As a PCP who doesn’t look at the literature, this is the most directly applicable article I’ve read on SM. Thank you! Easy answer to stop ASA every time I see a patient with both CAD and A-fib.
Asprin and DHA may have a paradoxical interaction that increases thrombotic events. Patients with a stent may be taking more fish oil than other people. ChatGPT helped me come up with this best explanation:
"1. Aspirin acetylation of COX-2 in a DHA-rich milieu alters lipid-mediator balance toward pro-inflammatory or vasoconstrictive species instead of pro-resolving ones.
2. DHA enrichment of platelet membranes modifies thromboxane and isoprostane signaling so aspirin’s antiplatelet effect is functionally blunted or reversed.
3. High DHA oxidation under aspirin’s pro-oxidant conditions generates lipid peroxides that promote endothelial dysfunction and plaque instability.
4. Aspirin-triggered lipid mediator production from DHA competes with EPA-derived resolvins, reducing net anti-inflammatory and anti-thrombotic protection.
5. Combined aspirin + DHA shifts eicosanoid flux away from balanced homeostasis, producing transient hyper-reactivity or rebound thrombosis after platelet turnover."
Fish oil appears to cause AF. But note that that would not be a relevant mechanism here in and of itself, as background fish oil use would be equal. It's the interaction that would matter, with or without AF.
Other suggestions:
Could there be unblinding caused by aspirin use which changes behavior in a deadly way? Feeling protected makes one more lax? Or could aspirin be effective at reducing angina symptoms and a person exerts themselves to death or takes their health less seriously? Promotes silent ischemia?
In the last 10 years of my 40 years of working in Cardiac Rehab, we experienced a huge increase in CAD pts who also had AF prior to their CAD event. Most of them had ASA added to their meds at the time of CAD event. Most had been taking an anticoagulant prior to CAD event. I remember many patients complaining of easy or unexplained bruising. Most of the docs we consulted said the patient would need to stay on both meds. That was 3 years ago. Maybe this trial will improve patient outcomes in our community.
Your summation of “Plausible but wrong” is my favorite line. Without proper studies we never get to the ‘wrong’ Thank you for bringing new information and insight to us all. As a patient and non medical person your work with Sensible Medicine has educated me (even if some of it is over my head :) and helped me be a better advocate for my own healthcare.
As a gastroenterologist in clinical practice for over 30 years, I’ve been summoned to the emergency department and ICU countless nights for patients bleeding on dual anti-thrombotic (DAT) therapy, typically ASA in combination with warfarin or another anticoagulant. I’ve been de-escalating those patients and almost every other patient on DAT I encounter to a single anti-thrombotic, citing the known increased risk of hemorrhage from DAT and the conspicuous lack of demonstrated benefit for most patients. The AQUATIC trial has provided strong evidence this is the right thing to do; thank you for covering it here.
I have ripped into guideline writers increasingly in recent years. But in this case, at least in Canada, the antiplatelet and AF writers were ahead of the curve. We haven’t used combo OAC and ASA for years in those with chronic coronary syndromes and AF.
Can’t exclude that they were right, for the wrong reasons. But their decision to go with the earlier smaller studies proved prescient in this case.
The journals to which I subscribe and which I read,NEJM,Annals,and JCO primarily are crammed with clinical trials designed to suggest a clinical benefit for product X,particularly the latter publication.It is maddening,and fraudulent.Kudos for shedding a tiny bit of light into what seems to be a deepening pool of darkness…
No shocker ... its a testament to the improved anticoagulants -safer.. would ibuprofen be approved today ?
We would send patients home if they did NOT bring in every med in a prescription bottle with their name on it EVERY visit.. you would be amazed... that simple exercise saved more lives than probably anything I have done in my career with the exception of the handful of cases that were more luck than skill.
Question re: “Aspirin is indicated in patients with chronic coronary disease.” I’ve heard arguments that the generally worse clotting that results is a bad trade for the benefits. I’d guess this is likely another situation where the benefits were hyped in the popular media and it led to overprescribing of and even self-medicating with ASA for people who didn’t really need it. Thoughts?
Higher fT4 levels within the reference range were associated with an increased prevalence and incidence of AF. These findings in a large dataset prospectively validate earlier reports and may have important implications, including a redefinition of the normal range and fT4 targets for replacement therapy.
