New diabetes treatment also improves heart failure outcomes

Fitchett D, Zinman B, Wanner C, et al.
Eur Heart J 2016; published online ahead of print

Background

Effective management of type 2 diabetes (T2DM) in patients with heart failure (HF) has been challenging, since there has been no evidence so far showing improved HF outcomes with intensive glucose control using existing glucose-lowering medications [1,2]. Recent guidelines have recognised the fact that there is no adequate evidence regarding the safety and efficacy of drugs used to treat diabetes in patients with HF [3,4].
Empagliflozin is a selective inhibitor of the sodium glucose cotransporter 2 (SGLT2) that reduces renal glucose reabsorption, increases urinary glucose excretion, and is associated with osmotic diuresis, reductions in weight and blood pressure, and improvements of markers of arterial stiffness and vascular resistance, albuminuria, and serum uric acid [5-7].
In patients with T2DM and high cardiovascular (CV) risk, empagliflozin, on top of standard of care, reduced the primary composite outcome of CV death, non-fatal myocardial infarction or non-fatal stroke, as well as hospitalisation rates for HF and overall mortality compared with placebo (EMPA-REG OUTCOME trial) [8]. Approximately 10% of T2DM patients in this study had HF at baseline. The present report provides data on HF-specific outcomes of the EMPA-REG OUTCOME trial.

Main results

• Empagliflozin, compared with placebo improved:

• the composite outcome of HF hospitalisation or CV death: 5.7 vs. 8.5%; HR: 0.66; 95% CI: 0.55–0.79; P < 0.001, NNT to prevent one HF hospitalisation or CV death: 35 over 3 years
• all-cause hospitalisation: 36.8 vs. 39.6%; HR: 0.89; 95% CI: 0.82–0.96; P = 0.003
• hospitalisation for HF: 2.7 vs 4.1%; HR: 0.65; 95% CI: 0.50–0.85; P = 0.002
• hospitalisation for or death from HF: 2.8 vs. 4.5%; HR: 0.61; 95% CI: 0.47–0.79; P < 0.001

• Empagliflozin and use of loop diuretics:

• loop diuretics were introduced in a significantly lower proportion of patients in the empagliflozin group than the placebo group (HR: 0.62; 95% CI: 0.53–0.73; P < 0.001)
• empagliflozin reduced the risk of the composite outcomes of hospitalisation for HF or introduction of loop diuretics (HR: 0.63; 95% CI: 0.54–0.73; P < 0.001)
• empagliflozin reduced the risk of HF hospitalisation or CV death or introduction of loop diuretics (HR: 0.64; 95% CI: 0.56–0.73; P < 0.001)

• In patients with HF vs. patients without HF at baseline, incidence rates for

• HF hospitalisation or CV death were 16.2 vs. 4.5%
• hospitalisation for HF were 10.4 vs. 1.8%
• CV death were 8.2 vs. 3.2%
• all-cause mortality were 12.1 vs 5.0%

• Serious adverse events and adverse events leading to discontinuation were reported by a higher proportion of patients with vs. without HF at baseline in both treatment groups, but were no more common with empagliflozin than with placebo.

Conclusion

Empagliflozin, on top of standard of care, reduced HF hospitalisation and CV death in patients with T2DM and high CV risk. Moreover, there was a lower rate of introduction of loop diuretics in the empagliflozin group. The observed benefit was consistent in patients with and without HF at baseline. These findings are of particular importance, given the lack of adequate evidence regarding the safety and efficacy of drugs used to treat diabetes in patients with HF.

Find this article online at Eur Heart J

References

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