Glad you can find some hope and optimism, John. I always appreciate your commentary and find it valuable for my clinical practice. You've been incredibly valuable for my ongoing medical learning. way to help my MOC!
One particular patient comes to mind from this study. 55 year old guy whose Apple watch has shown three episodes of AF in the past year. Asymptomatic, each maybe associated with alcohol (he rarely has more than 1 drink, but these all occurred after 2). Each lasting 3-24 hours. Only knew about them because of his watch. Only other co-morbidity is mild hypertension (10mg lisinopril).
He went to see a cardiologist, who started him on apixaban. Due to concerns about bleeding, he's now given up mountain biking and hiking. His wife shared concerns he's getting depressed. He's gained 10lbs in the past 6 months. Also, this medicine costs him over $400/month.
Even based on chadsvasc2 scoring, I don't believe the NNT and ARR/RRR was never there for this guy (given cost/benefit ratio, when you calculate financial and lifestyle cost) and that's assuming he has clinical AF. Their decision though, so I share the calculator data and defer to my patient about if it's worthwhile for them. He was pretty torn on it, the cardiologist had scared the shit outta him about having a stroke - which I'd classify as medical bullying, but that's just one man's opinion.
I suppose my bias steps in as fellow bike rider steps in with this guy (life wouldn't be worth living if I couldn't ride bikes), but as I see it, almost any intervention that lowers exercise tolerance/ability (the most cardioprotective intervention) and diminishes quality of life loses its net benefit (I'm lookin at you, beta blockers and statins).
If this study is “practice changing”, the disturbing part is how that practice even came to be adopted in the first place. There was no evidence for starting OAC (DOAC or otherwise) in pts with AHREs prior to this study, and there remains no evidence for doing so now with these results (at least for episodes up to 3 hours). The unanswered question is at what point (ie duration) of subclinical device-detected AF that benefits of OAC would outweigh risks. In Canada, the guidelines suggest OAC for episodes in excess of 24 hours, but even that is not based on prospective RCT.
It is good to see a well done study that adds to our knowledge….but it also adds to your recurring discussion about therapeutic fashion, whereby treatments become “standard” despite an absence of evidence. Such is the case if one was prone to start OAC for AHRE (esp very short episodes). This trial among many others (like the ones in this series) should serve as yet another wake up call to the cardiology community to not be enthralled by shiny new things, and not just talk the talk about evidence based medicine, but to walk the walk.
Is there a dosage-related compromise regarding anticoagulants?
Why not a moderate prophylactic dose of, say.... Clopidogrel? As an aspirin substitute for the intolerant, surely the balance of harm can be maintained in the patient's favor and adverse events kept to a bare minimum.
I agree that this study addresses and gives some answers to an important question. However, some details were left out. The range of AHR total durations was 0.8-9.2 hours (seems short). What was the total time monitored? Was it 1 month or 1 year? More importantly, it would have been nice if patients were stratified according to AHR duration. If patients with 9 hours of AHRs benefitted more than those with 1 hour from AC, those results could have been hypothesis generating, leading to further studies in patients with higher AF burden.
An active 99 year old patient of mine with a pacemaker was recently observed to have a 2-day episode of AF without Sx. What would you do?
This comment is in the fwiw file. I had a four hour episode of atrial flutter that required a trip to ER and IV metoprolol to slow down. I was sent home with a script for Eliquis and metoprol. Turned out I can't tolerate beta or calcium channel blockers, so, failure of medication. That earned me an atrial ablation. I was 65 at the time.
What surprised me were the side effects of the Eliquis: shortness of breath, fatigue, and over the 3 months it took me to figure out the drug was causing this, a feeling of being slowly crushed to death. I quit the med without consulting my doctors. My electrophysiologist, for whom I have nothing but respect, said he'd never heard of those side effects. I'm not taking any anticoagulant now and have always wondered if I'm being reckless. Seeing this article has helped me feel less like I'm out on a limb. Thanks for this!
Another thought I have is, how many people are out there with a horrible quality of life because they believe these meds are absolutely necessary and they don't connect the side effects to the med?
