A New Perspective on Lowering CV Risk From Hypoglycaemia

Carolina Solis-Herrera; Omar Sheikh; Robert Chilton


Eur Heart J. 2020;41(2):218-220. 

In This Article

Abstract and Introduction


Fitchett et al., in this issue of the European Heart Journal, present a post-hoc exploratory analysis of the EMPA-REG Outcome trial[1] for the relationship between hypoglycaemia and cardiovascular (CV) outcomes.[2] Investigator-reported hypoglyceamia was defined as HYPO-strict (plasma glucose <54 mg/dL or severe hypoglycaemia, defined by needed assistance for treatment) and HYPO-broad (symptomatic hypoglycaemia with plasma glucose <70 mg/dL, any hypoglycaemia with plasma glucose <54 mg/dL, or severe hypoglycaemia).

Out of 7020 participants, 28% experienced an episode of HYPO-broad (empagliflozin 27.9% vs. placebo 28.2%), whereas 18.8% experienced an episode of HYPO-strict (empagliflozin 18.8% vs. placebo 18.9%). The time to occurrence of HYPO-strict or HYPO-broad did not significantly differ between groups. More subjects with a history of HYPO-strict or HYPO-broad tended to have baseline characteristic(s) of longer duration of disease, more frequent microvascular disease, and insulin therapy.

In the placebo group, any hypoglycaemic event prior to a subsequent CV event was analysed. The occurrence of HYPO-broad was associated with a higher risk of fatal/non-fatal myocardial infarction (MI) [hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.06–2.29] and hospitalization for heart failure (HF) (HR 1.91, 95% CI 1.25–2.93), whereas for those who experienced HYPO-strict, only HF was significantly increased (HR 1.72, 95% CI 1.06–2.78).

Hypoglycaemia in this post-hoc analysis was associated with an increased risk of HF and MI in the placebo group. Despite no difference in rates of hypoglycaemia, when empagliflozin was compared with placebo, the CV outcome reductions in both HYPO-broad [18%, three-point major adverse CV events (3P-MACE); 37%, all-cause mortality; 50%, CV death; 50%, HF] and HYPO-strict (7%, 3P-MACE; 45%, all-cause mortality; 44%, CV death; 38%, HF) were not attenuated by hypoglycaemia.