Prognostic importance of NT-proBNP following high-risk myocardial infarction in the PARADISE-MI Trial

Abstract

Background/Introduction N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of ventricular wall stress and a potent predictor of death and heart failure (HF) across multiple populations (from healthy insurance applicants to various disease entities). Purpose To evaluate the prognostic importance of NT-proBNP in patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction, pulmonary congestion, or both and ≥1 of 8 predefined risk-augmenting factors (age ≥70 years, diabetes, previous MI, eGFR <60 ml/min/1.73 m2, atrial fibrillation, LVEF <30%, Killip class III/IV, or ST elevation MI without reperfusion) enrolled in PARADISE-MI. Methods Patients were randomized to sacubitril/valsartan 200mg or ramipril 5mg twice daily within 0.5 to 7 days of presenting with an AMI. Patients with prior HF were excluded. NT-proBNP and high-sensitivity troponin T (hsTnT) were collected at randomization in a prespecified sub-study of 1129 patients. The primary endpoint of PARADISE-MI was a time-to-first composite of cardiovascular (CV) death or incident HF (hospitalization or outpatient symptomatic HF); secondary endpoints included all-cause death and the composite of fatal or non-fatal MI or stroke. Results Median NT-proBNP was 1757 pg/ml [interquartile range, 896–3462 pg/ml] at randomization (4.0±1.8 days after presentation with the index MI). Patients with higher NT-proBNP levels at baseline were older, more commonly women and more frequently had hypertension, atrial fibrillation, renal dysfunction, and pulmonary congestion at randomization (all p<0.001). NT-proBNP concentrations were only weakly correlated with levels of hsTnT at randomization (r=0.38, p<0.001). NT-proBNP at baseline was strongly associated with the primary composite endpoint (adjusted HR 1.45 per doubling NT-proBNP; 95% CI, 1.23–1.70), independent of clinical variables as well as hsTnT (Figure). NT-proBNP was also independently associated with all-cause death (aHR 1.74; 95% CI, 1.38–2.21) and fatal or non-fatal MI or stroke (aHR 1.24; 95% CI, 1.05–1.45). The relative effect of sacubitril/valsartan versus ramipril on the primary composite endpoint was not statistically different across the spectrum of NT-proBNP (p-interaction = 0.46). Conclusions When assessed within the first week of a high risk AMI NT-proBNP is not only associated with incident HF and death but also with atherosclerotic events and provides prognostic information that is independent of hsTnT in this post AMI population. Funding Acknowledgement Type of funding sources: None.

A systematic review and meta-analysis of sacubitril-valsartan in the treatment of ventricular remodeling in patients with heart failure after acute myocardial infarction

“…Clinically, the adverse reactions with a higher incidence of ARNI and ACEI/ARB include hypotension, hyperkalemia, angioedema, cough, and liver and kidney dysfunction. in this study, 7 papers (14,18,19,22,24,27,28) described the incidence of hypotension (P < 0.00001, I 2 = 0%), 4 papers (14,18,22,27) described the incidence of hyperkalemia (P = 0.60, I 2 = 7%), 4 articles (14,18,19,27) describe the incidence of angioedema (P = 0.33, I 2 = 10%), 5 articles (14,18,22,27,28) describe the incidence of renal insufficiency (P = 0.94, I 2 = 0%), and 3 articles (14,22,24) described the incidence of cough (P < 0.00001, I 2 = 0%), and the incidence of overall adverse reactions was not statistically different (P = 0.16, I 2 = 71%). Subgroup analysis showed that the heterogeneity of the total adverse event rate was derived from different clinical symptoms, and the homogeneity among subgroups was good.…”

“…The quality of the included studies was relatively high. Of these, three studies were assigned at the discretion of the clinician (18,19,28), two studies used an interactive web for grouping and assignment concealment (14,21), and two studies used sealed envelopes for randomization and assignment concealment (15, 20), three studies used random number tables for randomization (25,26,29). The remaining studies mentioned randomization but did not mention the specific method and did not mention allocation concealment in the text.…”

“…The remaining studies mentioned randomization but did not mention the specific method and did not mention allocation concealment in the text. Three studies were multicenter, double-blind trials (14,17,21). Although patients, experimenters, and outcome assessors were not blinded in the remaining trials, the judgment of outcome indicators would not be affected by the unblinded method.…”

“…We summarized cardiac death, recurrent myocardial infarction, hospitalization for recurrent heart failure, and malignant arrhythmia as adverse cardiovascular events. Among them, 5 articles (14,19,20,22,28) describe the incidence of cardiac death, and 6 articles (19,20,22,(27)(28)(29) describe the incidence of recurrent myocardial infarction, 9 articles (14, 18-20, 22, 24, 25, 28, 29) describe the incidence of hospitalization for recurrent heart failure, 3 articles (22, 24, 28) describe the incidence of malignant arrhythmia describe. The heterogeneity among the studies was small, and a fixedeffects model was used for Meta.…”

“…In the sizeable PARADIGM-HF trial, sacubitril-valsartan reduced the number of hospitalizations for heart failure and decreased mortality in patients with chronic HFrEF compared with conventional ACEI/ARB (13). The latest RCT (PARADISE-MI) showed that sacubitril-valsartan compared with ramipril did not significantly reduce the incidence of heart failure or cardiovascular death after myocardial infarction, but it still has further improvements (14). There are now a sufficient number of controlled trials demonstrating the efficacy of sacubitrilvalsartan in the treatment of myocardial infarction with heart failure.…”