[Diagnosis] ATRIAL FIBRILLATION - CONTRARIAN VIEW?

[srlevine1]

From a well-respected contrarian medical Substack blog known as the Skeptical Cardiologist, authored by board-certified noninvasive clinical cardiologist Dr. Anthony Pearson.

["For the last 13 years my practice has been at St. Luke’s Hospital in St. Louis but as of September 1, 2020 I have transitioned to Saint Louis University SLUcare. For what it’s worth I’ve been named to the Best Doctors in America list annually from 2009 to the present.]

Does Treating Sleep Apnea With CPAP Improve Cardiovascular Outcomes or Lower Risk of Atrial Fibrillation? 

The sleep apnea industry would like you to believe that it does but high quality data show that CPAP is ineffective in improving cardiovascular outcomes for most individuals

Despite the widespread belief that obstructive sleep apnea (OSA) causes cardiovascular events like strokes and heart attacks, there is no good evidence that treating OSA lowers the risk of such cardiovascular outcomes.

Observational data showing that OSA is associated with cardiovascular outcomes like atrial fibrillation, stroke, CV death, and myocardial infarction have been utilized by the sleep apnea academic-industrial complex (in ways very similar to the omega-fatty acid (OMFA ) academic-industrial complex) to market the need for sleep apnea diagnosis and treatment.

However, as we saw in the OMFA world, causality can only be proven with a randomized trial of effective therapy of the disease (given that there is no way to randomize patients to having OSA or not having it.) The most widely prescribed and effective therapy for OSA is continuous positive airway pressure (CPAP).

Healthy User Bias is a major confounder of most CPAP and all observational studies as noted at ClinicalCorrelations

Observational studies have demonstrated that among patients with OSA, CPAP is associated with a lower incidence of fatal and nonfatal cardiovascular events. A recent meta-analysis of observational studies corroborated these findings, noting a hazard ratio (HR) of 0.37 (95% CI, 0.16 to 0.54) for cardiovascular mortality in CPAP treated patients compared to untreated patients. However, these studies are marred by their lack of randomization. Therefore, the patients compliant with CPAP may have enjoyed their cardiovascular benefit from any number of downstream effects of their general aptitude towards making healthy lifestyle choices (the healthy user bias) rather than from CPAP alone.

A recent draft document on CPAP therapy for OSA from the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services outlines some of the major unresolved questions:

Obstructive sleep apnea (OSA) is a disorder characterized by periods of airflow cessation (apnea) or reduced airflow (hypopnea) during sleep. The diagnosis and severity of OSA, and response to therapy, are typically assessed using the apnea-hypopnea index (AHI). However, no standard definition of this measure exists, and whether AHI (and associated measures) are valid surrogate measure of clinical outcomes is unknown. OSA is commonly treated with the use of continuous positive airway pressure (CPAP) devices during sleep. The efficacy of CPAP, including for Food and Drug Administration (FDA) clearance/approval, has been based on changes in AHI, but the long-term effect of CPAP on clinical outcomes and the role of disease severity (as measured by AHI) or sleepiness symptoms on the putative effect of CPAP are unclear.

After looking at 47 studies on this question, the AHRQ review concluded that there was no evidence to support the idea that CPAP treatment lowers “clinically important outcomes.”

The published evidence mostly does not support that CPAP prescription affects long-term, clinically important outcomes. Specifically, with low SoE (standard of evidence) RCTs do not demonstrate that CPAP affects all-cause mortality, various CV outcomes, clinically important changes in psychosocial measures, or other clinically important outcomes. 

And there isn’t evidence that CPAP treatment of OSA influences individual aspects of CV disease, including atrial fibrillation, which counters the mantra that sleep centers and atrial fibrillation experts have been spouting for years:

Insufficient evidence exists regarding effect of CPAP on the risk of transient ischemic attack, angina, coronary artery revascularization, congestive heart failure, and atrial fibrillation.

In fact, the two randomized controlled trials (RCTs) that report atrial fibrillation came to opposite conclusions with one showing it lowered risk and the other one showing that CPAP raised the risk of developing atrial fibrillation!

Pretty much everything. you thought would be helped by CPAP treatment has not been proven says the AHRQ

Regarding other assessed outcomes, CPAP does not affect the risk of driving accidents or the risk of incident diabetes (both low SoE). CPAP does not result in clinically significant changes in depression or anxiety scores, executive cognitive function measures, or nonspecific quality of life measures (all low SoE). There is insufficient evidence regarding the effect of CPAP on incident hypertension, functional status measures, male or female sexual function, or days of work missed.

