01-04-2018, 09:42 AM
ASV discussion
Larry, your doctor's characterization of "an awful side effect of dying early therefore he said all docs were very suspect of ASV's" is grossly over-simplified, and a misapplication of the available data. During a large trial (SERVE-HF) of central apnea patients, it was found that there was a statistically significant increase in sudden cardiac death amongst a specific cohort of patients with congestive heart failure and left ventricular ejection fraction less than 45%. This study has been criticized for a number of variables in terms of treatment efficacy, machine usage and other factors, but the warning specific to the affected population of CHF w/ <45% EF remains in effect.
This warning is not applicable to otherwise healthy central apnea patients with treatment onset of central or complex apnea with CPAP treatment. Nevertheless, a normal part of screening for use of ASV now includes evaluation using echocardiogram to ensure you do not fall within the "at-risk" pool. Generalizing that risk to all users of ASV is both inaccurate and a disservice to the many individuals that benefit from the therapy, and realize health benefits consistent with resolving complex and central sleep apnea. You should do your own research to be able to discuss this and evaluate your own risk and risk-tolerance. https://www.google.com/search?q=SERVE-HF...e&ie=UTF-8
Some sleep specialist doctors would consider that statement to be an oversimplification. For example, see this statement by M Safwan Badr, MD (bold added by me):
At the same time, Dr. Badr had the following to say about the results of Serve-HF:
In summary, I think he and many others would say the following:
1) SERVE-HF provides enough clinical reason to withhold ASV from the great majority of patients with EF < 45% pending further studies. Unfortunately the SERVE-HF results have caused some regulatory agencies to ban similar research. That is likely premature and should be considered in light of SERVE-HF limitations and weaknesses.
2) SERVE-HF provides a safety signal worth of concern and discussion prior to ASV use in patients with normal EF but is not a good reason to withhold ASV treatment from most such patients.
Similar criticisms can be made about virtually all sleep apnea trials, and the authors addressed those criticisms in the author's reply on this page: http://www.nejm.org/doi/full/10.1056/NEJ...b%3dpubmed
And we should keep in mind that the same variables in machine usage and treatment efficacy are likely to exist in the population of patients for whom this therapy would be prescribed. Plus it goes both ways: just as greater adherence and lesser crossover may have decreased the magnitude of observed mortality risk, it may just as likely have increased the magnitude of observed mortality risk.
Yes, there are weaknesses and limitations, but this was a well done study accepted for publication by the highest impact clinical journal in the world. Most sleep medicine experts consider the findings to be important enough to guide clinical practice in patients with CSA and EF < 45% pending additional study. And just as I have a bit more skepticism for any positive data coming from a drug study funded by the drug maker, I look with a bit less skepticism on negative data coming out of a device trial which was funded in part by ResMed.
When the death rate with low ejection, was 5 times higher than not using one. Those are extreme odds. It really is a big red flag and shouldn't be taken lightly. ASV at this point of time shouldn't be used and no doctor in his right mind would risk his patient, nor open himself up to such a law suit. Ethics wouldn't allow another trial. The results are already known, they are just a bit uncertain as to why. The conciseness is, those with low ejection, should be excluded for their own safety.
I'd watch the whole thing, but this is the statement.
https://youtu.be/Nr08K5IfzzY?t=2137
Prof Simonds comments on the results of the SERVE-HF trial and also discusses the different uses of ASV as therapy for complex sleep apnoea, central sleep apnoea, and opioid-induced sleep disordered breathing. She notes that significant findings have been made regarding the correct usage of ASV, but acknowledges that more work is required in this area.
Ajack, the safety signal is strictly for CHF patients, and the absolute total risk increase was 2.5%. That is 2.5 in 100 or half your claimed 5X risk. This was said to be a 33.5% relative increase in risk according the the Philips Response (http://incenter.medical.philips.com/docl...3D11360660 ) Again, this risk cannot be extrapolated to individuals outside that risk cohort. I will wait for the Reader's Digest version of that 1-1/2 hour video.
edit to note, in my statistical world a 5X increase is 500% over a control, not 33%. Not disputing the significance and concern, particularly for those with CHF and LVEF<45%. You seem to infer ASV should be not be used on anyone under any circumstances.
