Reduction of Risk of Hospitalizations for Heart Failure in Type 2 Diabetics

Study Progress, Population and Target Parameters

EMPA-REG OUTCOME was an international randomized placebo-controlled trial that included 7020 patients with type 2 diabetes (with HbA_1c 53–75 mmol/mol without antidiabetic treatment or with HbA_1c 53–86 mmol/mol on stable antidiabetic treatment) and known CV disease. As part of the study, patients were given either empagliflozin at a dose of 10 or 25 mg once daily or placebo in addition to their existing treatment.

The primary monitored parameter was composite and included death from CV causes, non-fatal myocardial infarction (MI), and non-fatal stroke. The median follow-up duration was 3.1 years.

Results

Primary Parameter

The incidence of the primary monitored parameter was significantly lower with empagliflozin treatment (10.5%) than with placebo (12.1%): hazard ratio (HR) 0.86; 95% confidence interval (CI) 0.74–0.99; p < 0.001 for non-inferiority and p = 0.04 for superiority of empagliflozin. In addition, treatment with empagliflozin was associated with a significant reduction in CV mortality (by 38%), overall mortality (by 32%), and hospitalizations for heart failure (by 35%).

Rate of Hospitalization

During the study, 4.1% of patients in the placebo group were hospitalized for heart failure compared to 2.7% of patients with empagliflozin. This corresponds to 14.5 hospitalizations for heart failure per 1000 patient-years with placebo and 9.4 hospitalizations for heart failure per 1000 patient-years with empagliflozin (HR 0.65; 95% CI 0.50–0.85; p = 0.002). The divergence in the curves illustrating hospitalization for heart failure occurred within the first months of treatment. A post-hoc analysis of this study also showed that the benefit of empagliflozin was similar in patients with and without a history of heart failure at study entry.

Fig. Hospitalizations for heart failure in the EMPA-REG OUTCOME study with empagliflozin treatment and placebo in patients with T2DM and high CV risk

Conclusion

The presence of type 2 diabetes represents a risk for the development of heart failure. Empagliflozin is the first antidiabetic medication that has been shown, in addition to reducing CV risk compared to placebo, to significantly decrease the incidence of hospitalizations for heart failure in patients with T2DM and known CV disease.

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Source: Zinman B., Wanner C., Lachin J. M. et al.; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373 (22): 2117–2128, doi: 10.1056/NEJMoa1504720.