There is a clear and obvious way to prove that diagnosing OSA matters (beyond improving daytime sleep and snoring) and that OSA is a life-threatening disease and that is to randomize patients diagnosed with OSA to treatment with effective therapy (CPAP) and several of these have been performed. Unfortunately for the OSA business, the results of these RCTs do not show a benefit of therapy, consequently sleep experts/centers and businesses that sell OSA diagnostic and therapeutic equipment tend to gloss over, dismiss, or ignore these data.

Clinical Correlations does a good job of summarizing the methods and outcomes of the major randomized trials for those interested and they concluded:

Recurrent patterns emerge from these data reviewed here. Typical use of CPAP does not ameliorate the risks of fatal and nonfatal cardiovascular events in patients with OSA, though it may reduce symptoms of daytime sleepiness and snoring. Subgroup analyses of patients wearing CPAP over 4 hours per night suggest that CPAP may lower cardiovascular events; however, these findings are subject to significant bias

Post-hoc subgroup analyses like the association of CPAP usage >4 hours with lower events cannot be used to prove causality; they should serve as hypothesis-generating. 

However, if your business is diagnosing and treating sleep apnea you are highly biased to cherry-pick the available studies.

Thus, although the nonbiased writers of the main analysis section at Clinical Correlations came to the proper conclusion: no benefit, a pulmonary/sleep medicine MD “commentary” addition concluded the exact opposite:

As multiple studies have shown, treatment of OSA with CPAP has numerous cardiovascular benefits, including arrhythmia control and prevention of recurrence, improved glycemic control, and reduction of the risk for stroke and MI.

This pro-sleep apnea treatment commentary focused on the CPAP>4 hour subgroup analysis without admitting the severe bias this introduces and without discussing how common this is.

Since these analyses were made another RCT has been presented.

This study enrolled 111 consecutive patients with OSA and a history of atrial fibrillation and randomized them to either receive CPAP therapy or no CPAP therapy for OSA. All patients had an implantable loop recorder (ILR) implanted which allows the continuous recording and quantitative measurement of the amount (duration or burden) of atrial fibrillation.

CPAP therapy, even when the patient was highly compliant had no effect on the recurrence of atrial fibrillation (AFIB.)

Screening and Marketing of OSA

Here’s an online heading and opening story about a study that found a huge percentage of AF patients had OSA.

Read more...

Conclusion...

To summarize and answer the question in my title:

Despite numerous flawed observational studies suggesting an association between sleep apnea and cardiovascular outcomes including atrial fibrillation the gold standard, high-quality RCT data do not clearly show that treatment of sleep apnea with CPAP improves cardiovascular outcomes.

Until good scientific evidence proves that treatment of OSA really does save lives, and reduces heart failure, atrial fibrillation, or other important cardiovascular outcomes, widespread screening and marketing for the diagnosis and treatment of OSA other than for reducing snoring and daytime sleepiness should cease.

Somnoapoplectically Yours,

-ACP

N.B. There are definitely patients with very severe OSA whose lives are drastically improved from CPAP therapy. I have patients who have been radically transformed by the treatment.

I am not discounting these cases. This article is focused on the patient with mild OSA who has been sold a bill of goods on how CPAP therapy can save their life.

N.B. 2 It is rare to find an authority in sleep apnea who will be honest about this topic. As such, it was very refreshing to have a reader share with me a brilliant article on Medscape written by Dr. Aaron Holley entitled CPAP Therapy Oversells and Underperforms.

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC.

His summary paragraph is spot on:

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions — prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: "If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe." All other indications are soft.

There are always exceptions and I would not rely on one opinion or series of articles to make the decision to discontinue CPAP therapy without medical consultations with my team: Primary care physician, cardiologist, electrophysiologist, pulmonologist, hemotologist, etc. And, second opinions.

[Sleeprider]

Well, initially, my decision to pursue CPAP was a solution to snoring that threatened to ban me from the same bedroom with my wife. The benefits of treating my "very severe" sleep apnea some 16 or so years ago, may not have resulted in a "significant" clinical outcome, but I'm not about to give it up. I suppose I'm not an "unblinded realist" because I have experienced a night without therapy, and I can't imagine Dr. Pearson has any perception of the discomfort and stress that causes. It's clearly of no medical consequence to him.

[SheShells23]

Welp, you've officially burst my bubble and rained on my parade just as I completed a whopping day 3 of CPAP therapy...
I just was diagnosed with Afib in 2023. I actually have no classic signs of sleep apnea that are on every intake survey.

I have insomnia, chronic sleep deprivation, and wake several times a night.
My sleep studies have me at mild sleep apnea - around 12.1 for AHI. Little to no snoring.