Again, the risk cannot be definitively extrapolated to individuals outside that group, but it remains to be seen whether individuals outside that cohort may also be at some risk.
Or as Dr. Badr put it:
He wouldn't advise doctors to inform such patients of the safety signal if we could be 100% sure that it is not relevant to those patients.
Many things in medicine are like that. I treat patients with a medication called exenatide, which causes a rare type of thyroid cancer in rodent studies. Human studies don't show that it causes thyroid cancer in humans, but given a lack of certainty that the rodent data is irrelevant to humans, I inform patients of the animal studies so they can make a fully informed decision.
Part of helping people with normal heart function to make a fully informed decision about ASV is letting them know that it was associated with an increased risk of death in people with a certain type of heart disease and that since we don't know why that was the case, we cannot be certain that it has no risk in other groups.
So as the patient not having a clue what to do would say "What do you recommend?".
perhaps if you looked at the video and saw the referenced study, you would see the 5 fold death risk of using the asv. It really isn't an option for those with reduced fraction. It really is like russian roulette. It is even worse for those that didn't have defib fitted, the hazard ratio was "astronomic".
FWIW Knowing what I do about the risks on both sides of choosing ASV to treat Apnea where indicated it's needed or not treating via ASV because of the risks due to heart deficiencies, I'd choose treating vs not. This is for me myself only. I'd rather try than not. Why would I say that? If both of my choices meant increased likelihood of death, I'd still try the method that might prolong life. I've lived a long time under the restricting influence of apnea, and a few months feeling better on ASV and getting apnea treated successfully, and I'm certain I'll choose treating via ASV rather than the pathetic "life" I endured beforehand.
Having said that, I'm not choosing for anyone else but me.
Dave
There are all different kinds of patients. Some only care about "What do you recommend" and ignore the rest. Others would rather go without treatment than to take a treatment with a risk, even if that treatment risk is lower than the risk of non-treatment and the doc recommends treatment. And that is their prerogative, IMO.
So if a person with hyperventilation-related CSA and normal EF had a poor outcome with CPAP with or without oxygen (as well as addressing identifiable root causes), I would explain to them the known and possible risks including a discussion of the SERVE-HF safety signal and the possibility that it means there is a related risk involved for them.
In the context of that discussion, I would likely recommend ASV, but I don't think it would be right of me to say that the safety signal was irrelevant to them.
Discounting a 5 fold death risk, where the study was terminated 5 years earlier than planned, because of the ethics and liabilities is strange. I'm certain resemed didn't support this finding for the fun of it. No doctor would suggest a 5 fold risk, when other treatment options are available.
Shin, It may well be that you are who you say you are. Personally I'd prefer the forum admin to either ask for confirmation of being board certified or ask the forum member not to say they are in any way medically qualified. After all this is the internet, where 12 year olds are fighter pilots.
If I recall, one of the comments made in the video was that the problem with the study may have been due to the fact that healthy patients were removed and unhealthy left in the study, hence, the results of ASV looked bad.
Furthermore, I missed the part where they were able to pin point the reason that ASV was causing premature death rate in those with EF of <45%. Without a reasonable explanation, the study is inconclusive, in my opinion.
Healthy patients can use an asv. There is no reason for a healthy person to be concerned. This was looking at a sub group with an ejection factor under 45%. There is no pin point, there was the clinical finding that 5 times the death rate with low ejection. 4 out of 12 in this subgroup died and the trial was cancelled, with the support of the manufacture who funded it. The manufacture then went on to issue a warning to not use their machine for these patients. I don't know if everyone realises the significance of a 5 fold finding. There really isn't any debate at this stage, until further work is done or new treatments for this subgroup are found. They are prescribed the ST mode.
The greater than 5 hazard ratio (HR) mentioned in the video refers specifically to patients with EF ≤ 30% without previous hospital admission. This was not part of the original publication but rather the result of a subsequent multistate modeling analysis study meant to help understand the mechanism of the findings from the original publication. The HR for the risks noted in the original study was ~1.3.
We have to be careful about things that come out of the subsequent analyses of a randomized controlled trial (RCT). There's a reason why primary and secondary endpoints are designated at the outset. Otherwise I could take their data set and interrogate it with questions like:
-Was being a Pisces associated with early death with ASV?
