CPAP Doesn't Prevent Cardiovascular Events in Sleep Apnea, According to the NEJM, But Can That Be True?

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By Gerard J. Meskill, MD

To the many patients who use or have been prescribed CPAP to treat obstructive sleep apnea (OSA), the recently published article from the New England Journal of Medicine (NEJM) may be cause for alarm. This research states that "therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease" (1). In other words, CPAP did not make any difference in preventing a stroke or heart attack in patients with existing cardiovascular disease.

Before you go unplugging your CPAP devices and throwing them in the trash (or out the window), let's take a careful look at the guts of this study. After exclusions and attrition, the study had approximately 2500 participants aged 45-75 (81% men) across 89 clinical centers and 7 countries. All of the participants had pre-existing cardiovascular disease. The following people were excluded: people reporting excessive daytime sleepiness, significant oxygen drops on sleep testing (defined as lower than 80% oxygen saturation for more than 10 minutes of recording time on the sleep study), and people with significant congestive heart failure. What the researchers did was use a home sleep monitor to diagnosis OSA and then an auto-titrating CPAP (or "APAP") to determine the right CPAP pressure to treat those people who were found to have moderate or severe OSA.

Here's where the study becomes problematic. The mean usage time of CPAP for all participants was 3.3 hours. Only 42 percent of study subjects had "good adherence" to CPAP, which was defined as averaging 4 hours of CPAP use per night, but the results were analyzed as if they had all used it. In June of last year, the American Academy of Sleep Medicine and Sleep Research Society published an editorial stating that adults should "obtain seven or more hours of sleep per night to avoid the health risks of chronic inadequate sleep" (2). A recent Gallup poll reflects that only 60% of Americans average 7 or more hours of sleep per night, while 85% average at least 6 hours per night (3). So even using that lower metric of 6 hours per night, the average participant in this study only used CPAP for half the time, on average, and the "good adherence" model averaged compliance for two-thirds of the night.

Think about that for a minute. If you saw a study come out stating aspirin is ineffective for preventing a heart attack or stroke and then found that the participants only averaged using aspirin half the time, you would naturally conclude that perhaps the problem is adherence, not the therapy. Indeed, in the discussion of this article, the authors state "although [an average of 3.3 hours per night of CPAP use] exceeded the estimates in our power calculations, it may still have been insufficient to provide the level of effect on cardiovascular outcomes that had been hypothesized."

In fact, several publications have demonstrated that when CPAP therapy is used adequately, it does reduce the risk of subsequent stroke. Martinez et al. showed that patients with moderate-to-severe OSA who were admitted for stroke and used CPAP had a lower risk of subsequent strokes than those who did not (4). Another study also showed that those with stroke and OSA had greater improvement in function after 30 days if they used CPAP for at least 6.5 hours per night compared to those that did not (5).

While not cited by the study (because its focus was on recurrent cardiovascular events among those with existing disease), do not forget that there is abundant research showing that OSA increases the risk of cardiovascular disease. One study showed the lifetime risk of heart attack doubles if OSA is untreated and triples if the OSA is severe (6). Another study showed that untreated moderate-to-severe OSA increases the lifetime risk of a stroke fourfold (7). And the Sleep Heart Health Study (which is considered the sentinel study on cardiovascular risk from OSA) showed that men with untreated OSA have more than double the lifetime stroke risk compared to men without OSA (8).

As a medical community, we know CPAP is extremely important to treat OSA. It improves sleep quality, quality of life, and work productivity. In fact, the NEJM article acknowledged this: "The reductions from baseline in sleepiness and other symptoms of obstructive sleep apnea were greater in the CPAP group than in the usual-care group," "greater reductions from baseline in the anxiety and depression subscale scores of the Hospital Anxiety and Depression Scale were also observed in the CPAP group than in the usual-care group," "greater improvement in scores on the physical and mental subscales," and "fewer days off from work because of poor health" compared to the usual-care group.

What is amazing about these findings is that sleepy people were excluded from the study, and yet people still reported improvement in sleepiness, depression, anxiety, and work attendance ... even with only 3.3 hours of CPAP use per night! What that demonstrates is that even partial CPAP therapy leads to important improvements in health. The studies referenced above also demonstrate that OSA presents real cardiovascular risk, and appropriate CPAP usage reduces the risk of heart attack and stroke.

What medical researchers need to focus on is how to make it easier for patients to become adherent to CPAP. National statistics on adherence to CPAP are terrible, with some studies showing that as many as 83 percent of patients prescribed CPAP fail to use it for at least 4 hours per night (9). If there's one thing this article proved, it is that haphazard use of CPAP may not be sufficient to protect individuals with pre-existing cardiovascular disease from recurrence of stroke or heart attack.

So before you let this recent publication convince you to stop using your CPAP device, remember that poor use of CPAP is what may have led to these published results in the first place!

1. McEvoy RD et al. "CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea." N Eng J Med. Aug 28, 2016. Epub ahead of print.
4. Martínez-García M, Campos-Rodríguez F, Soler-Cataluña J, Catalán-Serra P, Román-Sánchez P, Montserrat J. "Increased incidence of nonfatal cardiovascular events in stroke patients with sleep apnoea: effect of CPAP treatment." Eur Respir J. 2012;39:906-912.
5. Minnerup J, Ritter M, Wersching H, Kemmling A, Okegwo A, Schmidt A, Schilling M, Ringelstein E, Schäbitz W, Young P, Dziewas R. "Continuous positive airway pressure ventilation for acute ischemic stroke: a randomized feasibility study." Stroke. 2012;43:1137-1139.
6. Yaggi H, Concato J, Kernan WN, et al. "Obstructive sleep apnea as a risk factor for stroke and death." N Engl J Med 2005; 359:2034-2041.
7. Arzt M, Young T, Finn L, Skatrud JB, Bradley C. "Association of sleep-disordered breathing and the occurrence of stroke." Am J Resp Crit Care Med. 172:1447-1451.
8. Redline S, Yenokyan G, Gottlieb DJ, Shahar E, O'Connor GT, et al. "Obstructive sleep apnea-hypopnea and incident stroke: The sleep heart health study. American Journal of Respiratory and Critical Care Medicine. 182(2), 269-77.
9. Weaver TE, Grunstein RR. "Adherence to continuous positive airway pressure therapy: the challenge to effective treatment." Proc Am Thorac Soc. 2008;5(2):173.

Gerard Meskill, MD is a double board-certified neurologist who specializes in the treatment of sleep disorders. He completed his sleep fellowship training at the Stanford Center for Sleep Sciences and Medicine. He now practices sleep disorders medicine and neurology in the Greater Houston area at Comprehensive Sleep Medicine Associates, with offices in the Woodlands, the Houston Medical Center, and Sugar Land, Texas. For more information, visit