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Results of Largest Clinical Trial Evaluating the Role of CPAP In Decreasing Heart Disease Published: How To Interpret the Results?

Posted by SusanR on September 14, 2016 in Research

Studies of the associations between sleep apnea and heart disease in large communities of individuals provide strong evidence that untreated sleep apnea increases the risk of developing high blood pressure, coronary artery disease, heart failure, stroke and premature death. There are known physiological mechanisms to explain how sleep apnea increases heart disease risk, which include injury of blood vessels and the heart muscle. Well-designed studies have shown that treatment of sleep apnea with CPAP improves blood pressure, both day and night levels, particularly in people with difficult to treat hypertension. Since elevated high blood pressure directly increases risk of heart disease, a next critical question is whether CPAP treatment also reduces heart disease, such as heart attacks and strokes.

This question is actually very difficult to answer. Thankfully, relatively few people experience a heart attack or stroke in any given time period. Therefore, to show that a treatment is effective at decreasing these serious events, it is necessary to study very large numbers of people for a long time. Second, in order to establish the effectiveness of a treatment, it is important to study two groups of patients—one group who receives the treatment (CPAP) and one group who receives a different treatment, a placebo (like a sugar pill), or no treatment. Carrying out a large, complex trial requires both significant expertise and experience, as well as resources.

Given these challenges, a highly experienced team of researchers and clinicians from across the globe designed the SAVE trial—The Sleep Apnea Cardiovascular Endpoints trial. The principal investigators were based in Australia and secured funding from the Australian government and Philips-Respironics Inc. They organized teams of cardiologists, sleep medicine physicians, and clinical trialists from 89 medical centers in Australia, South America, Europe, Asia, and the U.S. to work closely together, over a period of over 7 years. They enrolled a total of 2,717 patients, ages 45 to 75 years old, half who received CPAP and half who were untreated. Patients were studied for an average of almost 4 years each, during which time the investigators compared the rates of heart disease events (such as strokes and heart attacks) in treated and untreated groups. Of note, since the study was interested in seeing if rates of heart disease or stroke decreased with treatment, it recruited patients who already had a history of a prior coronary artery or cerebrovascular disease—a group known to have a high risk of subsequent heart attacks or strokes. They also recruited patients who had at least moderate sleep apnea (defined by at least 12 drops in oxygen levels per hour at night) and patients who showed they were able to tolerate wearing a CPAP mask. Patients who were given CPAP used it on average for 4.4 hours during the first month of treatment, but usage decreased over time, with average use of only 3.3 hours per night over the period of treatment.

What did the study find? After a mean of 3.7 years of follow-up, the rate of heart disease events did not significantly differ for those who received CPAP or those who were untreated. However, patients treated with CPAP experienced significant improvements in sleepiness, anxiety and depressive symptoms and quality of life. Moreover, a sub-analysis restricted to patients who wore CPAP at least 4 hours a night for the first two years of treatment showed that CPAP reduced risk of strokes by about 40%.

What might these findings mean to you? When hearing about a new research study, it is important to ask how the patients in the study compare to you. The SAVE trial enrolled patients with known heart disease or stroke, enrolled people with relatively few symptoms from cardiology centers, and from mostly centers outside of the U.S. (predominantly in Asia). Achieving high levels of CPAP adherence for 89 international centers is a challenging task for a study to undertake, and despite strong efforts by the study team, average CPAP adherence was less than 4 hours per night over each person’s 3 to 4 years of follow-up. Rather than conclude that “CPAP does not help” it would be more appropriate to conclude that inadequate use of CPAP in patients who already have developed heart disease is unlikely to influence the risk of a heart attack over a 4 year period. However, based on the known beneficial effects of CPAP on blood pressure, it is reasonable to expect that CPAP could reduce the risk of heart disease if it is used for the entire sleep period—including times like the early morning, when REM sleep may cause particularly severe apneas and cardiovascular stress. Although this question needs to be examined with additional research, the study's finding from a secondary analysis showing that stroke risk was reduced in patients using CPAP for at least 4 hours per night does provide support for this. The beneficial effects on sleepiness, mood and quality of life –despite relatively low average CPAP usage—also provide a strong incentive to use CPAP. Finally, it is very possible that CPAP may be most effective in patients who have not already developed heart disease (as did the subjects of this study). The surveys that MyApnea.Org members have completed tell us that a majority of patients report that they had sleep apnea for many years before being treated. Prolonged periods of time when sleep apnea is not treated may cause damage to the blood vessels and the heart that may be hard to reverse.

