Summary: A post-hoc analysis of three major clinical trials found that CPAP therapy lowers the risk of cardiovascular events only in patients with high-risk OSA—defined by high hypoxic burden or heart rate response. For patients with low-risk OSA, particularly those without excessive daytime sleepiness, CPAP may actually increase cardiovascular risk. The findings underscore the need for a personalized treatment approach and challenge the one-size-fits-all model for CPAP use in OSA patients with heart disease.
Key takeaways:
- CPAP reduced cardiovascular events by ~17% in patients with high-risk OSA.
- In patients with low-risk OSA, CPAP increased cardiovascular events by ~22%, especially in non-sleepy individuals.
- CPAP may pose harm in low-risk OSA by causing lung stretch or sleep disruption.
- A new clinical trial is focused on people with high-risk OSA.
CPAP lowers the risk of serious cardiovascular events in some patients with obstructive sleep apnea (OSA) but not others, according to a post-hoc analysis of three previously published trials. The findings, published in the European Heart Journal today, suggest that a more personalized approach for treating patients is needed—one that focuses on CPAP treatment for those who stand to gain the most, while exercising caution for those who may not benefit and could even be harmed.
“Through our study, we found a subgroup of patients who experience cardiovascular benefits from CPAP use,” says first author Ali Azarbarzin, PhD, of the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital, in a release. “This is the first step in making better therapeutic recommendations for patients with obstructive sleep apnea in the future to reduce their risk of heart attack, stroke, and death.”
Re-Analyzing Three OSA Trials
“We know that OSA is linked to cardiovascular disease, but clinical studies of treating OSA with CPAP have not shown a long-term cardiovascular benefit. This creates uncertainty about whether all people with OSA should be treated,” says Azarbarzin, a founding member of the Mass General Brigham healthcare system.
The research team analyzed data from three previous trials of patients with OSA and cardiovascular disease: RICCADSA, ISAACC, and SAVE. In this way, the post-hoc study included 3,549 total patients with a median age of 61 years—half using CPAP, half not. They tracked the patients for three years on average, looking at the incidence of cardiovascular mortality, stroke, and heart attack.
Overall, 16.6% of patients using CPAPs had major cardiac events, compared to 16.3% of patients not using CPAPs—not a statistically significant difference.
High-Risk OSA Versus Low-Risk OSA
However statistically significant difference did appear when these patients were further split into subgroups: those with sleep study markers of high- and low-risk OSA.
- High-risk OSA: characterized by large drops in blood oxygen levels (hypoxemia) OR heart rate spikes during breathing disruptions.
- Low-risk OSA: patients with OSA but without either of these two markers.
The re-analysis revealed that, in patients with high-risk OSA, CPAP lowered the risk of heart attack, stroke, and death from cardiovascular disease by around 17%.
This was 31% better than the effect of treatment in those with low-risk OSA, for whom CPAP may even increase the risk of serious cardiovascular events by around 22%.
When the high- and low-risk groups were further sorted based on their daytime symptoms—asymptomatic non-sleepy or symptomatic sleepy—those trends were even stronger. Non-sleepy patients with high-risk markers experienced 24% fewer cardiovascular events, while non-sleepy patients with low-risk markers experienced 30% more cardiovascular events.
Clinical Implications
“For people with high-risk OSA, CPAP likely helps by preventing low oxygen levels and calming the overactive sympathetic nervous system during sleep. Both of these are linked to cardiovascular disease,” Azarbarzin says. “But in people without these high-risk markers, who are already at very low cardiovascular risk, CPAP seems to have downsides. While we don’t really know why, one possibility is that the pressure used in CPAP may stretch the lungs in a way that puts stress on the cardiovascular system. Another is that CPAP could disturb sleep for some people, and sleep disruption itself is a risk factor for cardiovascular problems. More research is needed to understand these mechanisms.
“Our findings suggest a more personalised approach to treating OSA. Instead of treating everyone the same, we should consider whether someone has high-risk features. These are the people who seem most likely to benefit from CPAP. For clinicians and policy makers, this means we may need to rethink current guidelines for treating non-sleepy patients and consider focusing treatment for cardiovascular risk reduction on those who stand to gain the most. We also need to be cautious about using CPAP in people who don’t have high-risk markers, as they may not benefit and could even be harmed.
“CPAP-related harm was seen only in non-sleepy patients with existing heart disease, according to the design of the trials analysed in this study. Whether this applies to other patients remains unknown and needs further research.”
Additional Perspective
In an accompanying editorial, Andrea Natale, MD, from Texas Cardiac Arrhythmia Institute, said: “OSA has been reported to increase the risk of heart failure by 140%, the risk of stroke by 60%, and the risk of coronary heart disease by 30%.
“Three major randomised trials (RCTs), ISAACC, RICCADSA, and SAVE, between 2016 and 2020, published their assessment on the effects of CPAP on the long-term adverse cardiovascular outcome risk in OSA patients with pre-existing cardiovascular comorbidities.…each of these three RCTs demonstrated the failure of CPAP therapy in reducing the cardiovascular risk in minimally sleepy or non-sleepy patients with moderate to severe OSA.
“The current meta-analysis by Azarbarzin et al., published in this issue of the European Heart Journal, examined the role of CPAP in reducing CV risk in patients with vs. without high-risk OSA, defined as the presence of either a high pulse rate response or a high hypoxic burden, by pooling individual patient data from the three RCTs mentioned above.
“The current study reported two novel findings that are worth mentioning. First, the authors demonstrated a harmful impact of CPAP in ‘low-risk OSA’ patients that included all except those with a heart rate response >9.4 bpm or a hypoxic burden >87.1%. The possible underlying mechanism for this observation is, however, unclear. Second, they documented CPAP benefits only in high-risk individuals, especially those without excessive sleepiness and/or hypertension.”
What’s Next?
“Changing the clinical practice is going to require a further prospective study to validate our findings,” Azarbarzin says. “In the meantime, patients with OSA should speak with their doctors to weigh the potential risks and benefits of different treatment options. These conversations can begin the process of personalizing obstructive sleep apnea care and reducing cardiovascular events in this vulnerable population.”
To confirm their findings, Azarbarzin and his colleagues are planning a new clinical trial focused on people with high-risk OSA. They are also investigating how and why CPAP could cause harm in people who do not have high-risk OSA, and they are exploring alternatives to CPAP for treating OSA and lowering cardiovascular risks.
We recommend for you:
ID 135525559 © motortion | Dreamstime.com