My cardio is highly educated and progressive but because my Afib episodes are usually always in the middle of the night, she wants to be sure they are not triggered by hypoxic events.

Anywho, the nice big scientific wet blanket was extremely ill-timed for me to say the least...

[srlevine1]

Anywho, the nice big scientific wet blanket was extremely ill-timed for me to say the least...

You need to consider the sage words of Carl Sagan, “Absence of Evidence does not mean Evidence of Absence." 

The treatment prescribed by your doctor is probably right for you, especially as a preventative. In my estimation, having and using a device is preferable to not having and using a device until you experience an adverse life-altering effect. 

I would be interested in seeing your OSCAR data and to know if you are using a recording pulse oximeter to detect nocturnal oxygen desaturation.

Stand easy and stay the course. Best of luck. -- Steve

[BoxcarPete]

Well, Sleeprider, that's probably because you have polluted the purity of the experiment by caring about your health in other ways in the meantime.

I don't quite understand the logic behind the demands for such stringent rigor for clinical proof that CPAP is helpful. The effects of OSA are cumulative over the course of years, if not decades. The randomized OSA patient study where they gave CPAP to some and not to others probably only lasted a few months at most, though the duration of the study is not stated in the article. It's unsurprising that they wouldn't find anything in a short time, and if they were to do such a study for a sufficiently long time, provided they found a way to do it ethically, he already indicated that he'd be inclined to throw the results of that out, too! There's no way to control for all the other factors over the course of a decade, so why not just cry "Healthy User Bias" and discredit the findings?

That said, I agree with him to some extent, that CPAP is over-prescribed, especially in the cases of mild OSA and UARS. It seems like sleep doctors in this country just formulaically say "AHI>5 = CPAP. Don't like it? I dunno, try an MAD if you want." There are so many potential contributing factors (particularly with younger generally healthy people and anyone with UARS) that CPAP doesn't fully address, and many of which MAD fails to address at all. It does often seem like a big machine rather than patient-focused care, but bashing the effectiveness of CPAP based on the fact that a particular government agency has yet to prove the unprovable with sufficient scientific rigor doesn't seem productive to me.

$.02

[Sleeprider]

BoxCarPete, those are very good points, and the endpoint for the study being a change in cardiovascular health as measured by A-fib seems both limited as compared to most individual's expectation of therapy, and difficult to prove in the long-term. We need to accept that Pearson’s study is limited to a cardiovascular endpoint for a-fib and does not speak to anything else.

You are in a position to judge the therapy from the perspective of someone with mild sleep disorder, that seemed to be resolved in large part by excavating your nasal passages. I don't think that, or ignoring the problem is much of a solution for the many individuals with a severe or very-severe diagnosis. With regard to over-prescription, my experience on the forum is that some of the people seeing to improve their sleep and how they feel, are stridently convinced that the solution lies with CPAP therapy. Even when that therapy is optimal, they will continue to blame their sleep disordered breathing for continuing fatigue, sleepiness or other malapropism. (I hope you know what I did there). Anyway, it's often easier to acquiesce than to deny the therapy or convince someone their problems may lie elsewhere.

[srlevine1]

Healthcare by the numbers is always a probabilistic crap shoot (pun intended) due to individual physiology, temporal, and confounding factors. However, part of the scientific method is to suggest a hypothesis and then go about designing an experiment or making correlative observations to verify, falsify, replicate, or simply inform and make others think about alternatives.

As for BoxcarPete, who claims to not "quite understand the logic behind the demands for such stringent rigor for clinical proof that CPAP is helpful," the demands for rigor arise from the scientific method and the necessity of building a testable hypothesis as well as a framework for understanding the results. Without such rigor, everything remains in the realm of opinion that may or may not be helpful in diagnosis and subsequent therapy.

What one does with the Pearson article is a personal choice and serves only to spark thought and discussion. Perhaps, a reader will ask their physician an informed question or seek a second opinion.

I, personally, would like to see the subject matter presented for consideration rather than continue down a blind path in darkness. I guess it remains a question of correlation versus causation.

[BuzzaJim]

Welp, you've officially burst my bubble and rained on my parade just as I completed a whopping day 3 of CPAP therapy...

Anywho, the nice big scientific wet blanket was extremely ill-timed for me to say the least...

Everyone has an opinion and Dr. Pearson’s is extremely strong.  It’s not much more than that. Cpap doesn’t prevent Afib but it sure makes it a lot easier to manage/live with.

My situation is very similar to yours.  I was first diagnosed with AFib 10 years ago but didn’t start Pap therapy until last year.  My AHI was 14.8 when I started therapy.

