[Treatment] The ASV conundrum [ResMed study]

[storywizard]

On the other board there is a thread that details ResMed's failed test on some heart patients with CSA.

here is one news release...

http://www.prnewswire.com/news-releases/...82445.html

and something from ResMed:

http://www.resmed.com/content/dam/resmed...F_FAQs.pdf

has any one here who uses ASV been following this? I am keeping an open mind as a brand new user of ASV, I hope it is not a bad as it sounds on the other board...

Storywizard

[SuperSleeper]

We've been discussing this a bit in our staff forum. I'll re-post the prnewswire article in full after this post so we have a documentation of it if the article disappears.

A question is whether these issues are with ASVs in general or if this is ResMed only that is affected? Just wondering if Phillips Respironics has gone through a similar clinical trial or not?

I'm not certain, but I suspect that the affected persons are are small subset of the overall group of ASV users (being primarily moderate to severe predominant central sleep apnea patients who also have symptomatic chronic heart failure)-- and that there is a bit of unwarranted hysteria out there. Of course, I have no clue as to the veracity of these thoughts, but it will be interesting to follow for sure.

Article posted in next post...

[SuperSleeper]

ResMed Provides Update on Phase III SERVE-HF Study of Adaptive Servo-Ventilation (ASV) Therapy In Central Sleep Apnea and Chronic Heart Failure

Study Did Not Meet Primary Endpoint

Safety Signal of Increased Cardiovascular Mortality Found For ASV Therapy In People With Predominant Central Sleep Apnea and Symptomatic Chronic Heart Failure

Results and Safety Signal Observed Only In This Specific Study Population

SAN DIEGO, May 13, 2015 /PRNewswire/ -- ResMed (NYSE: RMD) today announced that SERVE-HF, a multinational, multicenter, randomized controlled Phase III trial did not meet its primary endpoint. SERVE-HF was designed to assess whether the treatment of moderate to severe predominant central sleep apnea with Adaptive Servo-Ventilation (ASV) therapy could reduce mortality and morbidity in patients with symptomatic chronic heart failure in addition to optimized medical care.

The study did not show a statistically significant difference between patients randomized to ASV therapy and those in the control group in the primary endpoint of time to all-cause mortality or unplanned hospitalization for worsening heart failure (based on a hazard ratio [ HR ] = 1.136, 95 percent confidence interval [95% CI] = (0.974, 1.325), p-value = 0.104). The results from SERVE-HF are preliminary and will be submitted for future publication after further analysis.

A preliminary analysis of the data identified a statistically significant 2.5 percent absolute increased risk of cardiovascular mortality for those patients in the trial who received ASV therapy per year compared to those in the control group. In the study, the cardiovascular mortality rate in the ASV group was 10 percent per year compared to 7.5 percent per year in the control group. There were no issues associated with the performance of the ASV therapy device in the trial.

"Patient safety is our first and foremost priority. We have alerted and are working with appropriate global regulatory authorities about the safety signal observed in this study," said Glenn Richards, M.D., ResMed Chief Medical Officer. "The safety signal in SERVE-HF was observed only with the use of ASV therapy in people who have predominant central sleep apnea and symptomatic chronic heart failure with reduced ejection fraction. We are further analyzing the data to understand why this unexpected result was observed in this trial."

ResMed is working with global regulatory authorities to proactively revise the labels and instructions for use for ResMed ASV devices to include a contraindication for people with symptomatic chronic heart failure (with left ventricular ejection fraction, LVEF, less than or equal to 45 percent). The company is also proactively informing healthcare providers, physicians, and patients of the cardiovascular safety signal observed in SERVE-HF.

The safety signal observed in SERVE-HF was observed only with ASV therapy in patients with moderate to severe predominant central sleep apnea and symptomatic chronic heart failure with reduced ejection fraction. The study did not include people with central sleep apnea in the absence of heart failure. It is also important to note that SERVE-HF did not include any patients with predominant obstructive sleep apnea, and did not include any other treatment modality such as continuous positive airway pressure (CPAP) or auto-adjusting positive airway pressure (APAP).

