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20th April 2022
Heart failure (HF) is typically described as either left ventricular systolic or diastolic dysfunction and multiple studies have correlated the elevation of pro-inflammatory cytokines with a worse prognosis. In fact, increased levels of plasma interleukin-6 (IL-6) concentrations are frequently observed in patients with acute heart failure and which have prognostic value. Additionally, other work suggests that a modestly elevated CRP level upon discharge had unique long-term prognostic implications among hospitalised patients with acute heart failure. However, whether the use of anti-inflammatory agents is of value in those with heart failure is uncertain, although some evidence suggests that, despite suppression of the inflammatory markers CRP and IL-6, anti-inflammatory agents, such as infliximab, do not improve the clinical condition of patients with moderate-to-severe chronic heart failure.
Using data from the Epidemiology of Acute Heart Failure in the Emergency Departments (EAHFE) registry, researchers examined the outcomes for a subset of patients whose blood results were suggestive of inflammation, i.e., N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels > 300pg/ml and CRP levels > 5mg/ml. The team then divided patients into two groups based on whether they received systemic corticosteroids in the ED or not. For the analysis, the primary outcome was 30-day all-cause mortality with secondary outcomes including in-hospital, all-cause mortality and a 30-day post-discharge composite of ED revisits, hospitalisation or death. They also undertook a subgroup analysis based on CRP levels.
Corticosteroid use and HF outcomes
A total of 1109 patients with an overall mean age of 81.2 years (45% male) were included in the study, of whom, 121 (10.9%) received at least one IV bolus of corticosteroids during their ED stay.
In patients with CRP levels > 5mg/l and NT-proBNP levels > 300pg/ml, the cumulative risk of 30-day all-cause mortality was not significantly different to those who did not receive corticosteroids (HR = 1.26, 95% CI 0.75 – 2.09, p = 0.38).
However, as levels of CRP increased and after adjustment for the EAHFE score (which predicts short-term prognosis), the hazard ratios reduced, although remained non-significant. For example, in patients with highly elevated CRP levels (> 40mg/l and NT-proBNP levels > 300) the adjusted HR for 30-day all-cause mortality was 0.56 (95% CI 0.20 – 1.55, p = 0.27) and, while not significant, this was 7.7% lower in corticosteroid-treated patients.
The authors concluded that their analysis suggested that corticosteroid use in those with acute heart failure might have the potential to improve outcomes, especially among those with inflammatory activation, but further larger, prospective studies should be considered to assess any potential in patients with the highest degree of inflammation.
Miro O et al. Effect of systemic corticosteroid therapy for acute heart failure patients with elevated C‐reactive protein ESC Heart Fail 2022
14th March 2022
Empagliflozin administered to patients once hospitalised with either de novo or decompensated heart failure leads to a clinically significant benefit over the next 90 days. This was the finding of a randomised trial by researchers from the University of Groningen Department of Cardiology, Groningen, The Netherlands.
Among patients with type 2 diabetes, sodium–glucose cotransporter 2 inhibitors such as empagliflozin, have been shown to reduce the risk of hospitalisation for heart failure and the risk of serious adverse renal events. Although an anti-diabetic agent and based on several recent clinical trials, empagliflozin is now also indicated for the treatment of symptomatic chronic heart failure with a reduced ejection fraction.
However, whether the drug would still provide a clinical benefit to patients if given to those already admitted to hospital with heart failure is unknown. For the present study, the Dutch researchers were interested in exploring whether empagliflozin would be clinically advantageous for patients, not only hospitalisation with heart failure but also on reducing worsening heart failure events (HFEs) and on the improvement of symptoms. They performed the Oral EMPagliflozin 10 mg Compared to Placebo, Initiated in Patients Hospitalised for acUte Heart faiLure (de Novo or Decompensated Chronic HF) Who Have Been StabilisEd or EMPULSE trial.
Included patients were those who had a primary diagnosis of acute de novo or decompensated chronic heart failure, irrespective of left ventricular ejection fraction. Individuals were randomised 1:1 to empagliflozin 10 mg or placebo and this occurred after at least 24 hours but no later than 5 days after admission, as early as possible after stabilisation and while still in hospital. The primary outcome of the study was the clinical benefit at 90 days, which was defined as a composite outcome of time to all-cause death, the number of HFEs, the time to the first HFE and a 5- point or greater difference in change from baseline in Kansas City Cardiomyopathy Questionnaire KCCQ after 90 days of treatment. The KCCQ is patient-reported outcome instrument that provides a measure of symptoms and physical limitations associated with heart failure. Assessments were based on the win ratio, which offers greater statistical power to detect and quantify a treatment difference by using all available information contained in the component outcomes.
Empagliflozin and clinical outcomes
A total of 530 patients with a median age of 71 years (34% women) were randomised to active treatment or placebo, within a median of 3 days after admission to hospital. The proportion of patients with diabetes ranged from 46.8% to 43.8%.
Overall, 33 (6.2%) of all patients died, 11 in the empagliflozin group and there were 67 patients assigned to empagliflozin who experienced at least one HFE. The adjusted mean change in KCCQ total score from baseline to 90 days was 36.2 in the empagliflozin group and 31.7 in the placebo arm. More patients taking empagliflozin had a clinical benefit compared to placebo (stratified win ratio = 1.36, 95% CI 1.09 – 1.68, p = 0.0054). This benefit was observed irrespective of the ejection fraction and for both de novo and decompensated heart failure in the presence or absence of diabetes.
The authors concluded that initiating empagliflozin as a component of usual clinical care for patients hospitalised with acute heart failure led to clinically meaningful benefits.
Voors AA et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med 2022