"Another thought I have is, how many people are out there with a horrible quality of life because they believe these meds are absolutely necessary and they don't connect the side effects to the med?"
Far more than are acknowledged.
One corollary to your speculation is "how many trials are biased because these medications induce fatigue and muscle loss, and the trial participants' physical activity is thereby restricted?"
Both from what I've learned the hard way, and from reading about the commercial research organizations that produce the data for these studies, and those that write them up, I have zero trust in any study run by pharmaceutical companies in collaboration with universities. I think it's pretty unlikely that trial designers would realize side effects of fatigue and muscle loss are confounders. Or admit it.
When people are into their 60s or 70s - still feeling fine and looking forward to a number of good years to come - they can get seriously anxious about AF or about a TIA.
They don't want to 'gamble' with their remaining years. So they are very easy marks for any doctor who swiftly prescribes statins, anticoagulants, or other treatments & interventions.
The idea being sold to these patients is that these treatments will likely prevent strokes, heart problems, and sudden death.
Patients are rarely told that these 'preventive' measures offer just very modest protection at best.
Aren't told that many of them will still have strokes, heart attacks, whatever. And that, unfortunately, many will suffer serious side effects from the treatments - even death, if one can call that a side effect.
And, finally, they usually aren't told that competing causes of death are numerous in old people, so a 'preventive' treatment targeting a single cause may not lengthen a person's healthy life at all.
But, again, old people are easy marks. And the medical industry knows this only too well.
Many thanks Dr. Mandrola for posting. I really like the NOAH study because of the comparison between users and non-users of anticoagulants. Have long looked for real life long-term data on this, but have never found it.
All of these measures are suspect, and the mess they can make of your life, even if they don't kill you, is so little suspected. You really have to become very self-aware and learn also, that not many doctors are critical thinkers.
Thanks for a day of a proper study. As a former neuro/trauma icu nurse I think about patients with embolic stroke going to the cath lab and very often having full recovery after clot retrieval. Risk of bleeding is a complication, increased with age. I also think about people on anticoagulants who go on to develop head bleeds. It is my guess that every proper study will support conservative watching for a stroke that may never happen.
How does one define "a short duration AF"? One minute, one hour, one day, one week,...? Why not do an up-to-date study of all patients, including even those with permanent (subclinical) AF? Perhaps the result shall be the same: no benefit.
Where does that leave patients like me, who (as detected by monitor implant) have a low level of short duration episodes but occasionally have an episode that may last a few days?
First, I'm not a MD, so I'm not qualified to give medical advice. But if I were you, I'd talk to my doctor and ask him/her their opinion on switching to apixaban if you're on something different (links #1 & 2, the drug used in NOAH was edoxaban). Perhaps also inquire about taking it intermittently as needed when experiencing longer episodes (link #3). Good luck!
Thank you for a helpful response. I found the pill in pocket article especially interesting since I've been using pill-in- pocket for reversion with some success but continue to use an anticoagulant on a daily basis. And yes, I'm already on apixaban. I hope we see more definitive studies than those pilots mentioned in the article soon and ideally more data about clotting risk as a function of afib episode duration.
I was surprised the study didn't include apixaban since that appears to be the best - in terms of efficacy/bleeding - of the anticoagulant options. I wonder whether the lowering of the primary end point seen with edoxaban might have reached significance with apixaban which, if combined with less bleeding, might lead to a different conclusion.
Happy it was helpful, and I learned some useful things, too! :) Even if apixaban and edoxaban have equal efficacy in preventing primary endpoints, since apixaban is safer, it may have a positive benefit/risk profile of net benefit. I agree more research is very much needed, especially as more people wear digital external devices that detect afib incidents. All the best!
Glad you can find some hope and optimism, John. I always appreciate your commentary and find it valuable for my clinical practice. You've been incredibly valuable for my ongoing medical learning. way to help my MOC!
One particular patient comes to mind from this study. 55 year old guy whose Apple watch has shown three episodes of AF in the past year. Asymptomatic, each maybe associated with alcohol (he rarely has more than 1 drink, but these all occurred after 2). Each lasting 3-24 hours. Only knew about them because of his watch. Only other co-morbidity is mild hypertension (10mg lisinopril).
