sacubitril-valsartan and heart failure patients : the entresto-sas study

Conditions: Chronic Heart Failure; Sleep Apnea Syndrome

Summary: chronic heart failure (chf) is a frequent pathology burdened with mortality and significant morbidity. sleep apnea syndrome (sas) is frequently associated with chf in 20% to 75% of cases. treatment of sas is however inconsistently associated with a decline in the morbidity and mortality. to date, the chf medical treatments have been reported to be inconsistently efficient in the treatment of sas. sacubitril-valsartan (entresto®) is a new treatment of chf recently indicated class i, level b in the recent european society of cardiology (esc) guidelines 2016 on chf. paradigm-hf trial demonstrated that morbidity and mortality can be improved with sacubitril-valsartan. in comparison to enalapril, it reduced the occurrence of cardiovascular death or hospitalisation for chf by 20% with a 16% reduction in all-cause mortality. the purpose of the research is the evaluation of sacubitril-valsartan combination in chf patients presenting sleep apnea syndrome. a three months real life observational trial is performed. a measure of the apnea hypopnea index is realised before and after 3 months of sacubitril-valsartan treatment. a concomitant evaluation of cardiological and quality of life parameters is realized.

the chronic heart failure (chf) is a frequent pathology burdened with mortality and significant morbidity. chronic hf provides almost 2% of health expenditure in developed countries, it is the largest expenditure item in the usa (34.8 billion dollars). in most developed countries, including france, mortality 1 year after diagnosis of chronic hf is 40%, it is 50% at 2 years, and over 70% at 4.5 years. sleep apnea syndrome (sas) is frequently associated with hf in 20% to 75% of cases. the presence of an apnea syndrome is associated with a greater morbidity and mortality. treatment of sas is however inconsistently associated with a decline in the morbidity and mortality. to date, the chf medical treatments have been reported to be inconsistently efficient in the treatment of sas : 6 studies corresponding to a total of 67 patients and 5 types of molecules reported an incomplete effect on the central component of the apnea hypopnea index (ahi) for these patients. sacubitril - valsartan (entresto®) is a new treatment of hf recently indicated class i, level b in the recent esc guidelines 2016 on hf. it combines inhibitory prodrug neprilysin and valsartan. after initial failures with neprilysin inhibition alone or dual neprilysin-angiotensin converting enzyme (ace) inhibition, the paradigm-hf trial demonstrated that morbidity and mortality can be improved with the sacubitril - valsartan combination (formerly lcz696). in comparison to the ace inhibitor enalapril, sacubitril/valsartan reduced the occurrence of the primary end point (cardiovascular death or hospitalisation for hf) by 20% with a 16% reduction in all-cause mortality. these findings suggest that sacubitril/valsartan should replace an ace inhibitor or angiotensin receptor blocker as the foundation of treatment of symptomatic patients (nyha ii-iv) with hf and a reduced ejection fraction. the purpose of the research is the evaluation of sacubitril-valsartan in chf patients presenting sleep apnea syndrome. we speculate that synchronously of a beneficial effect on heart failure, the sacubitril-valsartan combination could improve an associated sas and in particular the central component of the ahi index. after an exhaustive initial pre-therapeutic evaluation, the sacubitril-valsartan combination treatment is initiated for 3 months. the pre-therapeutic evaluation includes cardiological and biological exams, quality of life questionaries and nocturnal ventilatory polygraphy. considering the results of the polygraphy, three groups of patients are identified: * group 1 patients, characterized by a central ahi ≥5 / h and an obstructive ahi \<15 / h, * group 2 patients, characterized by an obstructive ahi ≥15 / h whatever is the central component. in this group of patient, a ventilator treatment with constant positive airway pressure or auto-servoventilation is started. * group 3 patients, characterized by a central ahi \< 5 / h and an obstructive ahi \<15 / h. after three months of treatment, the final evaluation includes cardiological and biological exams, quality of life questionaries for all the patient included in the trial. a nocturnal polygraphy is performed only in group 1 and 2 patients. for group 2 patients treated with a device, the observance to the device, the residual ahi device and the pressure device is measured.

Eligibility criteria:
inclusion criteria: * age is greater than or equal to 18 years * patient with chronic heart failure (lvef ≤ 45%). * written informed consent exclusion criteria: * renal insufficiency (gf\<30 milliliters/min) * pregnancy * allergy to one compound * personal history of angiooedema * hemodynamical instability * severe hepatopathy * current and not treated hyperkaliemia * prognosis \< 6months * current cpap or asv treatment for sleep apnea syndrome

Keywords: chronic heart failure sleep apnea syndrome continuous positive airways pressure sacubitril - valsartan