analyzed as time-to-first event. Key secondary outcomes were CV mortality; HF hospitalization; all-cause mortality; and the composite of CV mortality, nonfatal MI or stroke.
Main results
NT-proBNP and clinical outcomes
- During follow-up, the primary composite outcome occurred in 147 patients (13.0%).
- The adjusted incidence rate of the primary composite outcome increased across NT-proBNP quartiles (2.0 per 100py; 3.7 per 100py; 6.8 per 100py; and 10.8 per 100py; for quartile 1, 2, 3, and 4, respectively).
- There was an association of log-transformed NT-proBNP with the primary composite outcome (adjusted HR: 1.44 per doubling of NT-proBNP; 95%CI: 1.22-1.69), which was independent of log-transformed hs-cTnT and other clinical characteristics. Similar results were obtained for key secondary outcomes.
- NT-proBNP did not modify the effects of sacubitril/valsartan vs. ramipril on the primary composite outcome (P for interaction=0.46).
- A total of 79 patients (7.0%) died. The incidence rate of all-cause mortality increased across NT-proBNP quartiles. This was mainly driven by the higher proportion of patients with CV-mortality across higher NT-proBNP quartiles.
Modeling risk for all-cause mortality
- Model discrimination for all-cause mortality with only log-transformed NT-proBNP did not differ from other risk stratification models such as GRACE 2.0 score (P=0.43) and TRA 2°P-TIMI score (P=0.67).
- The addition of log-transformed NT-proBNP to TRA 2°P-TIMI score improved model predication for all-cause mortality (C statistic: 0.74; 95%CI: 0.69-0.80 vs. C statistic: 0.67; 95%CI: 0.61-0.73; with and without NT-proBNP, respectively; P=0.007).
- The addition of log-transformed NT-proBNP did not improve the discrimination performance of GRACE 2.0 score (C statistic: 0.71; 95%CI: 0.65-0.77 vs. C statistic: 0.66; 95%CI: 0.59-0.73; with and without NT-proBNP, respectively; P=0.12).
Conclusion
In a prespecified analysis using data of the PARADISE-MI trial, NT-proBNP measured within the first week of a high-risk MI was associated with the primary composite outcome of CV mortality or incident HF, independent of hs-cTnT. Moreover, model discrimination for all-cause mortality with only early NT-proBNP measurements performed similar to well-validated risk scores such as GRACE 2.0 or TRA 2°P-TIMI in this high-risk post-MI patient population. The authors state that “our findings seem to support the recommendation for NT-proBNP measurement following MI to assist in risk stratification”.
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