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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SACUBITRIL - VALSARTAN | Experimental | SACUBITRIL - VALSARTAN (formerly LCZ696, 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SACUBITRIL - VALSARTAN (formerly LCZ696, ENTRESTO®) | Drug | SACUBITRIL - VALSARTAN (formerly LCZ696, 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Apnea-Hypopnea Index as compared to baseline | Changes in AHI as compared to baseline Measure of the apnea hypopnea index by a polygraphy performed before and after 3 months of treatment. The 2012 American Academy of Sleep Medicine recommendations are utilized in order to characterized apnea and hypopnea events, the central or obstructive or mixed phenotype | 0 month to 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Subject Global Assessment | 0 month to 3 months | |
| NYHA Functional Class | 0 month to 3 months | |
| Heart Rhythm |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Arnaud BOURDIN, MD,PhD | University Hospital, Montpellier | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Bordeaux | Bordeaux | Pessac | 33604 | France | ||
| Pôle médical spécialisé MSP |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29469206 | Background | Jaffuel D, Molinari N, Berdague P, Pathak A, Galinier M, Dupuis M, Ricci JE, Mallet JP, Bourdin A, Roubille F. Impact of sacubitril-valsartan combination in patients with chronic heart failure and sleep apnoea syndrome: the ENTRESTO-SAS study design. ESC Heart Fail. 2018 Jun;5(3):222-230. doi: 10.1002/ehf2.12270. Epub 2018 Feb 22. | |
| 34102018 |
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| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
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| ID | Term |
|---|---|
| C549068 | sacubitril and valsartan sodium hydrate drug combination |
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|
physiological parameter |
| 0 month to 3 months |
| Systolic and diastolic Blood Pressure | physiological parameter | 0 month to 3 months |
| Renal function as compared to baseline (Estimated GFR (eGFR) will be calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula | CKD-EPI formula | 0 month to 3 months |
| BNP (B-type Natriuretic Peptide) rates | Biological parameter | 0 month to 3 months |
| Subject medications | 0 month to 3 months |
| Quality of life as measured by Minnesota Living with Heart Failure Questionary | Questionaries | 0 month to 3 months |
| Quality of life as measured by EQ-5D-3L Questionary | Questionaries | 0 month to 3 months |
| Epworth Sleepiness Scale | Questionary | 0 month to 3 months |
| Pichot Fatigue Scale | Questionary | 0 month to 3 months |
| Type of device used in group 2 patients | CPAP or ASV device CPAP/ASV : continuous positive airway pressure / adaptive servo ventilation | 0 month to 3 months |
| CPAP/ASV compliance in group 2 patients | CPAP/ASV compliance. Unit : number of hour per day using CPAP/ASV device | 0 month to 3 months |
| Historical of CPAP/ASV compliance in group 2 patients | CPAP/ASV compliance. Unit : number of day with ≥3 hours in the past 6 months | 0 month to 3 months |
| Settings of CPAP/ASV device used in group 2 patients | Settings of device | 0 month to 3 months |
| Type of mask used in group 2 patients | Type of mask | 0 month to 3 months |
| Historical use of mask in group 2 patients | Historical use of mask | 0 month to 3 months |
| Changes in AHI compared to Baseline in group 2 patients | Changes in AHI compared to Baseline | 0 month to 3 months |
| Béziers |
| 34500 |
| France |
| CHU Béziers | Béziers | 34525 | France |
| Centre Hospitalier Universitaire de Montpellier | Montpellier | 34295 | France |
| CHU Nimes | Nîmes | 30029 | France |
| CHU Toulouse | Toulouse | 31059 | France |
| Jaffuel D, Nogue E, Berdague P, Galinier M, Fournier P, Dupuis M, Georger F, Cadars MP, Ricci JE, Plouvier N, Picard F, Puel V, Mallet JP, Suehs CM, Molinari N, Bourdin A, Roubille F. Sacubitril-valsartan initiation in chronic heart failure patients impacts sleep apnea: the ENTRESTO-SAS study. ESC Heart Fail. 2021 Aug;8(4):2513-2526. doi: 10.1002/ehf2.13455. Epub 2021 Jun 8. |
| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |