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20th April 2022
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.
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
14th February 2022
Rates of re-hospitalisation and mortality among people who were originally admitted to hospital with an acute COVID-19 infection, appear to be much higher than those hospitalised with other conditions.
This was the key finding from an analysis of information in the OPENSAFELY database by researchers at the Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
During the early stages of the COVID-19 pandemic, although many patients were initially managed in an outpatient settings, one study found that 15% of cases required hospitalisation and 4% died within a month of first symptoms.
The introduction of COVID-19 vaccines have been effective at preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations. Nevertheless, there is little currently known about the subsequent outcomes for those patients who were initially hospitalised because of COVID-19, although where such data does exist, it appears that patients are still at risk of future adverse outcomes.
For example, in one US study it was found that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Similarly, a UK-based study concluded that individuals discharged from hospital after COVID-19 had increased rates of multi-organ dysfunction compared with the expected risk in the general population.
For the present study, the UK team decided to examine the incidence of subsequent re-hospitalisation and death in those initially admitted to hospital with COVID-19 in comparison to both the general population and those who were hospitalised prior to the pandemic, with influenza.
They used the OPENSAFELY platform which provides information from primary care practices and linked patient information with other databases providing data on hospitalisations and mortality. Their main outcomes of interest were re-hospitalisation or death and all-cause mortality. The team used regression models which were adjusted for a number of covariates such as age, sex, ethnicity, obesity and other co-morbidities.
Re-hospitalisation and mortality after acute COVID-19
The analysis included 24,673 individuals discharged from hospital after a COVID-19 hospitalisation and who were matched with 123,362 controls and 16,058 patients who had been hospitalised and discharged due to influenza. COVID-19 patients had a median age of 66 years (55.7% male) which was slightly younger than the median age of those hospitalised due to influenza (69 years).
The overall risk of re-hospitalisation was higher in the discharged COVID-19 group compared to the general population (adjusted hazard ratio, aHR = 2.22, 95% CI 2.14 – 2.30, p < 0.001). However, the risk of re-hospitalisation was lower than the influenza group (aHR = 0.95, 95% CI 0.91 – 0.98, p = 0.004).
All-cause mortality was higher in the COVID-19 discharged group than in the general population (aHR = 4.82, 95% CI 4.48 – 5.19, p < 0.001) and for the influenza group (aHR = 1.74, 95% 1.61 – 1.88, p < 0.001).
When examining the reported cause of death, 24.7% of deaths had COVID-19 listed as the cause although in comparison, less than 5 deaths were reportedly due to influenza.
The authors concluded that among patients who survived hospitalisation after an acute infection with COVID-19, there was a substantially higher risk of subsequent re-hospitalisation and death over the next 10 months.
They suggested that these findings highlighted a need for services to support and closely monitor people following discharge from hospital.
Bhaskaran K et al. Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care, secondary care, and death registration data in the OpenSAFELY platform. PLos Med 2022