Efficacy of dapagliflozin in the treatment of HFrEF with obstructive sleep apnea syndrome (DAHOS study): study protocol for a multicentric, prospective, randomized controlled clinical trial

Abstract

Background Heart failure with reduced ejection fraction (HFrEF) is associated with sleep dyspnea (SDB), which plays an adverse role in the pathophysiology of the condition. SDB management in HFrEF, however, remains controversial. HFrEF’s medical management has recently made significant progress with the discovery of new therapeutic avenues, namely sodia-glucose cotransporter-2 (SGLT-2) inhibitors, and better treatment of co-morbidities. Dapagliflozin, one of the SGLT-2 inhibitors, is a good candidate for correcting SDB of HFrEF patients because their known mechanisms of action are likely to counteract the pathophysiology of SDB in HFrEF. Methods/design The trial is a 3-month, multicentric, prospective, randomized controlled clinical study. Patients (i.e., adults with left ventricular ejection fraction ≤ 40%, Apnoea–Hypopnoea Index ≥ 15) will be randomized to receive optimized heart failure therapy plus a standard dose of dapagliflozin, while the control group will receive only optimized heart failure therapy. Patients will be evaluated before and after 3 months (nocturnal ventilatory polygraphy, echocardiography, laboratory testing, and quality-of-life and SDB questionnaires). The primary outcome is the change in the Apnoea–Hypopnoea Index, before and after 3 months of treatment. Trial registration www.chictr.org.cn, ChiCTR2100049834. Registered 10 August 2021.

Kidneys in heart failure: Impact of flozins

“…SGLT2i, though well-established in the treatment of diabetes, CVD, and CKD (and any combination of these diseases) and included in many national and international guidelines are still the subject of clinical research -new trials are planned or ongoing to make indications to SGLT2i even broader. The key directions of such research include use of SGLT2i in heart transplant and kidney transplant recipients, acute heart failure, coronary artery disease and acute myocardial infarction, or treatment of diseases contributing to increased risk of CVD and CKD, such as sleep apnea syndrome [91][92][93][94][95][96]. Randomized trials are also planned or ongoing that assess the efficacy of SGLT2i combined with another drug with confirmed cardiovascular and renal benefits in T2DM patients, namely finerenone, a onein-the-class non-steroidal mineral corticosteroid receptor antagonist [97].…”

Association between Obstructive Sleep Apnea and Heart Failure in Adults—A Systematic Review

“…The primary endpoint of the main study is the decreasing value of AHI. The secondary outcomes of the study include assessing the proportion of patients experiencing a 20% and 50% decrease in the AHI before and after dapagliflozin treatment, evaluating changes in Epworth Sleepiness Scale (ESS) scores, examining echocardiographic measures of structure and function (ejection fractions, left ventricular diameters, atrial surface, diastolic function, and filling pressures) pre-and post-dapagliflozin, analyzing serum BNP and pro-BNP concentrations before and after dapagliflozin, measuring laboratory parameters such as creatinine, potassium, sodium, hemoglobin, alanine, and aspartate transaminase levels, assessing the quality of life using the Minnesota Living with Heart Failure Questionnaire and EQ-5D-3L Questionnaire, and evaluating levels of inflammatory and oxidative stress factors (IL-6, CRP) before and after dapagliflozin [47].…”