Consistent cardiovascular (CV) benefit of empagliflozin over the spectrum of CV risk factor control in EMPA-REG OUTCOME

Abstract

Background: In EMPA-REG OUTCOME trial of 7020 patients with Type 2 diabetes and CV disease, empagliflozin significantly reduced risk for 3P-MACE (CV death, non-fatal myocardial infarction, or non-fatal stroke), CV death, hospitalization for heart failure (HHF) and the HHF or CV death composite, versus placebo. We explored these outcomes based on achievement of seven CV risk-factor goals (HbA1c <7.5%; low-density lipoprotein-cholesterol <100 mg/dL or statin use; systolic blood pressure <140 and diastolic blood pressure <90 mmHg; angiotensin-converting-enzyme inhibitor/angiotensin-II-receptor blocker use; normoalbuminuria; aspirin use; non-smoking status) at baseline. Methods: Patients were classified into groups according to achievement of 0–3, 4–5 or 6–7 CV risk factor goals. Cox proportional hazards models were used to investigate the consistency of treatment effect across subgroups. Results: Within the placebo group, hazard ratio (HR) for 3P-MACE was 2.21 (95% confidence interval 1.53–3.19) and 1.42 (1.06–1.89) for patients achieving 0–3 or 4–5 risk factor goals, respectively, versus 6–7. Patients achieving 0–3 or 4–5 goals had increased risk for CV death (HR 4.00 [2.26–7.11] and 2.48 [1.52–4.06], respectively) and HHF or CV death (HR 2.89 [1.82–4.57] and 1.90 [1.31–2.78]), with a non-significant trend for HHF (HR 1.91 [0.96–3.79] and 1.67 [1.00–2.80]) versus 6–7 goals. Empagliflozin reduced risk for these events versus placebo across all subgroups (p for interaction=non-significant). Conclusions: CV risk increases with fewer CV risk factors controlled, but the cardioprotective effect of empagliflozin was consistent regardless of baseline risk-factor control.