"SERVE-HF did not meet its primary endpoint, however this study provides valuable, practice-changing guidance on how to best care for people with chronic heart failure," said Prof. Martin Cowie, M.D., the co-principal investigator of the study and Professor of Cardiology at Imperial College, London. "SERVE-HF was a well-designed and executed study and because of it we now know that ASV therapy should not be used to treat central sleep apnea in people with symptomatic chronic heart failure with reduced ejection fraction."

Healthcare providers and patients who have questions or would like more information are encouraged to call 1-800-478-9010 and visit http://www.SERVE-HFFAQs.com

About Sleep-Disordered Breathing
Sleep-disordered breathing encompasses a spectrum of breathing problems during sleep. The two most common types of sleep apnea, a condition that results in repetitive pauses in breathing during sleep, are obstructive sleep apnea and central sleep apnea.

Obstructive sleep apnea (OSA) is a sleep disorder in which the throat muscles relax, block the airways and stop the flow of breath during sleep.

Central sleep apnea is a sleep disorder in which the brain does not transmit the "breathe" signal to the muscles that control breathing during sleep. In some cases, people with central sleep apnea also exhibit an abnormal breathing pattern known as Cheyne-Stokes respiration. With Cheyne-Stokes respiration, there is a period of shallow breathing followed by deep breathing, with intermittent central apnea, in which the breath is stopped for more than 10 seconds during each apnea.

In both obstructive and central sleep apnea, the lack of oxygen causes the person to wake up and start breathing again, interrupting continuous sleep. In central sleep apnea, this occurs more than five times per hour of sleep.

Sleep-disordered breathing is found more commonly in patients with heart failure than it is in the general population, and people with heart failure often report poor sleep as a symptom.

About SERVE-HF
SERVE-HF is a multinational, multicenter, randomized controlled Phase III study that was designed to assess whether treatment of moderate to severe predominant central sleep apnea with ASV therapy in addition to optimized medical care could reduce mortality and morbidity in patients with symptomatic chronic heart failure.

About ResMed
The global team at ResMed (NYSE: RMD) is united in their commitment to changing lives with every breath. With more than 4,000 employees and a presence in over 100 countries, the company has been pioneering new and innovative devices and treatments for sleep-disordered breathing, chronic obstructive pulmonary disease, and other key chronic diseases for more than 25 years. ResMed's world-leading products and innovative solutions improve the quality of life for millions of patients worldwide, reduce the impact of chronic disease, and save healthcare costs. For more information about ResMed and its businesses, visit http://www.resmed.com or follow @resmed on Twitter

Fair Use Applies, from:
http://www.prnewswire.com/news-releases/...82445.html

[DeepBreathing]

From my reading of the statements the problem only applies to people with central sleep apnea and who have chronic heart failure. If you're in that category, I suggest a consultation with your cardiologist. I know my heart is in pretty good nick, and have no plans to stop using my ASV.

[vsheline]

Below is the response from Respironics:


MURRYSVILLE, Pa., May 15, 2015 /PRNewswire/ -- Respironics, Inc., a Philips business, today provided the following response to ResMed's Update on Phase IV SERVE-HF Study of Adaptive Servo-Ventilation (ASV) Therapy in Central Sleep Apnea and Chronic Heart Failure.

On May 13, 2015, ResMed issued a press release and a related Urgent Field Safety Notice. This report described a statistically significant 2.5 percent absolute increased annual risk of cardiovascular mortality for those randomized to a ResMed adaptive servo ventilation (ASV) therapy compared to the control group. In the patient population with LVEF </= 45%, 10.0 percent of the ASV group experienced a cardiovascular death each year compared to 7.5 percent of the control group, representing a 33.5 percent relative increased risk of cardiovascular mortality (HR=1.335, 95%CI=(1.070, 1.666), p-value= 0.010).

Philips is actively evaluating the information provided by ResMed and examining if this might impact the medical care of patients who use Philips BiPAP autoSV/BiPAP autoSV Advanced devices. As part of this ongoing investigation, we are working with ResMed in order to better understand their study data. We are also evaluating post market surveillance data, public adverse event data and other published data to identify and assess other safety concerns that may be present.

