NT-proBNP measured early after high-risk MI associated with further CV outcomes

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

References

Find this article online at Circ Heart Fail.