- In a pooled analysis of three randomized trials, CPAP had overall null cardiovascular effects in patients with obstructive sleep apnea and cardiovascular disease.
- However, CPAP leaned toward benefit in those with high-risk sleep apnea, and potential harm in those with low-risk sleep apnea.
- Assessment of sleep apnea phenotype may thus identify patients likely to have a cardiovascular benefit with CPAP.
Cardiovascular benefits and harms could be detected with continuous positive airway pressure (CPAP) treatment for select patients with obstructive sleep apnea (OSA), a pooled analysis of major randomized trials showed.
Without stratifying by OSA phenotype, there remained no secondary cardiovascular effects in the RICCADSA, ISAACC, and SAVE studies -- individually and pooled together -- in patients with concomitant cardiovascular disease (CVD). The risk of major adverse cardiovascular and cerebrovascular events (MACCE) was about the same overall with CPAP or usual care alone (16.6% vs 16.3%; adjusted HR 1.00, 95% CI 0.85-1.18) over a median 3.1 years follow-up.
However, a significant interaction by OSA phenotype indicated that CPAP leaned toward cardiovascular benefit in the high-risk OSA subgroup (15.2% with MACCE vs 17.5% in the usual care group; adjusted HR 0.83, 95% CI 0.66-1.05), with the benefit reaching statistical significance in those with no excessive sleepiness and no increased blood pressure, reported Ali Azarbarzin, PhD, of Brigham and Women's Hospital and Harvard Medical School in Boston, and colleagues in the European Heart Journal.
"Our findings suggest a more personalized 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," Azarbarzin said in a press release.
"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," he continued. "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."
Indeed, the trend was toward harm with CPAP therapy in low-risk OSA (18.2% with MACCE vs 14.9% in the usual care group; adjusted HR 1.22, 95% CI 0.96-1.54). Azarbarzin's group had defined risk according to heart rate response to CPAP or a greater hypoxic burden.
"In people without these high-risk markers, who are already at very low cardiovascular risk, CPAP seems to have downsides," Azarbarzin suggested. "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."
In an accompanying editorial, Andrea Natale, MD, and Sanghamitra Mohanty, MD, MS, both of the Texas Cardiac Arrhythmia Institute at St. David's Medical Center in Austin, nevertheless left room for skepticism about any differential cardiovascular effects of CPAP -- pointing out the poor CPAP compliance in these trials and the very selected study participants not likely to represent real-world patients.
"As lack of perceived benefits and discomfort with the apparatus contribute in a major way to poor compliance with CPAP therapy, and obesity and sleep apnea frequently co-exist, future randomized trials should be conducted including obese patients with moderate to severe OSA (AHI [apnea-hypopnea index] ≥5) to assess the impact of compliant-CPAP vs GLP-1 receptor agonist therapy on symptomatic improvement and reduction in adverse cardiovascular events," Natale and Mohanty wrote.
Patients may be more likely to stay on GLP-1 receptor agonist therapy that can improve their AHI, help them lose weight, and reduce their cardiovascular risk.
Altogether, the RICCADSA, ISAACC, and SAVE studies included 3,549 patients with moderate to severe OSA eligible for inclusion in this post-hoc analysis. They had been randomized 1:1 to CPAP or usual care.
The cohort had a median age of 61 years, and 18% were women. Participants had a median body mass index of 28, a median AHI of 25 events per hour, and a median Epworth score of 7.
For those randomized to CPAP, adherence in the first 24 months was a median 3.3 hours per night.
CPAP adherence was a major limitation of the RICCADSA, ISAACC, and SAVE trials, "thus limiting the applicability of the findings of the current pooled analysis in real-world OSA patients," Natale and Mohanty noted.
The findings may also lack generalizability to women and OSA patients without existing CVD, the duo cautioned.
Disclosures
Azarbarzin reported support from the National Heart, Lung, and Blood Institute; American Heart Association; and the American Academy of Sleep Medicine, as well as grant support from SomniFix, and consulting relationships with SomniFix, Respicardia, Eli Lilly, Amgen, Inspire, Cerebra, and Apnimed.
Co-authors also reported multiple relationships with industry.
Natale is a consultant for Abbott, Biosense Webster, Biotronik, Boston Scientific, Field Medical, Haemonetics, iRhythm, Medtronic, and Pulse Bioscience.
Mohanty disclosed no relevant conflicts.
Primary Source
European Heart Journal
Source Reference: Azarbarzin A, et al "Cardiovascular benefit of continuous positive airway pressure according to high-risk obstructive sleep apnoea: a multi-trial analysis" Eur Heart J 2025; DOI: 10.1093/eurheartj/ehaf447.
Secondary Source
European Heart Journal
Source Reference: Natale A, Mohanty S "Cardiovascular benefit of continuous positive airway pressure therapy in obstructive sleep apnoea: what's new?" Eur Heart J 2025; DOI: 10.1093/eurheartj/ehaf460.
https://www.medpagetoday.com/pulmonology/sleepdisorders/116855
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