Evaluation of the effect of intravenous nitroglycerine on short-term survival of patients with acute heart failure according to congestion and perfusion status at emergency department arrival

Abstract

Objectives: We investigated if the phenotypic classification of acute heart failure (AHF) based on the number of signs/ symptoms of congestion and hypoperfusion at emergency department (ED) arrival identifies subgroups in which intravenous (IV) nitroglycerine (NTG) use improves shortterm survival.Methods: We included consecutive AHF patients diagnosed in 45 Spanish EDs, who were grouped according to phenotype severity. The main outcome was 30-day all-cause death. Propensity scores (PS) for NTG use were generated using variables associated with death. Analysis of interaction was performed in subgroups of patients based on congestion, hypoperfusion, age, sex, coronary artery disease (CAD), left ventricular ejection fraction (LVEF) and SBP.Results: We analyzed 16 437 AHF patients (median = 83 years; women = 56%); 1882 received NTG (11.4%). In the whole cohort, the cumulative 30-day mortality in patients receiving NTG was higher (11.5% vs. 9.6%; unadjusted HR, 1.19; 95% CI, 1.04-1.36), but not in the PS-matched cohorts (1698 pairs of patients; 11.5% vs. 10.5%; HR, 1.10; 95% CI, 0.90-1.35). Mortality was increased in NTG-treated patients with mild congestion (HR, 2.09; 95% CI, 1.19-3.67), especially in those without hypoperfusion (HR, 2.51; 95% CI, 1.24-5.10). Interaction analysis of the PS-matched cohorts confirmed detrimental effects of NTG use in less congested patients, whereas beneficial effects were only observed in patients with decreased LVEF (<50% subgroup: HR, 0.59; 95% CI, 0.37-0.92; ≥50% subgroup: HR, 1.30; 95% CI, 0.66-2.56; P = 0.002). Conclusion: Phenotypical classification of AHF based on congestion/ hypoperfusion at ED arrival does not identify subgroups of patients in whom IV-NTG would decrease mortality, although it could potentially be beneficial in those with LVEF of less than 50%. This hypothesis will have to be confirmed in the future. Conversely, our results suggest that IV-NTG may be harmful in patients with only mild clinical congestion.

Causal inference from observational data in emergency medicine research

“…Miró et al . [9] used the propensity score method to assess the effect of intravenous nitroglycerin on survival of patients with acute heart failure. The same approach was used to assess the effect of adrenaline dose on neurological outcomes after out-of-hospital cardiac arrest [10].…”

“…This propensity score is thereafter used as a matching criterion, stratification or an adjustment factor for assessing the association between intervention and outcome. Miró et al [9] used the propensity score method to assess the effect of intravenous nitroglycerin on survival of patients with acute heart failure. The same approach was used to assess the effect of adrenaline dose on neurological outcomes after out-of-hospital cardiac arrest [10].…”

Morphine in acute pulmonary oedema: a signal of harm but more questions than answers

“…However, most of the evidence is derived from mega‐trials conducted in general AHF populations, not entirely generalizable to the APO clinical profile 4 . In addition, none of the studied interventions showed simultaneous benefit for symptomatic relief and increased survival 5–7 …”

“…4 In addition, none of the studied interventions showed simultaneous benefit for symptomatic relief and increased survival. [5][6][7] Morphine is still used in patients with APO based predominantly on its beneficial haemodynamic effects (reduction in pre-and afterload) and those on the central nervous system (improvement in patient anxiety, respiratory difficulty and chest pain). However, randomized controlled trials have not provided persuasive evidence of clinical benefit for its use in patients with APO.…”

Acute heart failure in emergency departments: what is new in 2023?

“…Other treatments of the congestion like intravenous nitrate are still recommended with a moderate level of evidence [9][10][11]. Nevertheless, a recent study failed to prove the impact of a care bundle compared with standard care [2].…”