-Was being born on a rainy day associated with early death with ASV?
-Was being of German descent associated with early death from ASV?
Surely if I asked enough questions of the data, one would come up with an association with a p value less than 0.05. Such is the nature of chance and is the reason they pick their questions in advance of doing the study.
Now I am not suggesting that the multistate modeling they did was gibberish, throwing stuff against the wall to see what stuck. These are reputable scientists publishing in a very good journal (Lancet Respiratory Medicine), so they must have used legitimate statistical methods. But it isn't the same as designing an RCT with a primary endpoint of cardiovascular death in patients with EF ≤ 30% without previous hospital admission.
-Was being a Pisces associated with early death with ASV?
I'm a Pisces. Could we use a Leo for the example instead please.
I'm a Pisces too, ha
.
Let me be very clear that I am NOT a sleep specialist and that nothing I say here should be taken as medical advice. I have changed my signature to reflect that fact. Unfortunately the board software doesn't automatically apply the new signature to all my old posts, and they are beyond the window where I can do so.
I have mentioned that I am a doc here a couple times out of full transparency so that when people are badmouthing docs here and I say otherwise, people can tell where my potential biases lie. Also, I was giving some perspective about how docs may talk to patients.
But I am an endocrinologist (hormone doc), not a sleep specialist. When it comes to sleep apnea, I am a patient, and I am learning here as I go. If anyone wants me to prove that I'm an endocrinologist, feel free to PM me for that. But I'm not going to give medical advice here about my field either.
This warning is not applicable to otherwise healthy central apnea patients with treatment onset of central or complex apnea with CPAP treatment. Nevertheless, a normal part of screening for use of ASV now includes evaluation using echocardiogram to ensure you do not fall within the "at-risk" pool. Generalizing that risk to all users of ASV is both inaccurate and a disservice to the many individuals that benefit from the therapy, and realize health benefits consistent with resolving complex and central sleep apnea. You should do your own research to be able to discuss this and evaluate your own risk and risk-tolerance. https://www.google.com/search?q=SERVE-HF...e&ie=UTF-8
(01-04-2018, 09:42 AM)Sleeprider Wrote: This warning is not applicable to otherwise healthy central apnea patients with treatment onset of central or complex apnea with CPAP treatment.
Some sleep specialist doctors would consider that statement to be an oversimplification. For example, see this statement by M Safwan Badr, MD (bold added by me):
Quote:ASV remains an option in patients with hyperventilation-related CSA and a preserved ejection fraction, although treatment decisions in such patients should be individualized, and there is a paucity of direct data in these patients [15].
Patients who are already using ASV for other indications (eg, heart failure with preserved ejection fraction, primary CSA, treatment-emergent CSA) should be informed about the safety signal from the SERVE-HF trial; in some cases the balance of risks and benefits may still favor ASV therapy, particularly in patients who are responding to therapy and have failed prior CPAP.
At the same time, Dr. Badr had the following to say about the results of Serve-HF:
Quote:The results of the current study are applicable only to ASV in patients with HF with reduced EF and should not be extrapolated to other conditions associated with central apnea, nor should they be extrapolated to other therapeutic modalities such as CPAP. Therefore, current recommendations regarding treatment of central apnea are unchanged.2 Initial treatment for central apnea associated with HF should emphasize optimal treatment of heart failure. In fact, it is important to emphasize that CPAP and ASV are fundamentally different modalities. Unlike ASV, CPAP is a pneumatic split and does not provide pressure-support ventilation. CPAP may mitigate post-apneic ventilatory overshoot by increasing lung volumes and decreasing loop gain.11 The majority of patients with central apnea have concomitant obstructive apnea,12 and many others demonstrate upper airway narrowing or occlusion during central apneic events.13 Therefore, a trial of CPAP therapy remains the treatment of choice. However, definitive studies addressing the long-term effectiveness of CPAP in patients with central apnea are still needed. Supplemental oxygen therapy14 is another physiologically appealing intervention; however, desaturation criteria must be met to ensure third-party coverage.
