Continuous Positive Airway Pressure (CPAP) in Patients With Acute Coronary Syndrome and Obstructive Sleep Apnea (OSA) (ISAACC)

Sociedad Española de Neumología y Cirugía Torácica

Status: Completed

Conditions: Acute Coronary Syndrome; Obstructive Sleep Apnea

Treatments: Other: Standard care; Device: continuous positive airway pressure

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01335087

PI10/02763

Details and patient eligibility

About

OSA may be a modifiable risk factor for cardiovascular disease due to its association with hypertension, stroke, heart attack and sudden death. The standard therapy for symptomatic OSA is continuous positive airway pressure (CPAP). CPAP has been shown to effectively reduce snoring, obstructive episodes and daytime sleepiness and to modestly reduce blood pressure and other risk factors for cardiovascular disease. The overall aim of ISAACC is to determine if CPAP can reduce the risk of heart attack, stroke or heart failure for people with OSA admitted in a hospital for an acute coronary syndrome.

Overall objective:

To assess the impact of obstructive sleep apnea (OSA) and its treatment on the clinical evolution of patients with acute coronary syndrome (ACS).

Primary objectives:

1. To determine if continuous positive airway pressure (CPAP) treatment will reduce the rate of cardiovascular events (cardiovascular (CV) death, non-fatal events (acute myocardial infarction (AMI), non-fatal stroke, hospital admission for heart failure, and new hospitalizations) for unstable angina or transient ischaemic attack (TIA)) in patients with ACS and co-occurring sleep apnea.

Secondary objectives:

1. Determine the prevalence of OSA in patients who have suffered an episode of ACS.

2. Other secondary objectives will include the effects of CPAP on:

   • To evaluate a composite of CV death, myocardial infarction (MI) and ischaemic stroke.
   • Components of primary composite endpoints
   • Re-vascularization procedures
   • To evaluate all-cause death
   • To evaluate new onset, ECG-confirmed atrial fibrillation or other arrhythmias
   • To evaluate newly diagnosed diabetes mellitus, according to standard definitions
   • To evaluate OSA symptoms (Epworth Sleepiness Scale (ESS))
   • To evaluate quality of life in patients with ACS (Test EuroQol (EQ-5D).

3. To establish the relationship between the severity and phenotype of patients with OSA and clinical outcomes of ACS.

4. To establish the relationship between CPAP compliance and CV events incidence.

5. To identify biological risk markers that allow us to establish the most important mechanisms involved in cardiovascular complications in these patients.

6. To conduct a cost-effectiveness analysis of the diagnosis and CPAP treatment of patients with ACS who have obstructive sleep apnea.

Full description

Methods:

Study design: multi-centre, open label, parallel, prospective, randomised, controlled trial.

Patients: We will include consecutive patients with an ACS diagnosis evaluated in participating Coronary Care Unit.

Study sites: IRB Lleida (Lleida), Hospital Son Dureta (Palma de Mallorca), Hospital Clínic (Barcelona), Hospital Germans Tries i Pujol (Barcelona), Hospital de Bellvitge (Barcelona), Hospital Sant Pau (Barcelona), Hospital Txagorritxu (Vitoria), Hospital de Cruces (Bilbao), Hospital San Pedro de Alcántara (Cáceres), Hospital Parc Taulí (Barcelona) and Hospital de Guadalajara (Guadalajara), Hospital de Vallecas (Madrid), Hospital de Yagüe (Burgos), Hospital de Requena (Valencia), Hospital San Juan, (Alicante), Hospital Central de Asturias (Oviedo).

Duration of the study: 3 years. Methodology: During a hospital stay we will assess the degree of daytime sleepiness (Epworth Scale) in patients treated at the Coronary Care Unit with a diagnosis of ACS. The results of this evaluation will define the inclusion of the patient in the study.

Patients with and ESS score ≤ 10 will be included in the study and will undergo a cardio-respiratory polygraphy. Patients with an AHI ≥ 15 h-1 will be randomized to CPAP treatment or conservative. Patients with and AHÍ < 15 h-1 will be followed as standard management according to cardiovascular protocols and will be evaluated as a reference group. Therefore, the study will have three groups, with a total of 1,864 patients, as follows: patients with an AHI ≥ 15 h-1 will be randomized to CPAP treatment (Group 1) (n=632) or conservative treatment (Group 2) (n=632). Patients with an AHI < 15 h-1 that will be followed as a reference group (Group 3) (n=600).

Patients with an ESS score higher than 10 will be excluded of the study and referred to the sleep unit of each participating center for evaluation.

Patients included in the study will be monitored and followed for a minimum of one year and a maximum of three years. Patients will be examined at the time of inclusion (T0), after one month (T1), three months (T2), six months (T3), 12 months (T4) and every six months thereafter, if applicable, during the follow-up period. Evaluations will include; i)new episodes of ACS, stroke, TIA, heart failure, hospitalization for cardiovascular causes and cardiovascular mortality, ii) biological risk markers involved in cardiovascular complications, iii) an evaluation of the cost-effectiveness of diagnosis and CPAP treatment in patients with ACS who have obstructive sleep apnea.

Enrollment: 1,864 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Men and women over 18 years old.
2. Patients admitted for documented symptoms of ACS with or without T segment elevation and have an hospital stay between 24h and 72 h in the moment to perform polygraphy .
3. Patients with and Epworth Sleep Scale score ≤ 10 (patients without excessive daytime sleepiness).
4. Written informed consent signed.

Exclusion criteria

1. Previous CPAP treatment for OSA diagnosis
2. Psycho-physical inability to complete questionnaires.
3. Presence of any previously diagnosed sleep disorders: narcolepsy, insomnia, chronic sleep deprivation, regular use of hypnotic or sedative medications and restless leg syndrome
4. Patients with > 50% of central apneas or the presence of Cheyne-Stokes Respiration (CSResp)
5. Patients with chronic diseases: neoplasia, renal failure (GFR<30 ml/min), severe chronic obstructive pulmonary disease, chronic depression and other very limiting chronic diseases.
6. A medical history that may interfere with the study objectives or, in the opinion of the investigator, compromise the conclusions.
7. Any medical factor, social or geographical, that may jeopardize patient compliance.(e.g., alcohol consumption (more 80 gr/day in men and more than 60 gr / day in women), no fixed address, disorientation, or a history of non-compliance).
8. Any process, cardiovascular or otherwise, that limits life expectancy to less than one year.
9. Patients in cardiogenic shock who have poor expectations for short-term outcomes.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

1,864 participants in 3 patient groups

Lifestyle

Active Comparator group

Description:

Standard care for OSA: lifestyle, and sleep hygiene counselling

Treatment:

Other: Standard care

Continuous positive airway pressure CPAP

Experimental group

Description:

CPAP treatment every night plus standard care for OSA: lifestyle, and sleep hygiene counselling

Treatment:

Device: continuous positive airway pressure

Other: Standard care

Reference

No Intervention group

Description:

This group will be followed according to cardiovascular protocols and will be evaluated as a reference group.