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Jering KS, et al. Circ Heart Fail. 2023;doi:10.1161/CIRCHEARTFAILURE.122.010259.

Jering KS, et al. Circ Heart Fail. 2023;doi:10.1161/CIRCHEARTFAILURE.122.010259.

N-terminal pro-B-type natriuretic peptide level soon after acute MI may be prognostic of CV death or incident HF, independent of high-sensitivity troponin T, researchers reported.

This prespecified post hoc analysis of the PARADISE-MI trial was published in Circulation: Heart Failure.

"MI remains one of the leading causes of morbidity and mortality in the world, accounting for >15 million deaths per year. Following an acute MI, patients are at heightened risk of further MI, stroke, development of HF and death, especially sudden death. Yet even after high-risk MI, only a minority of patients experiences these events emphasizing the potential value of risk stratification to guide post-MI surveillance and treatment," Karola S. Jering, MD , cardiologist at the Carl J. and Ruth Shapiro Cardiovascular Center at Brigham and Women's Hospital, Heart and Vascular Center, and colleagues wrote. "Therefore, we have investigated the relationship between NT-proBNP and a range of cardiovascular outcomes in a prespecified biomarker substudy of the PARADISE-MI trial."

PARADISE-MI was a randomized, double-blind, parallel trial that evaluated the superiority of sacubitril/valsartan (Entresto, Novartis) compared with ramipril for the prevention of HF events in 5,669 patients with acute MI.

As Healio | Cardiology Today previously reported, sacubitril/valsartan did not significantly lower the rate of CV death or incident HF after acute MI compared with ramipril.

For this prespecified substudy of PARADISE-MI, researchers evaluated NT-proBNP and high-sensitivity troponin T that were collected at randomization in a subgroup of 1,129 patients.

The primary endpoint was a composite of CV death or incident HF — defined as hospitalization or outpatient HF requiring treatment — analyzed as time to first event. Additional endpoints included all-cause death and the composite of fatal or nonfatal MI or stroke.

Participants were stratified in quartiles of NT-proBNP: first quartile, 896 ng/L or less; second quartile, 897 ng/L to 1,757 ng/L; third quartile, 1,758 ng/L to 3,462 ng/L; and fourth quartile, greater than 3,462 ng/L.

Median NT-proBNP was 1,757 ng/L at trial randomization and participants were followed up during a median 29 months.

Researchers observed that patients in the fourth quartile of NT-proBNP were older, more often women and had more hypertension, atrial fibrillation, renal dysfunction and pulmonary congestion on presentation (P for all < .001), according to the study.

After adjusting for clinical variables and baseline high-sensitivity troponin T, Jering and colleagues reported that for every doubling of NT-proBNP, they observed an approximately 45% increased risk for the primary composite endpoint (adjusted HR = 1.45; 95% CI, 1.23-1.7).

NT-proBNP was also independently associated with all-cause death (aHR = 1.74; 95% CI, 1.38-2.21) and fatal or nonfatal MI or stroke (aHR = 1.24; 95% CI, 1.05-1.45), according to the study.

Moreover, NT-proBNP did not significantly modify the neutral treatment effect of sacubitril/valsartan relative to ramipril (P for interaction = .46), researchers reported.

"Elevations in NT-proBNP measured early after acute MI were associated with risk of subsequent nonfatal and fatal cardiovascular events, independent of clinical characteristics and high-sensitivity troponin T," the researchers wrote. "How risk stratification based on NT-proBNP can guide management strategies requires further study. The relative treatment effect of sacubitril/valsartan compared with ramipril in PARADISE-MI was not significantly modified by concentrations of NT-proBNP at randomization although this substudy was not powered to detect differential treatment effects according to NT-proBNP concentrations."