In conclusion, the failure of one modality in a very limited setting does not merit therapeutic nihilism in other settings. Instead, we should continue to use CPAP, BPAP, or ASV where indicated, and be prepared to update our practice as new exciting discoveries illuminate the road ahead.
In summary, I think he and many others would say the following:
1) SERVE-HF provides enough clinical reason to withhold ASV from the great majority of patients with EF < 45% pending further studies. Unfortunately the SERVE-HF results have caused some regulatory agencies to ban similar research. That is likely premature and should be considered in light of SERVE-HF limitations and weaknesses.
2) SERVE-HF provides a safety signal worth of concern and discussion prior to ASV use in patients with normal EF but is not a good reason to withhold ASV treatment from most such patients.
(01-04-2018, 09:42 AM)Sleeprider Wrote: This study has been criticized for a number of variables in terms of treatment efficacy, machine usage and other factors
Similar criticisms can be made about virtually all sleep apnea trials, and the authors addressed those criticisms in the author's reply on this page: http://www.nejm.org/doi/full/10.1056/NEJ...b%3dpubmed
And we should keep in mind that the same variables in machine usage and treatment efficacy are likely to exist in the population of patients for whom this therapy would be prescribed. Plus it goes both ways: just as greater adherence and lesser crossover may have decreased the magnitude of observed mortality risk, it may just as likely have increased the magnitude of observed mortality risk.
Yes, there are weaknesses and limitations, but this was a well done study accepted for publication by the highest impact clinical journal in the world. Most sleep medicine experts consider the findings to be important enough to guide clinical practice in patients with CSA and EF < 45% pending additional study. And just as I have a bit more skepticism for any positive data coming from a drug study funded by the drug maker, I look with a bit less skepticism on negative data coming out of a device trial which was funded in part by ResMed.
When the death rate with low ejection, was 5 times higher than not using one. Those are extreme odds. It really is a big red flag and shouldn't be taken lightly. ASV at this point of time shouldn't be used and no doctor in his right mind would risk his patient, nor open himself up to such a law suit. Ethics wouldn't allow another trial. The results are already known, they are just a bit uncertain as to why. The conciseness is, those with low ejection, should be excluded for their own safety.
I'd watch the whole thing, but this is the statement.
https://youtu.be/Nr08K5IfzzY?t=2137
Prof Simonds comments on the results of the SERVE-HF trial and also discusses the different uses of ASV as therapy for complex sleep apnoea, central sleep apnoea, and opioid-induced sleep disordered breathing. She notes that significant findings have been made regarding the correct usage of ASV, but acknowledges that more work is required in this area.
Ajack, the safety signal is strictly for CHF patients, and the absolute total risk increase was 2.5%. That is 2.5 in 100 or half your claimed 5X risk. This was said to be a 33.5% relative increase in risk according the the Philips Response (http://incenter.medical.philips.com/docl...3D11360660 ) Again, this risk cannot be extrapolated to individuals outside that risk cohort. I will wait for the Reader's Digest version of that 1-1/2 hour video.
Quote: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.
edit to note, in my statistical world a 5X increase is 500% over a control, not 33%. Not disputing the significance and concern, particularly for those with CHF and LVEF<45%. You seem to infer ASV should be not be used on anyone under any circumstances.
(01-04-2018, 03:12 PM)Sleeprider Wrote: Again, this risk cannot be extrapolated to individuals outside that risk cohort.
Again, the risk cannot be definitively extrapolated to individuals outside that group, but it remains to be seen whether individuals outside that cohort may also be at some risk.
Or as Dr. Badr put it:
Quote:Patients who are already using ASV for other indications (eg, heart failure with preserved ejection fraction, primary CSA, treatment-emergent CSA) should be informed about the safety signal from the SERVE-HF trial; in some cases the balance of risks and benefits may still favor ASV therapy, particularly in patients who are responding to therapy and have failed prior CPAP.
He wouldn't advise doctors to inform such patients of the safety signal if we could be 100% sure that it is not relevant to those patients.
Many things in medicine are like that. I treat patients with a medication called exenatide, which causes a rare type of thyroid cancer in rodent studies. Human studies don't show that it causes thyroid cancer in humans, but given a lack of certainty that the rodent data is irrelevant to humans, I inform patients of the animal studies so they can make a fully informed decision.
