Implications of the Sleep Apnoea Cardiovascular Endpoints (SAVE) Study for decision-making for people with obstructive sleep apnoea and cardiac disease about use of CPAP machines to prevent further cardiac disease
A commentary by Professor Alun Jackson and Michael Le Grande
There has been a lot of media attention on the value of using continuous positive airway pressure (CPAP) machines for people with established cardiac disease since the SAVE study results were recently published in the New England Journal of Medicine. Much of the media discussion has left people with the impression that if you want to prevent cardiac disease, then use of a CPAP machine is not really going to do the job.
It would be unfortunate if this belief resulted in people choosing not to address their cardiovascular disease (CVD) risk by using a CPAP device to do something about their obstructive sleep apnoea (OSA).
Why was this trial important?
Obstructive sleep apnea is a common disorder, estimated to occur in 9% of women and 25% of men in Australia, and has been associated with an increased risk of cardiovascular disease. CPAP is frequently prescribed in patients with obstructive sleep apnoea and is effective in reversing low levels of oxygen in arterial blood (hypoxaemia) and upper airway obstruction. Meta-analyses of randomized trials have shown that CPAP therapy elicits significant reductions in systemic arterial pressure, with greater effect the more the CPAP machine is used. Observational studies have shown significantly fewer cardiovascular events in patients’ adherent to CPAP therapy than in those who are not, but there was a need for large trials such as the SAVE study.
What did the SAVE study do?
This international study, led by Australian sleep specialists, found that machines designed to help people with sleep apnoea do not reduce the risk of heart attack or stroke, in people with established heart disease, but that it significantly improved quality of life.
The Sleep Apnoea Cardiovascular Endpoints (SAVE) study of more than 2,700 sleep apnoea sufferers with cardiovascular disease monitored sleep apnoea patients with a pre-existing cardiovascular disease over four years in 89 hospitals in 7 countries around the world, including Australia. Researchers were looking at whether a CPAP machine would prevent major cardiovascular events, including heart attack and stroke. 1,341 usual care and 1,346 CPAP patients included in the final analysis were followed for an average of 3.7 years. The primary outcome was measured as death from any CV cause, myocardial infarction or stroke, and hospitalisation for heart failure, acute coronary syndrome, or transient ischemic attack. Results showed no difference between groups on the primary outcome.
Importantly though, CPAP did improve the wellbeing of participants, defined by symptoms of daytime sleepiness, health-related quality of life, mood – particularly depressive symptoms, and attendance at work.
What are some of the issues with the SAVE study?
There are a number of issues with the SAVE study that should encourage caution in using the findings in decision-making about using CPAP as a preventive measure in cardiac disease:
The population studied: CPAP may have limited effect in patients with well-established cardiovascular disease and that using CPAP for 3.3 hours/night of CPAP in MILD, minimally symptomatic, non-sleepy patients fails to improve cardiovascular risk. This is not surprising.
Time that CPAP was used: Patients did not use CPAP for long enough each night to derive cardiovascular benefits. The mean duration of CPAP adherence was only 3.3 hours per night, which is probably less than half the time the patient was asleep. In a matched analysis in the SAVE study, those patients who used CPAP for more than 4 hours per night actually showed a trend toward a slightly lower risk of a primary end-point event in the CPAP group compared to usual care patients. At least 4 hours use is now the recommended dose but there is convincing evidence that at least 6 hours is required to decrease the incidence of cardiovascular events including hypertension.
Timing of CPAP use: Most of the patients in the SAVE study used CPAP in the beginning of the night. This is less effective than using it later in the night, when more serious instances of low oxygen uptake are more likely. Further, CPAP is more effective in lowering hypertension if it is used throughout the night, rather than just at the beginning.
Generalising the results: The results have limited application to the Australian context as the study population was two-thirds Asian with an average Body Mass Index (BMI) of 28, that is, non-obese, which is not typical of the Australian OSA population.
Type of machine used in the study: The CPAP devices themselves were limited and possibly obsolete by 2016 standards. For example, more recently developed auto-titrating positive airway pressure devices of various kinds each with their optimised algorithms were not assessed. Devices listed were current in 2008-2010 – many advances in last 5 years may have improved effectiveness and compliance.
Other benefits of CPAP with this population: The SAVE study demonstrated that CPAP usage had a significant beneficial effect on quality of life, mood, daytime sleepiness, and work productivity. These effects may have a beneficial impact on people’s ability to attend, and benefit from, cardiac rehabilitation. Additionally, there may be more beneficial longer term outcomes, which may be evident past the three year follow up period of the SAVE study.
What do the results mean for practice?
For symptomatic patients with obstructive sleep apnea, a trial of CPAP should be offered. It would also be prudent to offer CPAP to patients with obstructive sleep apnea and severe hypoxemia during sleep regardless of symptoms –the type of patients excluded from the SAVE trial.
On the basis of the results from the SAVE trial, prescribing CPAP for the sole purpose of reducing future cardiovascular events in asymptomatic patients with obstructive sleep apnea and established cardiovascular disease cannot be recommended. However, it is likely to be beneficial in improving quality of life, mood, daytime sleepiness, and work productivity, and should therefore be recommended to achieve these purposes.
Patients attending cardiac rehabilitation should be screened for OSA and recommended for full assessment for OSA and possible prescribed use of CPAP or other devices, such as mandibular advancement splints, for those who find adherence to CPAP difficult.