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Meta-analysis finds sodium-glucose co-transporter-2 inhibitors reduce adverse CV outcomes in acute decompensated heart failure

20th April 2022

Sodium-glucose co-transporter-2 inhibitors reduce adverse cardiovascular outcomes in patients with acute decompensated heart failure

The use of sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) in patients with acute, decompensated heart failure is associated with a reduction in adverse cardiovascular outcomes compared with placebo. However, these improvements do not translate into a significant reduction in all-cause mortality, as concluded by a meta-analysis of trials by researchers from the University of Thessaloniki, General Hospital “Hippokration,” Thessaloniki, Greece.

Heart failure (HF) is a complex clinical syndrome characterised by the reduced ability of the heart to pump and/or fill with blood failure. Heart failure is a common problem and globally, the age-standardised prevalence of HF in 2017 was 831.0 per 100,000 people. Moreover, the prognosis of those with more severe HF is poor, with one study finding that among patients hospitalised with HF, the 1-year mortality rate was only 40%.

The sodium-glucose co-transporter 2 receptors are primarily located in the proximal convoluted tubule of the nephron and are responsible for almost 90% to 95% of tubular reabsorption of glucose in the nephron. The SGLT-2Is are a class of drugs originally designed for the management of type 2 diabetes (by preventing glucose re-uptake) although research over the last decade has found that the drugs also have beneficial effects in heart failure. As a result, some members of this class such as empagliflozin, are also licensed in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction.

However, whether these drugs are also effective in patients with acute decompensated HF remains to be determined and was the subject of the meta-analysis by the Greek researchers. The team searched for randomised, controlled trials that enrolled adult patients, irrespective or whether they had diabetes, and who were assigned to a SGLT-2I or placebo or an active comparator. They set the primary safety endpoint as the effect of SGLT-2I on recurrent worsening heart failure (WHF). Several secondary endpoints were used: all-cause mortality; a composite of cardiovascular death or recurrent hospitalisation for HF decompensation and finally, the observed diuretic response. This latter endpoint was defined as the weight change per standard loop diuretic dose. The effects of treatment were assessed using risk ratios (RR).

Sodium-glucose co-transporter-2 inhibitors and heart failure outcomes

The researchers only identified three relevant clinical trials including 1,831 patients.

Compared with placebo, the use of SGLT-2Is produced a signification reduction in the risk of WHF (RR = 0.66, 95% CI 0.58 – 0.76, p < 0.00001). Similarly, there was also a significant 30% reduced risk of the composite endpoint of cardiovascular death or re-hospitalisation for decompensated HF (RR = 0.70, 95% CI 0.62 – 0.78, p < 0.00001). Interestingly, despite these benefits, there was no significant effect on all-cause mortality (RR = 0.72, 95% CI 0.48 – 1.09, p = 0.12) and a non-significant effect on diuretic response, mean difference = – 1.15 (95% CI -3.18 to 0.17, p = 0.26).

Based on their findings, the authors concluded that their data indicated how the use of SGLT-2I drugs significantly reduced recurrent worsening of HF but called for further trials to clarify whether these drugs should become part of the treatment algorithm for HF patients.

Citation
Patoulias D et al. Meta-Analysis Evaluating the Efficacy of Sodium-Glucose Co-Transporter-2 Inhibitors in Patients With Acute or Recently Decompensated Heart Failure Am J Cardiol 2022

Sex-related heart failure mortality influenced by left ventricular ejection fraction

4th January 2022

Sex-related differences in mortality in patients with heart failure hospitalisations appear to be affected by the left ventricular ejection fraction according to researchers from the Cardiology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain.

Although the risk of heart failure (HF) is similar between men and women, there are some notable sex-related differences, with men being predisposed to HF with reduced ejection fraction and women with preserved ejection fraction. Although there is some evidence that women with HF live longer than men, they experience more psychological and physical disability. However, much of the available data is derived from patients with stable HF and what is less clear, is if there are any sex-related prognostic differences among patients hospitalised following decompensated heart failure.

For the present study, the Spanish team retrospectively examined gender differences in mortality across the left ventricular ejection fraction spectrum in a cohort of patients after a hospitalisation for acute HF. The researchers used a multi-centre prospective registry of those hospitalised and collected demographics, medical history, laboratory and echocardiographic parameters and followed patients over a 6-month period. The primary study endpoints were all-cause, cardiovascular and HF-related mortality. Cardiovascular death was considered secondary to a worsening of HF, acute myocardial infarction, stroke or transient ischaemic attack, whereas HF-related deaths were considered secondary to a worsening of the HF or a sudden cardiac death.

Findings

A total of 4812 patients with a mean age of 74.2 years (46.6% women) were included in the analysis. The proportion of patients with a left ventricular ejection fraction (LVEF) of < 40%, 41 – 49% and > 50% was 31.5%, 14.3% and 54.2% respectively. Women were generally older with a mean age of 76.8 years compared to 71.9 years for men and had a higher preserved ejection fraction (70.5% vs 39.9%, female vs male, p < 0.001).

After 6 months, 645 (13.4%) of the patients had died with mortality rates of 13.3% and 13.5% (women vs men, p = 0.82) and there were no significant sex-related differences in all-cause mortality. Moreover, LVEF was not an independent predictor of mortality (HR = 1.02, 95% CI 0.99 – 1.05, p = 0.13). Similarly, rates of cardiovascular mortality were not different between the sexes. However, there was a significant interaction between sex and levels of LVEF (p for interaction = 0.030) and women had a significantly lower risk of cardiovascular mortality at lower LVEF levels (< 25%). There were also no differences between the sexes in HF-related mortality although as with cardiovascular mortality, there were differences across the levels of LVEF and women had a reduced risk of HR-related death. For example, compared to men, women had a reduced risk of HF death at a LVEF of < 43% (HR = 0.77, 95% CI 0.59 – 0.99) In contrast, this risk of death in women became higher as the LVEF increased above 80%.

Commenting on these findings, the authors noted that while sex was not a determinant of 6 month all-cause mortality, women had a lower risk of cardiovascular and HR-related mortality where the LVEF was < 25% and < 43% but higher where the LVEF was > 80%. They concluded that further work is required to confirm these findings and to evaluate the potential negative implications of a supra-normal LVEF in women with a preserved ejection fraction.

Citation

Santas E et al. Sex-Related Differences in Mortality Following Admission for Acute Heart Failure Across the Left Ventricular Ejection Fraction Spectrum J Am Heart Assoc 2021