Part of helping people with normal heart function to make a fully informed decision about ASV is letting them know that it was associated with an increased risk of death in people with a certain type of heart disease and that since we don't know why that was the case, we cannot be certain that it has no risk in other groups.
(01-04-2018, 03:38 PM)Shin Ryoku Wrote:(01-04-2018, 03:12 PM)Sleeprider Wrote: Again, this risk cannot be extrapolated to individuals outside that risk cohort.
Again, the risk cannot be definitively extrapolated to individuals outside that group, but it remains to be seen whether individuals outside that cohort may also be at some risk.
Or as Dr. Badr put it:
Quote:Patients who are already using ASV for other indications (eg, heart failure with preserved ejection fraction, primary CSA, treatment-emergent CSA) should be informed about the safety signal from the SERVE-HF trial; in some cases the balance of risks and benefits may still favor ASV therapy, particularly in patients who are responding to therapy and have failed prior CPAP.
He wouldn't advise doctors to inform such patients of the safety signal if we could be 100% sure that it is not relevant to those patients.
Many things in medicine are like that. I treat patients with a medication called exenatide, which causes a rare type of thyroid cancer in rodent studies. Human studies don't show that it causes thyroid cancer in humans, but given a lack of certainty that the rodent data is irrelevant to humans, I inform patients of the animal studies so they can make a fully informed decision.
Part of helping people with normal heart function to make a fully informed decision about ASV is letting them know that it was associated with an increased risk of death in people with a certain type of heart disease and that since we don't know why that was the case, we cannot be certain that it has no risk in other groups.
So as the patient not having a clue what to do would say "What do you recommend?".
perhaps if you looked at the video and saw the referenced study, you would see the 5 fold death risk of using the asv. It really isn't an option for those with reduced fraction. It really is like russian roulette. It is even worse for those that didn't have defib fitted, the hazard ratio was "astronomic".
FWIW Knowing what I do about the risks on both sides of choosing ASV to treat Apnea where indicated it's needed or not treating via ASV because of the risks due to heart deficiencies, I'd choose treating vs not. This is for me myself only. I'd rather try than not. Why would I say that? If both of my choices meant increased likelihood of death, I'd still try the method that might prolong life. I've lived a long time under the restricting influence of apnea, and a few months feeling better on ASV and getting apnea treated successfully, and I'm certain I'll choose treating via ASV rather than the pathetic "life" I endured beforehand.
Having said that, I'm not choosing for anyone else but me.
Dave
Walla Walla Wrote:So as the patient not having a clue what to do would say "What do you recommend?".
There are all different kinds of patients. Some only care about "What do you recommend" and ignore the rest. Others would rather go without treatment than to take a treatment with a risk, even if that treatment risk is lower than the risk of non-treatment and the doc recommends treatment. And that is their prerogative, IMO.
So if a person with hyperventilation-related CSA and normal EF had a poor outcome with CPAP with or without oxygen (as well as addressing identifiable root causes), I would explain to them the known and possible risks including a discussion of the SERVE-HF safety signal and the possibility that it means there is a related risk involved for them.
In the context of that discussion, I would likely recommend ASV, but I don't think it would be right of me to say that the safety signal was irrelevant to them.
Discounting a 5 fold death risk, where the study was terminated 5 years earlier than planned, because of the ethics and liabilities is strange. I'm certain resemed didn't support this finding for the fun of it. No doctor would suggest a 5 fold risk, when other treatment options are available.
Shin, It may well be that you are who you say you are. Personally I'd prefer the forum admin to either ask for confirmation of being board certified or ask the forum member not to say they are in any way medically qualified. After all this is the internet, where 12 year olds are fighter pilots.
If I recall, one of the comments made in the video was that the problem with the study may have been due to the fact that healthy patients were removed and unhealthy left in the study, hence, the results of ASV looked bad.
Furthermore, I missed the part where they were able to pin point the reason that ASV was causing premature death rate in those with EF of <45%. Without a reasonable explanation, the study is inconclusive, in my opinion.
