Sleep Apnea CardioVascular Endpoints Study - SAVE

continuous positive airway pressure (CPAP) device A China-Australia collaborative, multi-centre program of research to establish the benefits of treatment of obstructive sleep apnea (OSA) on cardiovascular outcomes.

The SAVE website

Background

OSA is a very common condition characterised by varying degrees of repetitive episodes of upper airway obstruction (apnea) or narrowing (hypopnea) during sleep, loud snoring, and daytime sleepiness. 10% of middle-aged men and 4% of middle-aged women have significant OSA (ie >15 obstructive events per hour of sleep).

Increasing age, obesity and male gender are the best recognised risk factors for OSA. OSA reduces quality of life and increases road accident rates. Currently most cases go undetected.

Continuous Positive Airway Pressure (CPAP) is considered standard treatment of symptomatic OSA in most developed countries.

CPAP treatment reduces the symptoms and improves the quality of life in OSA patients, and is generally well-tolerated.

OSA may increase risk of cardiovascular disease

There is now wide-ranging evidence that OSA may be a risk factor in the development of cardiovascular disease. Large population studies have demonstrated associations with:

  • increased blood pressure
  • stroke
  • acute coronary syndromes
  • heart failure
  • sudden death

Cardiovascular disease is the leading cause of global disease burden and is predicted to increase, particularly in low-middle income nations, due to ageing and lifestyle changes. Given the above associations, OSA is a potential important modifiable risk factor.

CPAP as risk modifier

CPAP is well-established as an effective treatment to improve the daytime sleepiness associated with OSA, as well as improving other markers of the disease (nocturnal oxygen saturation, sleep fragmentation, quality of life measures). There is limited evidence suggesting CPAP can also improve cardiovascular risk factors; however previous studies have not definitively demonstrated that CPAP treatment reduces cardiovascular mortality and morbidity.

Since OSA is highly prevalent and amenable to cost-effective treatments, a major advancement in health care could be made if it can be established reliably that OSA is a significant cause of cardiovascular events, and premature death and disability. It is anticipated that screening for OSA would then become part of routine clinical care in cardiovascular medicine, and integrated within public health campaigns aimed at reducing cardiovascular morbidity and mortality.

OSA in the Chinese setting

There is currently relatively little community awareness of OSA in China compared to developed countries. Additionally access to treatment is severely restricted by cost - CPAP is currently beyond the means of nearly all sufferers of OSA. Thus the vast majority of cases in China currently go undetected and untreated.

Aims

The SAVE Study is to be conducted in 3 separate phases.

SAVE Validation Study:

  • Establish the frequency of OSA in a high cardiovascular risk community-based population.
  • Test the predictive value of two simple OSA screening devices (nasal airflow and pulse oximetry); if successful these devices will be used in subsequent phases of SAVE.

SAVE Trial (main):

  • Determine the effectiveness of nasal CPAP in reducing the incidence of the primary cardiovascular endpoints of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for heart failure.

SAVE I Substudy

  • Conduct a randomised, controlled evaluation of CPAP against usual care in 600 high cardiovascular risk subjects with OSA for the endpoints of blood pressure, lipids, glucose control, and inflammatory markers at 6 months.

Methods

The SAVE Validation Study will recruit high-cardiovascular risk patients from the Luwan District of Shanghai, who have previously been identified from a community survey of nearly 200,000 residents. Approximately 200 high- and low-OSA risk participants will undergo overnight polysomnography and simultaneous single-parameter screening tests (pulse oximetry and nasal flow), to determine the diagnostic predictive value of these tests compared to the gold-standard polysomnography.

SAVE Main Trial (scheduled to begin late 2008) will enrol over 6000 participants for a long-term, randomised, controlled trial of CPAP versus usual care in a high-cardiovascular risk population. The primary endpoints of this main phase would be the rate of cardiovascular events (i.e. mycordial infarction, stroke, re-vascularisation procedures) over several years.

Study Status

The SAVE Validation Study began recruiting patients in mid-April 2007 with an expected recruitment period of 3-4 months, during which time over 200 sleep studies will be performed. Data analysis will commence in late July-early August 2007. The SAVE Trial will commence in mid to late 2008.

Steering Committee

Funding