Until we complete our investigation, based on the ResMed data, we strongly recommend clinicians adhere to the recommendations that have been published by ResMed and by regulatory authorities cautioning against the use of ASV therapy in patients with symptomatic chronic heart failure (NYHA 2-4) and reduced LVEF</=45%, AND moderate to severe predominant central sleep apnea. ResMed is advising physicians prescribing ASV therapy to not place new patients in the at-risk population on the devices and to evaluate current patients; a discussion about whether to discontinue ASV therapy should occur if a current patient is found to be in the at-risk population. Therefore, as a precaution, physicians should assess individual risks before prescribing BiPAP autoSV/BiPAP autoSV Advanced therapy for the at-risk patient population. No other patient populations have been identified as at-risk for adverse outcomes.

Philips Respironics BiPAP autoSV/BiPAP autoSV Advanced devices are currently indicated to provide non-invasive ventilatory support to adult patients (>30 kg/66 lbs.) with obstructive sleep apnea and respiratory insufficiency caused by central and/or mixed apneas and periodic breathing. These devices are not approved or labeled for the treatment of heart failure.

We will continue to provide updates to the medical and service provider communities as additional information becomes available to ensure the continuous safe and effective use of our devices.

Philips Media Contact

Mario Fante

Email: mario.fante@philips.com

Phone: 1-603-560-9226

SOURCE Respironics, Inc.

[vsheline]

1. People were identified who all have both moderate-to-severe central apnea and Chronic Heart Failure.

2. These people were *randomly* divided into two groups; one group received ASV therapy and the other group didn't. Survival rates were tracked. Four-sevenths of the deaths from cardiovascular causes during the study occurred in one group, and three-sevenths occurred in the other.

Comments:

An unattainably "ideal" study would have studied two equal groups which, if neither group had been treated with ASV, would have had exactly equal survival rates. But, of course, it would have been impossible to know the future and select two groups in this way.

Dividing people into two groups randomly does *not* guarantee equality between the groups. One of the two groups may contain more seriously sick people than the other group. Occasionally, among groups chosen randomly, one group will have many more seriously sick people. The only thing random selection guarantees is that, if the people are randomly divided into two groups many times then *on average* the two groups will be statistically equal.

For example, the first random selection *could* have resulted in putting three-sevenths of the seriously sick people in one group and four-sevenths of the seriously sick people in the other group.

But if the study can be repeated many times, then *on average* we would expect the combined results to indicate whether ASV treatment helps or hurts or doesn't make much difference when the patient also already has a serious and immediate problem like Chronic Heart Failure.

Bottom line for me: I'll be continuing to use my ASV machine until more studies are completed.

[PaytonA]

In view of the numbers Vsheline has reported I would not personally consider the difference significant unless it was over a very large population. I can understand why Resmed might want to raise a red flag so that no one can say that they stood idly by instead of taking action.

Best Regards,

PaytonA

[PsychoMike]

If they only have a total population in the study of 14, divided between two groups and with such a severe issue as CHF already, I'd agree with Payton: I can't see the results as significant esp. if the difference is one fatality in such a limited sample size. Too many variables to assign it to VPAP therapy.

A prime example: for my stats / experimental design class, I went out to test a hypothesis (I actually already knew the what the results should be....well researched topic that deals with a well known physics equation f=m*a) using archery. I got the results I expected, but the sample size was too low for it to be statistically significant (4 set-ups: running a control, 10 lb higher draw weight, 30 gr lighter arrow and both lighter arrow and higher draw...6 arrows each).

Like my study, I think there was something observable, but without a much larger population size I don't think any conclusions can actually be drawn.

[vsheline]

It was a *very* big study.

News Release from 2013:

SERVE-HF; the World's Largest Study of Sleep-Disordered Breathing in Heart Failure Completes Recruitment
Results, expected in 2016, set to demonstrate the impact of effective treatment of central sleep apnea on morbidity and mortality in a heart failure population
AMSTERDAM, Sept. 3, 2013 /PRNewswire/ -- ResMed (NYSE: RMD), a pioneer and global leader in sleep and respiratory medicine, announced today at the European Society of Cardiology Congress 2013, that SERVE-HF has completed enrollment.1 SERVE-HF is an international, randomized study of 1,325 participants investigating if the treatment of central sleep-disordered breathing (central sleep apnea) improves survival and outcomes of patients with stable heart failure.