Healthy patients can use an asv. There is no reason for a healthy person to be concerned. This was looking at a sub group with an ejection factor under 45%. There is no pin point, there was the clinical finding that 5 times the death rate with low ejection. 4 out of 12 in this subgroup died and the trial was cancelled, with the support of the manufacture who funded it. The manufacture then went on to issue a warning to not use their machine for these patients. I don't know if everyone realises the significance of a 5 fold finding. There really isn't any debate at this stage, until further work is done or new treatments for this subgroup are found. They are prescribed the ST mode.
(01-04-2018, 04:41 PM)ajack Wrote: Discounting a 5 fold death risk
The greater than 5 hazard ratio (HR) mentioned in the video refers specifically to patients with EF ≤ 30% without previous hospital admission. This was not part of the original publication but rather the result of a subsequent multistate modeling analysis study meant to help understand the mechanism of the findings from the original publication. The HR for the risks noted in the original study was ~1.3.
We have to be careful about things that come out of the subsequent analyses of a randomized controlled trial (RCT). There's a reason why primary and secondary endpoints are designated at the outset. Otherwise I could take their data set and interrogate it with questions like:
-Was being a Pisces associated with early death with ASV?
-Was being born on a rainy day associated with early death with ASV?
-Was being of German descent associated with early death from ASV?
Surely if I asked enough questions of the data, one would come up with an association with a p value less than 0.05. Such is the nature of chance and is the reason they pick their questions in advance of doing the study.
Now I am not suggesting that the multistate modeling they did was gibberish, throwing stuff against the wall to see what stuck. These are reputable scientists publishing in a very good journal (Lancet Respiratory Medicine), so they must have used legitimate statistical methods. But it isn't the same as designing an RCT with a primary endpoint of cardiovascular death in patients with EF ≤ 30% without previous hospital admission.
-Was being a Pisces associated with early death with ASV?
I'm a Pisces. Could we use a Leo for the example instead please.
I'm a Pisces too, ha
.(01-04-2018, 04:41 PM)ajack Wrote: Shin, It may well be that you are who you say you are. Personally I'd prefer the forum admin to either ask for confirmation of being board certified or ask the forum member not to say they are in any way medically qualified. After all this is the internet, where 12 year olds are fighter pilots.
Let me be very clear that I am NOT a sleep specialist and that nothing I say here should be taken as medical advice. I have changed my signature to reflect that fact. Unfortunately the board software doesn't automatically apply the new signature to all my old posts, and they are beyond the window where I can do so.
I have mentioned that I am a doc here a couple times out of full transparency so that when people are badmouthing docs here and I say otherwise, people can tell where my potential biases lie. Also, I was giving some perspective about how docs may talk to patients.
But I am an endocrinologist (hormone doc), not a sleep specialist. When it comes to sleep apnea, I am a patient, and I am learning here as I go. If anyone wants me to prove that I'm an endocrinologist, feel free to PM me for that. But I'm not going to give medical advice here about my field either.
Sleeprider
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www.ApneaBoard.com
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INFORMATION ON APNEA BOARD FORUMS OR ON APNEABOARD.COM SHOULD NOT BE CONSIDERED AS MEDICAL ADVICE. ALWAYS SEEK THE ADVICE OF A PHYSICIAN BEFORE SEEKING TREATMENT FOR MEDICAL CONDITIONS, INCLUDING SLEEP APNEA. INFORMATION POSTED ON THE APNEA BOARD WEB SITE AND FORUMS ARE PERSONAL OPINION ONLY AND NOT NECESSARILY A STATEMENT OF FACT.
Apnea Board Moderator
www.ApneaBoard.com
____________________________________________
Download OSCAR Software
Soft Cervical Collar
Optimizing Therapy
Organize your OSCAR Charts
Attaching Files
Mask Primer
How To Deal With Equipment Supplier
INFORMATION ON APNEA BOARD FORUMS OR ON APNEABOARD.COM SHOULD NOT BE CONSIDERED AS MEDICAL ADVICE. ALWAYS SEEK THE ADVICE OF A PHYSICIAN BEFORE SEEKING TREATMENT FOR MEDICAL CONDITIONS, INCLUDING SLEEP APNEA. INFORMATION POSTED ON THE APNEA BOARD WEB SITE AND FORUMS ARE PERSONAL OPINION ONLY AND NOT NECESSARILY A STATEMENT OF FACT.