The only reason I had the sleep study was because nothing else was working anymore.  The first five years were without reoccurrence then things got progressively worse. After two ablations, too many cardio versions and numerous changes in medication, my paroxysmal Afib was becoming very persistent.  What was particularly troublesome for me was my heart rate variability was getting very erratic while I attempted to sleep, even in normal sinus rhythm.  I was seeing crazy rises in heart rate, nocturnal de-sats and was waking up pretty much every hour.

Lucky for me, my normal cardiologist couldn’t keep an appointment so I saw a Nurse Practitioner instead.  She actually listened and suggested I be screened for sleep apnea.  My PCP didn’t think I fit the profile for sleep apnea but made the referral based on the very low blood oxygen levels my Apple Watch was catching as I slept (well below 80%)

It was nearly five months before I had a machine to begin therapy but it changed everything from the first night.  My heart rate variability immediately dropped to a normal level while I slept and my blood oxygen levels stayed above 92%.  I was sleeping a lot better and had a lot more energy for my morning workouts.

I didn’t have a reoccurrence of Afib for 5 months and when it finally came back, events were a lot easier to deal with.  Even with Afib, my nocturnal blood oxygen stays above 90%.  The sleep isn’t perfect but is so much better than it was and because of this forum is still improving. My AHI is consistently below 1.  To paraphrase an old saying, they will never take my machine until they pry it from my dead fingers

I’m sure Dr. Pearson would point out my story is anecdotal.  There has been no randomized, double blind study, but there are a lot of things we take for granted in life where no such study has been done.  I know what’s working for me and hopefully it will for you.  It sounds like your cardiologist is on top of this.  Give it time

[G. Szabo]

Paper title:
Does Treating Sleep Apnea With CPAP Improve Cardiovascular Outcomes or Lower Risk of Atrial Fibrillation? 
 
"CPAP does not result in clinically significant changes in depression or anxiety scores, executive cognitive function measures, or nonspecific quality of life measures (all low SoE)."
 
Comment:
The above is an interesting statement because several "clinical trials" conducted in the prisons of some oppressing regimes in the late twentieth century demonstrated the extreme effectiveness of sleep deprivation and sleep interruption as torturing techniques. It is even used today during some police interrogations in some underdeveloped countries. This technique resulted in forced testimonies and false guilty pleas. 
 
Can someone make a false plea without significantly changing the "executive cognitive function"?

[BoxcarPete]

I well understand the need for the scientific process. The problem I have with Dr. Pearson is that he demands a far greater burden of proof from everyone else than he is willing to put forward himself. There aren't enough double-blind randomized controlled trials of afib patients who also have OSA with and without CPAP to satisfy him that CPAP is a legitimate treatment option for afib. That's a completely acceptable position to take.

What gets me is that he discredits CPAP as a treatment in general with barely a wave of the hand despite the data we actually have: that is, follow-up studies which conclude that there is an overall difference in outcomes for people who have used it compared to people who were non-compliant. He tosses out the assertion that those who were compliant probably made better life choices in general so of course they are going to have better health outcomes and then refuses to back up his position at all, while demanding the highest level of rigor from anyone who wants to say otherwise. The cited source for this position lists study after study on the subject and they all come to the same conclusion: not enough data to confirm that patients had significantly better cadiovascular outcomes when prescribed CPAP, except for those patients who used it an average of 4 hours or more per night. Those patients consistently had a robust and significant reduction in adverse outcomes (RR, 0.58; 95% CI, 0.34 to 0.99); (RR, 0.70; 95% CI, 0.52 to 0.94); (HR, 0.29; 95% CI, 0.10 to 0.86); (HR of 0.37; 95% CI, 0.16 to 0.54). It's disingenuous in my opinion to call this "cherry picking" when there is such a clear indication of efficacy when used as directed, despite a lack of benefit when non-compliant patients are also considered. I wonder if he would go to bat in the same way sleep doctors have for CPAP if his go-to medication were to have an RCT come back with the conclusion that it only helps if used as directed.

The whole tone of the article indicates that Dr. Pearson seems to believe that CPAP isn't a worthwhile treatment in general (except for snoring or whatever), and it's just a money grab. His claims to that end are hardly substantiated by the fact that non-compliant patients are more prevalent in hose-heads than pill-poppers. I am a firm supporter of CPAP alternatives and I think they should be given more consideration than a non-comittal shrug from your friendly neighborhood sleep specialist, but CPAP works for many people, and the very studies he claims prove that it's ineffective show that when it works for a patient, it provides all the benefits as claimed.