Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial

Abstract

Aims: We previously reported that in the EMPA-REG OUTCOME(®) trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular events, cardiovascular and all-cause death, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. We have now further investigated heart failure outcomes in all patients and in subgroups, including patients with or without baseline heart failure.

Methods and results: Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Seven thousand and twenty patients were treated; 706 (10.1%) had heart failure at baseline. Heart failure hospitalization or cardiovascular death occurred in a significantly lower percentage of patients treated with empagliflozin [265/4687 patients (5.7%)] than with placebo [198/2333 patients (8.5%)] [hazard ratio, HR: 0.66 (95% confidence interval: 0.55-0.79); P < 0.001], corresponding to a number needed to treat to prevent one heart failure hospitalization or cardiovascular death of 35 over 3 years. Consistent effects of empagliflozin were observed across subgroups defined by baseline characteristics, including patients with vs. without heart failure, and across categories of medications to treat diabetes and/or heart failure. Empagliflozin improved other heart failure outcomes, including hospitalization for or death from heart failure [2.8 vs. 4.5%; HR: 0.61 (0.47-0.79); P < 0.001] and was associated with a reduction in all-cause hospitalization [36.8 vs. 39.6%; HR: 0.89 (0.82-0.96); P = 0.003]. Serious adverse events and adverse events leading to discontinuation were reported by a higher proportion of patients with vs. without heart failure at baseline in both treatment groups, but were no more common with empagliflozin than with placebo.

Conclusion: In patients with type 2 diabetes and high cardiovascular risk, empagliflozin reduced heart failure hospitalization and cardiovascular death, with a consistent benefit in patients with and without baseline heart failure.

Keywords: Cardiovascular disease; Hospitalization; Mortality.

Figure 1

(A) Time to first hospitalization for heart failure or cardiovascular death. (B) Time to first all-cause hospitalization. Cumulative incidence function. Patients treated with at least one dose of study drug. HR, hazard ratio; CI, confidence interval.

Figure 2

Subgroup analyses of heart failure hospitalization or cardiovascular death and hospitalization for heart failure by baseline characteristics. Patients treated with at least one dose of study drug. ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CI, confidence interval; DBP, diastolic blood pressure; HbA1c, glycated haemoglobin; HR, hazard ratio; SBP, systolic blood pressure.

Figure 3

Outcomes in patients with and without heart failure at baseline. Cox regression analysis. Patients treated with at least one dose of study drug. CI, confidence interval; HR, hazard ratio.