He went to see a cardiologist, who started him on apixaban. Due to concerns about bleeding, he's now given up mountain biking and hiking. His wife shared concerns he's getting depressed. He's gained 10lbs in the past 6 months. Also, this medicine costs him over $400/month.
Even based on chadsvasc2 scoring, I don't believe the NNT and ARR/RRR was never there for this guy (given cost/benefit ratio, when you calculate financial and lifestyle cost) and that's assuming he has clinical AF. Their decision though, so I share the calculator data and defer to my patient about if it's worthwhile for them. He was pretty torn on it, the cardiologist had scared the shit outta him about having a stroke - which I'd classify as medical bullying, but that's just one man's opinion.
I suppose my bias steps in as fellow bike rider steps in with this guy (life wouldn't be worth living if I couldn't ride bikes), but as I see it, almost any intervention that lowers exercise tolerance/ability (the most cardioprotective intervention) and diminishes quality of life loses its net benefit (I'm lookin at you, beta blockers and statins).
If this study is “practice changing”, the disturbing part is how that practice even came to be adopted in the first place. There was no evidence for starting OAC (DOAC or otherwise) in pts with AHREs prior to this study, and there remains no evidence for doing so now with these results (at least for episodes up to 3 hours). The unanswered question is at what point (ie duration) of subclinical device-detected AF that benefits of OAC would outweigh risks. In Canada, the guidelines suggest OAC for episodes in excess of 24 hours, but even that is not based on prospective RCT.
It is good to see a well done study that adds to our knowledge….but it also adds to your recurring discussion about therapeutic fashion, whereby treatments become “standard” despite an absence of evidence. Such is the case if one was prone to start OAC for AHRE (esp very short episodes). This trial among many others (like the ones in this series) should serve as yet another wake up call to the cardiology community to not be enthralled by shiny new things, and not just talk the talk about evidence based medicine, but to walk the walk.
Is there a dosage-related compromise regarding anticoagulants?
Why not a moderate prophylactic dose of, say.... Clopidogrel? As an aspirin substitute for the intolerant, surely the balance of harm can be maintained in the patient's favor and adverse events kept to a bare minimum.
Yes, there is. Because bleeding risk is not necessarily linear with dose. So when it comes to bleeding risk, there's no such thing as 'just a whiff'
As an example, bleeding risk is similar on a NOAC and aspirin, but a NOAC has slightly better stroke prevention (see AVERROES trial)
Thank you, that's quite helpful.
I agree that this study addresses and gives some answers to an important question. However, some details were left out. The range of AHR total durations was 0.8-9.2 hours (seems short). What was the total time monitored? Was it 1 month or 1 year? More importantly, it would have been nice if patients were stratified according to AHR duration. If patients with 9 hours of AHRs benefitted more than those with 1 hour from AC, those results could have been hypothesis generating, leading to further studies in patients with higher AF burden.
An active 99 year old patient of mine with a pacemaker was recently observed to have a 2-day episode of AF without Sx. What would you do?
This comment is in the fwiw file. I had a four hour episode of atrial flutter that required a trip to ER and IV metoprolol to slow down. I was sent home with a script for Eliquis and metoprol. Turned out I can't tolerate beta or calcium channel blockers, so, failure of medication. That earned me an atrial ablation. I was 65 at the time.
What surprised me were the side effects of the Eliquis: shortness of breath, fatigue, and over the 3 months it took me to figure out the drug was causing this, a feeling of being slowly crushed to death. I quit the med without consulting my doctors. My electrophysiologist, for whom I have nothing but respect, said he'd never heard of those side effects. I'm not taking any anticoagulant now and have always wondered if I'm being reckless. Seeing this article has helped me feel less like I'm out on a limb. Thanks for this!
Another thought I have is, how many people are out there with a horrible quality of life because they believe these meds are absolutely necessary and they don't connect the side effects to the med?
"Another thought I have is, how many people are out there with a horrible quality of life because they believe these meds are absolutely necessary and they don't connect the side effects to the med?"
Far more than are acknowledged.
