Empagliflozin Reduces Cardiovascular Outcomes Despite Obstructive Sleep Apnea

Henry Yaggi, MD

Sodium glucose co-transporter (SGLT)-2 inhibitors could help reduce some of the negative cardiovascular outcomes for patients with type 2 diabetes and obstructive sleep apnea (OSA), according to data planned for presentation at the American Thoracic Society (ATS) 2020 International Conference.

A team, led by Henry Yaggi, MD, Yale University, examined incidence rates of cardiovascular events, hospitalizations for heart failure, and mortality outcomes in patients with or without obstructed sleep apnea at baseline treated with empagliflozin.

Obstructive sleep apnea and type 2 diabetes frequently occur in obese individuals, where both disorders are liked with metabolic disturbances that increase the risk of cardiovascular disease.

In the randomized placebo-controlled outcome study, dubbed the EMPA-REG OUTCOME trial, the investigators examined 7020 patients from 42 countries with type 2 diabetes and cardiovascular disease.

The investigators found empagliflozin reduced HbA1c, systolic blood pressure, waist circumference, and weight, while also reducing the risk of three-point major adverse cardiovascular events (3P-MACE) by 14% and cardiovascular death by 38%. The treatment also resulted in a 35% reduction in hospitalization for heart failure.

The patients included in the trial had a bA1c 7.0-9.0% for drug-naïve patients and 7.0-10.0% for those on stable glucose-lowering therapy, established CVD, and estimated glomerular filtration rate >30 mL/min/1.73 m².

Each patient was randomized to receive either empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily, in addition to standard of care.

The investigators independently adjudicated all cardiovascular outcomes, with events pooled for the 10 and 25 mg doses of the SGLT-2 inhibitor.

In a post-hoc analysis, the investigators assessed obstructive sleep apnea based on investigator reports using MedDRA 18.0 and incidence rates for outcomes reported by adjusted event-rates per 100 patient-years.

The team also used Cox regression models with multivariable adjustments to analyze the effects on outcomes.

In the 7020 patient population, 391 had OSA (5.6% [placebo 5.4%; pooled empagliflozin doses 5.7%]. In a comparison to patients without obstructive sleep apnea at baseline, individuals with the disease were more frequently male (82.9% vs 70.8%), living in North-America (63.2% vs 17.3%), and had more obesity (BMI ≥ 35 kg/m²: 55.2% vs 18.2%) and more coronary artery disease (88.0 vs 74.9%).

Over a median of 3.1 years, patients with OSA at baseline compared to those without OSA in the placebo group, experienced a 1.3-2.0 fold higher event rates for 3P-MACE (OSA vs no OSA: 6.49 vs 4.27/100-patient-year), cardiovascular death (2.57 vs 1.99), hospitalization for heart failure (2.71 vs 1.38), and all-cause mortality (4.29 vs 2.78).

However, the investigators found empagliflozin improved all of these measures regardless of the presence of obstructive sleep apnea at baseline (P <0.05).

“In this post-hoc exploratory analysis, patients with OSA had higher frequency of events for 3P-MACE, HHF and mortality,” the authors wrote. “The cardio-protective effects of empagliflozin was consistent in those with and without OSA at baseline.”

The study, “Obstructive Sleep Apnea and Cardiovascular, Heart Failure and Mortality Outcomes with Empagliflozin Versus Placebo in the EMPA-REG Outcome®Trial,” was published online by the ATS International Conference.