(Logo: http://photos.prnewswire.com/prnh/20100203/RESMEDLOGO)

Approximately 14 million people in Europe are living with heart failure2 and central sleep-disordered breathing is known to be a highly prevalent comorbidity in these patients. With an estimated 30-50 percent of heart failure patients potentially at risk,3,4,5 the results from SERVE-HF may have important consequences for the future management of these patients.

"Completing recruitment of SERVE-HF has been an important milestone in this landmark trial," said co-principal investigator, Professor Martin Cowie of the Royal Brompton Hospital in London. "We owe much to the commitment and dedication of SERVE-HF investigators and to a strong collaboration between sleep specialists and cardiologists. We now look forward to results in 2016 and to a fuller understanding of just how important the treatment of central sleep-disordered breathing is in heart failure patients."

SERVE-HF will, for the first time, provide conclusive evidence of the health impact of effectively treating heart failure patients who have central sleep-disordered breathing. The trial, which began in 2008, is sponsored by ResMed. Designed as an event-driven study, its completion is anticipated by mid-2015 and results are expected to be available in the first half of 2016.

Central sleep-disordered breathing (central sleep apnea)
Studies have demonstrated that patients with an abnormal waxing and waning breathing pattern, called central sleep apnea with Cheyne–Stokes respiration (CSA-CSR), have a poorer quality of life and increased mortality.6,7,8 Between 30-50 percent of patients with heart failure may suffer from central sleep-disordered breathing,3,4,5 meaning that this condition likely applies to millions of patients across Europe living with stable heart failure. However, studies so far have indicated that treatment of CSA-CSR with PaceWaveTM Adaptive Servo-Ventilation (ASV) during sleep normalizes breathing, controls sleep-disordered breathing, improves cardiac function7 and may lead to increased survival and better quality of life.8,9,10

About SERVE-HF11
SERVE-HF is being conducted across more than 80 sites in Germany, France, the UK, Norway, Sweden, Denmark, Finland, Australia, Switzerland, the Netherlands and the Czech Republic.

The primary goal of the study is to determine whether managing CSA-CSR with ResMed's PaceWave™ proprietary Minute Ventilation ASV technology (found in its AutoSet CS™ and VPAP™ Adapt devices) increases survival rates and decreases the burden of hospitalizations in this patient population. ASV is an intelligent method of non-invasive ventilation that continuously monitors and stabilizes the breathing patterns of individuals with sleep-disordered breathing throughout the night.

"The aim of SERVE-HF is to not only assess survival rates, but also to see if Adaptive Servo-Ventilation improves quality of life, sleep and physiologic changes associated with heart failure," said Professor Cowie. "Additionally, a health economic analysis will be performed to evaluate the potential economic benefits of therapy."

"Given the prevalence of central sleep apnea in heart failure patients, particularly men, its treatment could be crucial to improving heart failure outcomes in the future," added co-principal investigator, Professor Helmut Teschler, medical director at the Department of Pneumology, Ruhrland Clinic, Essen, Germany.

Although there are established links between sleep-disordered breathing and heart failure,9 the diagnosis, treatment and management of sleep-disordered breathing remains in the domain of sleep or respiratory medicine, with a limited involvement of cardiologists to date. The goal of the study is to achieve greater cardiologist involvement in managing sleep-disordered breathing in heart failure patients.

Additional study information, updates and news can be obtained at the dedicated SERVE-HF study website http://www.servehf.com.


SOURCE ResMed Inc.

[vsheline]

From my reading of the statements the problem only applies to people with central sleep apnea and who have chronic heart failure. If you're in that category, I suggest a consultation with your cardiologist.

Yes, and it actually affects only about half of the people with central sleep apnea and who have Chronic Heart Failure, because only about half of the people with CHF also have Ejection Fraction of 45% or less.

Below is a link to a recent article (sponsored by Philips Respironics) saying some doctors have overreacted and unfortunately are now failing to prescribe ASV for their central sleep apnea or mixed sleep apnea patients with chronic heart failure when they should.

http://a360-wp-uploads.s3.amazonaws.com/...Option.pdf

In my own case, I have an echocardiogram yearly or more often and recently the test results showed my left ventricle ejection fraction was less than 45%, unusually low compared to my previous test results. My doctor didn't believe it and had the test repeated with a more experienced technician and the results were well into the normal range.

So I think candidate ASV patients should not rely too strongly on a single test result and should have the test at least yearly, to build up a record.