Effects of Empagliflozin on Oxidative Stress in Patients with Obstructive Sleep Apnea and Heart Failure: A Randomized Clinical Trial

Obstructive sleep apnea (OSA) and heart failure (HF) share pathways involving intermittent hypoxia and oxidative stress. This randomized clinical trial with blinded endpoint assessment evaluated systemic oxidative balance during sequential treatment with empagliflozin and continuous positive airway pressure (CPAP). Seventy adults with HF and predominantly obstructive OSA were randomized to empagliflozin 10 mg daily plus background HF therapy (n = 37) or background therapy alone (n = 33). Assessments were performed at baseline, month 3, and month 6; CPAP was initiated in both groups after month 3. The primary endpoint was the between-group difference in AHI change from baseline to month 3, estimated using a baseline-adjusted linear mixed-effects model. TOS, TAS, and OSI were exploratory outcomes. Median AHI (IQR) in the study and control groups was 58.9 (28.5–70.3) and 55.0 (29.9–67.8) at baseline, and 44.2 (22.4–59.3) and 52.2 (30.8–70.2) at month 3, respectively. The baseline-adjusted between-group difference in AHI change from baseline to month 3 was −11.04 (95% CI −16.72 to −5.35; p < 0.001). The exploratory mixed-effects models showed lower TOS and OSI and higher TAS in the study group at both follow-up visits (all p < 0.001). Empagliflozin initiation was associated with early reductions in AHI and improvements in exploratory markers of systemic oxidative balance before CPAP initiation. Although the shared CPAP phase did not allow separation of drug and CPAP effects, these findings support further investigation of the respiratory and redox effects of empagliflozin in patients with coexisting HF and OSA.