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

Sodium-glucose cotransporter 2 inhibitors associated with cardiovascular benefits

26th January 2022

Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) reduce adverse cardiovascular outcomes according to a meta-analysis of clinical trials

SGLT2-Is can be considered as an effective class of drugs to improve cardiovascular morbidity and mortality. This was the conclusion of a meta-analysis by researchers from the Division of Cardiology, Southern Illinois University School of Medicine, US.

SGLT2-Is were developed and licensed as a class of drugs for the management of type 2 diabetes and one agent in particular, dapagliflozin, has been shown, as an add-on drug to conventional anti-diabetic drugs, to improve glycaemic control. However, with more widespread use of these drugs, it became apparent that there were potential cardioprotective effects, such as a reduction in the worsening of heart failure, irrespective of whether or not the patients were diabetic.

For the present study, the US researchers, set out to establish whether the magnitude of any cardiovascular benefit from SGLT2-Is were generalisable to patients of different ages and ethnicities. They searched for placebo-controlled randomised clinical trials in patients with existing atherosclerotic cardiovascular disease (ASCVD) or the presence of risk factors for ASCVD such as diabetes or heart failure.

They set the primary outcome as cardiovascular death or hospitalisation for heart failure (HHF) and major cardiovascular events (MACE), HHF, cardiovascular death, acute myocardial infarction and all-cause mortality as secondary outcomes. They included gender, age (< 65 or > 65) and ethnicity as subgroups for separate analyses.

Findings

A total of 10 trials including 71,553 patients were analysed with 39,053 who received SGLT2-Is.

The primary outcome of cardiovascular death or HHF was reported in all trials and there were 6921 incidents, 8.1% occurring in those given SGLT2-Is and 11.6% in the placebo group. The use of SGLT2-Is was calculated to be associated with 33% reduced risk of the primary outcome (odds ratio, OR = 0.67, 95% CI 0.55 – 0.80, p < 0.01).

There was also a reduced risk of MACE in those taking SGLT2-Is (OR = 0.90, 95% CI 0.81 – 0.99, p = 0.03). However, there was no difference in the rate of acute myocardial infarction in those taking SGLT2-Is compared to placebo (OR = 0.95, 95% CI 0.87 – 1.03). Moreover, subgroup analysis favoured the use of SGLT2-Is in all groups compared and all-cause mortality was also lower in those taking SGLT2-Is (OR = 0.87, 95% CI 0.80 – 0.96, p = 0.04).

The authors concluded that the ‘cardiovascular outcomes of SGLT2-I therapy can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled.’

Citation

Bhattarai M et al. Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Patients With Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease: A Meta-analysis. JAMA 2022