Background: In EMPA-REG OUTCOME, empagliflozin given in addition to standard of care significantly reduced 3-point major adverse cardiovascular (CV) events (3-point MACE: composite of CV death, non-fatal myocardial infarction, non-fatal stroke) (HR 0.86 [95% CI 0.74, 0.99]), CV death (0.62 [0.49, 0.77]), all-cause mortality (0.68 [0.57, 0.82]), and hospitalization for heart failure (HHF) (0.65 [0.50, 0.85]) vs placebo in patients with type 2 diabetes (T2DM) and established CV disease. 

Aim: To investigate CV outcomes and all-cause mortality by smoking status at baseline. 

Methods: Patients were randomized to receive placebo, empagliflozin 10 mg, or empagliflozin 25 mg. Differences in risk of CV outcomes and all-cause mortality between empagliflozin and placebo across subgroups by baseline smoking status (never smoked, ex-smoker, current smoker) were assessed using a Cox proportional hazards model including a subgroup-by-treatment interaction term.

Results: In total, 2333, 2345 and 2342 patients received placebo, empagliflozin 10 mg and empagliflozin 25 mg, of whom 1074 (46.0%), 1052 (44.9%) and 1083 (46.2%) were ex-smokers, and 302 (12.9%), 325 (13.9%) and 302 (12.9%) were current smokers at baseline, respectively. The benefits of empagliflozin vs placebo on 3-point MACE, CV death, all-cause mortality and HHF were consistent regardless of smoking status at baseline. 

Discussion: In patients with T2DM and established CV disease, empagliflozin reduced the risk of CV outcomes and mortality irrespective of smoking status at baseline.

EMPA-REG OUTCOME: Empagliflozin reduced the risk of cardiovascular outcomes irrespective of smoking status