Abstract
Objective:It is well established that higher low-density lipoprotein (LDL)-cholesterol levels are associated with increased cardiovascular risk. We analyzed whether effects of empagliflozin on cardiovascular outcomes varied by different LDL-cholesterol levels at baseline in EMPA-REG OUTCOME.Methods:Participants with type 2 diabetes and high cardiovascular risk received empagliflozin (10/25 mg) or placebo in addition to standard of care. We investigated the time to first 3P-MACE, cardiovascular death, hospitalization for heart failure (HHF) and all-cause mortality for empagliflozin versus placebo between baseline LDL-cholesterol categories <1.8, 1.8–<2.2, 2.2– <2.6, 2.6–3.0, and > 3.0 mmol/L, by a Cox regression including the interaction of baseline LDL-cholesterol category and treatment.Results:Of the 7020 participants randomized and treated, 81.0% received lipid lowering therapy (77.0% statins). Mean ± SD LDL-cholesterol was 2.2 ± 0.9 mmol/L, and 38%/18%, had LDL-cholesterol <1.8/>3.0 mmol/L. Age, BMI, and HbA1c levels were balanced between the LDL-cholesterol subgroups, but those in the lowest versus highest group, had more coronary artery disease (83.0% vs 59.9%) and statin treatment (88.2% vs 50.9%). Empagliflozin consistently reduced all outcomes across LDL-cholesterol categories (all interaction p-values > 0.05).Conclusion:The beneficial cardiovascular effects of empagliflozin was consistent across higher and lower LDL-cholesterol levels at baseline.
Highlights
Empagliflozin is a potent and selective sodium glucose cotransporter 2 (SGLT2) inhibitor used for the treatment of type 2 diabetes (T2D)
Our analysis shows that the modulating beneficial effects of empagliflozin on CV outcomes did not differ between the categories of baseline low-density lipoprotein (LDL)-C levels
Consistent with overall effects, protective effects is likely be expected in those with low LDL-C levels, which many patients accomplish with use of high-dose statins, combined, if needed, with ezetimibe and/or inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9),[5] the latter was not studied in EMPA-REG OUTCOME
Summary
Empagliflozin is a potent and selective sodium glucose cotransporter 2 (SGLT2) inhibitor used for the treatment of type 2 diabetes (T2D). In the EMPA-REG OUTCOME trial, in patients with T2D and high CV risk, empagliflozin added to standard of care significantly reduced the risk of 3-point major adverse CV events (3P-MACE) by 14%, CV death by 38%, and hospitalization for heart failure (HHF) by 35%, compared with placebo.[1] As there are numerous clinical and genetic studies that demonstrate a cause and effect relationship between LDL-C levels and the risk of CV events,[2,3] the objective of this post-hoc analysis was to determine if CV outcomes with empagliflozin compared with placebo was impacted by baseline LDL-C levels in the EMPA-REG OUTCOME trial.
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