SGLT2 inhibitor reduced HF outcomes independently of HF risk in diabetic patients
Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOME trialLiterature - Fitchett D, Butler J, van de Borne P, et al, on behalf of the EMPA-REG OUTCOME trial investigators - Eur Heart J 2017; published online ahead of print
- The incident HF hospitalization rate or CV death risk per 100 patient-years (PY) in the placebo group increased with increasing HF risk profile (1.68 in the low-to-average risk group; 95%CI: 1.31 - 2.10; 4.03 in the high-risk group; 95%CI: 3.06 - 5.13; 7.0 in the very-high risk group; 95%CI: 4.33 - 10.29). In comparison, the incident HF hospitalization rate or CV death risk in those with prevalent baseline HF was 8.55 (95%CI: 6.33 - 11.11) per 100 PY.
- In those without HF at baseline, regardless of their HF risk category, empagliflozin reduced the risk of HF hospitalization and CV death, as well as the individual components. A separation of the cumulative incidence curves appeared early and the reduction of risk persisted for the duration of the trial.
- The CV mortality was also significantly reduced among the 13.6% (958 patients) in the trial with HF burden (HR: 0.67; 95% CI: 0.47 - 0.97), in whom absolute risk reduction was 4.9%.
- The magnitude of relative benefit was similar in the 86.4% of patients without HF burden (HR: 0.63; 95% CI: 0.48–0.84) at baseline or during the trial.
- The total number of deaths in the baseline or incident HF population comprised 37.9% of the overall CV deaths, whereas 62.1% occurred in the population without any HF burden.
- Reductions in the risk for HF hospitalization with empagliflozin vs. placebo were observed by the first month and persisted for the duration of the trial. The HR stabilized as the number of patients with events increased over time.
Many T2DM patients with established CVD and without HF are at high or very high risk for HF outcomes. Empagliflozin reduced adverse HF outcomes both in patients at low or high HF risk.
In his editorial article, Paneni  comments on the paper of Fitchett et al: ‘Taken together, these findings show for the first time that an SGLT-2 inhibitor, namely empagliflozin, reduces CV mortality and HHF in patients at both high and lower risk, as well as in patients with or without either baseline or incident HF.’
The author discusses the possible mechanisms leading to the reduction of CV mortality and HF hospitalization with empagliflozin, including osmotic diuresis, reduction in sympathetic nerve activation and increase of circulating ketone bodies, and he concludes: ‘Notably, the effect of SGLT-2 inhibitors on glucose elimination is proportional to glycaemic levels, being modest or even negligible in conditions of mild hyperglycaemia. This ‘self-limiting’ action of SGLT-2 inhibitors may suggest their use also in patients without diabetes (i.e. pre-diabetes, obesity, hypertension) to prevent adverse cardiac remodelling and dysfunction. Future studies will help us to characterize further and appreciate the potential of empagliflozin and other SGLT-2 inhibitors to fight the epidemic of HF.’