One corollary to your speculation is "how many trials are biased because these medications induce fatigue and muscle loss, and the trial participants' physical activity is thereby restricted?"
Both from what I've learned the hard way, and from reading about the commercial research organizations that produce the data for these studies, and those that write them up, I have zero trust in any study run by pharmaceutical companies in collaboration with universities. I think it's pretty unlikely that trial designers would realize side effects of fatigue and muscle loss are confounders. Or admit it.
When people are into their 60s or 70s - still feeling fine and looking forward to a number of good years to come - they can get seriously anxious about AF or about a TIA.
They don't want to 'gamble' with their remaining years. So they are very easy marks for any doctor who swiftly prescribes statins, anticoagulants, or other treatments & interventions.
The idea being sold to these patients is that these treatments will likely prevent strokes, heart problems, and sudden death.
Patients are rarely told that these 'preventive' measures offer just very modest protection at best.
Aren't told that many of them will still have strokes, heart attacks, whatever. And that, unfortunately, many will suffer serious side effects from the treatments - even death, if one can call that a side effect.
And, finally, they usually aren't told that competing causes of death are numerous in old people, so a 'preventive' treatment targeting a single cause may not lengthen a person's healthy life at all.
But, again, old people are easy marks. And the medical industry knows this only too well.
Many thanks Dr. Mandrola for posting. I really like the NOAH study because of the comparison between users and non-users of anticoagulants. Have long looked for real life long-term data on this, but have never found it.
All of these measures are suspect, and the mess they can make of your life, even if they don't kill you, is so little suspected. You really have to become very self-aware and learn also, that not many doctors are critical thinkers.
Thanks for a day of a proper study. As a former neuro/trauma icu nurse I think about patients with embolic stroke going to the cath lab and very often having full recovery after clot retrieval. Risk of bleeding is a complication, increased with age. I also think about people on anticoagulants who go on to develop head bleeds. It is my guess that every proper study will support conservative watching for a stroke that may never happen.
Years ago, when the dinosaurs still roamed, I recall my chief saying “treat the patient, not the finding “. Seems he was right.
Please don't endow "did not reach statistical significance" with any value.
I suspect patients found to have “short” AF when studied using event monitoring post TIA/CVA would still benefit from anticoagulants?
How does one define "a short duration AF"? One minute, one hour, one day, one week,...? Why not do an up-to-date study of all patients, including even those with permanent (subclinical) AF? Perhaps the result shall be the same: no benefit.
Where does that leave patients like me, who (as detected by monitor implant) have a low level of short duration episodes but occasionally have an episode that may last a few days?
First, I'm not a MD, so I'm not qualified to give medical advice. But if I were you, I'd talk to my doctor and ask him/her their opinion on switching to apixaban if you're on something different (links #1 & 2, the drug used in NOAH was edoxaban). Perhaps also inquire about taking it intermittently as needed when experiencing longer episodes (link #3). Good luck!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9767653/#:~:text=Among older patients treated with,compared with dabigatran and rivaroxaban.
https://www.healio.com/news/cardiology/20221101/apixaban-might-be-preferable-to-other-doacs-due-to-lower-gi-bleeding-risk
https://www.tctmd.com/news/anticoagulation-demand-pill-pocket-approach-fib-treatment
Thank you for a helpful response. I found the pill in pocket article especially interesting since I've been using pill-in- pocket for reversion with some success but continue to use an anticoagulant on a daily basis. And yes, I'm already on apixaban. I hope we see more definitive studies than those pilots mentioned in the article soon and ideally more data about clotting risk as a function of afib episode duration.
I was surprised the study didn't include apixaban since that appears to be the best - in terms of efficacy/bleeding - of the anticoagulant options. I wonder whether the lowering of the primary end point seen with edoxaban might have reached significance with apixaban which, if combined with less bleeding, might lead to a different conclusion.
Happy it was helpful, and I learned some useful things, too! :) Even if apixaban and edoxaban have equal efficacy in preventing primary endpoints, since apixaban is safer, it may have a positive benefit/risk profile of net benefit. I agree more research is very much needed, especially as more people wear digital external devices that detect afib incidents. All the best!