BACKGROUND: In the EMPA-REG OUTCOME trial in patients with type 2 diabetes and established CV disease, empagliflozin reduced the risk of 3-point MACE (composite of CV death, MI, or stroke) by 14%, CV death by 38% and hospitalisation for heart failure (HHF) by 35% vs placebo in analyses of time to first event. We assessed the effect of empagliflozin on all (first and recurrent) CV events.
METHODS: Patients were randomised to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo in addition to standard of care. We assessed the effects of empagliflozin pooled vs placebo based on all adjudicated CV events using a negative binomial model with confidence intervals based on robust error variance estimators to account for within-subject correlation.
RESULTS: A total of 7020 patients were treated (mean [SD] age 63  years, 71% male, 47% with history of MI, 23% with history of stroke, 10% with HF). In analyses including all events, the event rate ratio (95% CI) with empagliflozin vs placebo was 0.78 (0.67, 0.91; p=0.0020) for 3-point MACE, 0.79 (0.620, 0.998; p=0.0486) for MI, 1.10 (0.82, 1.49; p=0.5248) for stroke, 0.58 (0.42, 0.81; p=0.0012) for HHF, 0.56 (0.45, 0.69; p<0.0001) for the composite of CV death or HHF, and 0.80 (0.67, 0.95; p=0.0119) for the composite of MI or coronary revascularisation. Results were consistent with analyses of first events.
CONCLUSIONS: Analyses of all (first and recurrent) CV events in the EMPA-REG OUTCOME trial complement previous analyses and confirm the consistency of the results.