EMPA-REG OUTCOME: Impact of Empagliflozin on CV Outcomes as per Baseline LDL-C Levels
Introduction
The significant association between high levels of low-density lipoprotein-cholesterol (LDL-C) and increased cardiovascular (CV) risk is already well-established. The EMPA-REG OUTCOME (Empagliflozin cardiovascular outcome event trial in type-2 diabetes mellitus patients) has already demonstrated that empagliflozin, a sodium glucose cotransporter-2 inhibitor (SGLT2-i); when added to the treatment regimen of type-2 diabetes mellitus (T2DM) patients with established CV disease reduced the risk of major adverse cardiovascular events (MACE) and the risk of hospitalization for heart failure (HHF). Nevertheless, it is not known if these CV benefits of empagliflozin would be consistent across various LDL-C categories.
Aim
To determine the impact of empagliflozin on CV outcomes as per the baseline LDL-C levels in EMPA-REG OUTCOME
Patient Profile
- Type-2 diabetes mellitus patients with glycosylated hemoglobin (HbA1c) 7.0%-9.0%, if drug na?ve and HBA1c 7.0%-10.0% if already on stable glucose-lowering therapy (n=7020)
- All the study subjects had established CV disease and estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2
- Based on the baseline LDL-C levels patients were grouped as:
- <70 mg/dL
- 70–<85 mg/dL
- 85–<100 mg/dL
- 100–115 mg/dL
- >115 mg/dL
Methods
Study Design
- A post hoc analysis of EMPA-REG OUTCOME trial
- EMPA-REG OUTCOME was a randomized, double-blind, multi-center clinical trial conducted across Europe, North America and Asia
Treatment Strategy
- Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo
Outcome
- 3 point (3P)-MACE (death from CV causes, nonfatal myocardial infarction, or nonfatal stroke)
- CV death
- HHF
- All-cause mortality
Follow-up Period
- Median: 3.1 years
Results
- Of the entire study population, 81.0% received lipid lowering therapy (77.0% statins). Mean LDL-C was 85 mg/dL (2.2), and 38% and 18% patients had LDL-C <69.6 mg/dL and 116 mg/dL, respectively.
- Demographics such as, age, body mass index (BMI), and HbA1c levels were balanced between various LDL-C subgroups, though the prevalence of coronary artery disease (83.0% vs. 59.9%) and the use of statins (88.2% vs. 50.9%) was higher in the lowest vs. highest LDL-C subgroups.
- Overall, empagliflozin consistently reduced all outcomes considered during the study, across LDL-C categories (all interaction p-values > 0.05).
Conclusions
- The beneficial CV effects of empagliflozin remained consistent irrespective of the baseline LDL-C in T2DM patients
- A relatively high CV event rate and a low prevalence of statin use among patients with the highest baseline LDL-C subgroups highlights the importance of aggressive lipid-lowering therapy in patients with high CV risk.
Diabetes Vasc Dis Res. 2020 Nov-Dec;17(6):1479164120975256. doi: 10.1177/1479164120975256.