We also interpret the data as indicating the need to find ways help to patients get their sleep apnea diagnosed and treated earlier in life and before the onset of heart disease, help patients better adhere to their CPAP, and to continue to research new ways to treat sleep apnea that are well tolerated and effective. We also recognize that new studies will be needed to study the effects of more effective levels of CPAP and other treatments on important health outcomes, like heart disease, in patients both with and without known heart disease.

We ask you to stay involved in MyApnea.Org and let us know how together we can solve this important questions.

References

  1. McEvoy, D.R et a, CPAP for the Prevention of Cardiovascular Events in Obstructive Sleep Apnea. New England Journal of Medicine, Aug 28, 2016

This article was written by Dr. Glaucylara Reis Geovanini, MD, P Lehmann Fellow in Cardiology, and Dr. Susan Redline, MD, MPH, Professor of Sleep Medicine, Harvard Medical School, MyApanea.Org Principal Investigator and Steering Committee Co-chair. Read the full New England Journal of Medicine article here.

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[-] Sherry +2 points · 8 months ago

It is so unfortunate that the SAVE study drew a conclusion based only on CPAP Patients who only complied with treatment for 3 to 4 hours per night. Having been a sleep apnea patient for 25+ years, there have been times throughout those years that I have not been committed to C-PAP usage on a regular basis. There have also been times when I have been very committed to be inconvenienced by C-PAP usage. I am very aware of underlying conditions that have been shown to be caused as a result of sleep apnea. However, to know and not to do, is really not to know. I can ignore the data, studies and research in my mind but I cannot deny the way my body feels when I am committed to adherence vs. how my body feels when I am not. I also experience both physically and mentally a great difference in how my body feels when I have used CPAP 4 hours or less vs. 7-8 hours. If I am mentally and physically aware of the shortage of hours, I am certain that my organs must be knowing and responding to the difference as well. Thank you Dr. Redline for digging a little deeper beyond the surface conclusion of this study.

   
[-] MarkHanson +2 points · 9 months ago

I have read the study results and was concerned how they might be interpreted. I commend Dr Redline for the clarity and concision of this reflection on the study. My person experience supports the observations: using CPAP helps, more hours per night increases benefits, and it takes time to realize benefits. Next Steps: we need a truly extensive longitudinal study that like the Framingham Heart Study which eventually spans whole lives and even generations of families. How far back did medical awareness even recognize Sleep Apnea as a condition, how recently was there a therapy that worked, how present is Sleep Apnea in the public consciousness? When was ensuring CPAP therapy be maintained during one's post surgical treatment in hospital even considered: is it yet a norm? I am in my seventh year of treatment. I have witnessed changes in so many areas, and collaborating with other patients, clinicians, and scientists presents me with an ever broader and more informed perspective on the issues with Sleep Apnea, and the benefits of systematic use of CPAP. My read on this is to strongly affirm that we need to Stay The Course and even Double Down.

   
[-] Verne7 +1 point · 8 months ago

Wow, amazing. I am dumbfounded when I read that the cpap is KNOWN to help uncontrollable high blood pressure and yet my supposed sleep "doctor" would not prescribe the treatment for my uncontrollable high blood pressure and recently developed Afib (high). According to her, I needed to have so many periods of stopping breathing before she would give me the prescription. She simply said she would not do it for blood pressure or afib. Both my regular doctor and cardiologist were certain that cpap would help both of those. Isn't refusing treatment somewhat against the oath doctors are supposed to take?

   
[-] JudyBJ +0 points · 7 months ago

Verne7, get a different sleep "doctor"! Your regular doctor and cardiologist are right. The connection between having sleep apnea and its negative effect on Afib (and your heart) are well-known. I practically had to force my former sleep doctor (a pulmonologist) to lower the pressure on my CPAP machine so I could use it at all. The man and his office staff were all very nice but useless in terms of helpfulness.

   
[-] Exhausted2 +0 points · 6 months ago

I got them to lower mine from 21-17 the first week to 16-12 now the last three weeks, It's still high but, but I'm using it more, and having only 2 to 5 episodes an hour. So I'm hoping they don't want to raise it back up.