Re K2 MK4, I have found that with K2 MK4, aspirin does not cause bleeding. It can still cause GI problems, but bleeding is not an issue with K2 MK4. It is easy to test on your own body. You take aspirin for 10 or 20 days, and chances are higher you will experience much easier bleeding and bruising. Take 15mg of K2 MK4 for a few days, and it is all gone.
I've coached 80,000 men on health and sex, and I've seen this hundreds of times.
The linked study was retrospective and specified folks who were NOT on thyroid replacement. Yet you’re referencing people being prescribed T4 for low temps? And these people are being prescribed T4 when they don’t need it, and getting AF? Well ok, the last part maybe makes sense. But the people “you know” are extremely strange people.
MK4 “maybe” perhaps has some role to play in bone density but is nowhere near prime time. It has nothing to do with ASA. And why are you taking “ASA for 15-20 days” anyhow?
You sound insane. Get professional help. And maybe a less bizarre cohort of acquaintances. Sheesh.
Yes, let’s launch ad hominem attacks. That’s a great way to argue when you have nothing to argue. People taking aspirin for 15 - 20 days is “insane” to you? Really? What planet are you from, sir?
And you dare to disrespect my anecdotal and self experimentation evidence? On what basis?
One possible contributor to higher thrombotic/ischemic events could be interruption of both drugs during GI or other bleeding events. That should be relatively easy to look at.
As a PCP who doesn’t look at the literature, this is the most directly applicable article I’ve read on SM. Thank you! Easy answer to stop ASA every time I see a patient with both CAD and A-fib.
Dr. John, I have a proposed explanation:
https://pubmed.ncbi.nlm.nih.gov/33964664/
Asprin and DHA may have a paradoxical interaction that increases thrombotic events. Patients with a stent may be taking more fish oil than other people. ChatGPT helped me come up with this best explanation:
"1. Aspirin acetylation of COX-2 in a DHA-rich milieu alters lipid-mediator balance toward pro-inflammatory or vasoconstrictive species instead of pro-resolving ones.
2. DHA enrichment of platelet membranes modifies thromboxane and isoprostane signaling so aspirin’s antiplatelet effect is functionally blunted or reversed.
3. High DHA oxidation under aspirin’s pro-oxidant conditions generates lipid peroxides that promote endothelial dysfunction and plaque instability.
4. Aspirin-triggered lipid mediator production from DHA competes with EPA-derived resolvins, reducing net anti-inflammatory and anti-thrombotic protection.
5. Combined aspirin + DHA shifts eicosanoid flux away from balanced homeostasis, producing transient hyper-reactivity or rebound thrombosis after platelet turnover."
Fish oil appears to cause AF. But note that that would not be a relevant mechanism here in and of itself, as background fish oil use would be equal. It's the interaction that would matter, with or without AF.
Other suggestions:
Could there be unblinding caused by aspirin use which changes behavior in a deadly way? Feeling protected makes one more lax? Or could aspirin be effective at reducing angina symptoms and a person exerts themselves to death or takes their health less seriously? Promotes silent ischemia?
Many patients nowadays are taking large doses of vitamin D. Doesn’t that behavior increase bleeding risk with Anti-coagulation + ASA?
In the last 10 years of my 40 years of working in Cardiac Rehab, we experienced a huge increase in CAD pts who also had AF prior to their CAD event. Most of them had ASA added to their meds at the time of CAD event. Most had been taking an anticoagulant prior to CAD event. I remember many patients complaining of easy or unexplained bruising. Most of the docs we consulted said the patient would need to stay on both meds. That was 3 years ago. Maybe this trial will improve patient outcomes in our community.
Your summation of “Plausible but wrong” is my favorite line. Without proper studies we never get to the ‘wrong’ Thank you for bringing new information and insight to us all. As a patient and non medical person your work with Sensible Medicine has educated me (even if some of it is over my head :) and helped me be a better advocate for my own healthcare.
Thank you for the information. Sharing
As a gastroenterologist in clinical practice for over 30 years, I’ve been summoned to the emergency department and ICU countless nights for patients bleeding on dual anti-thrombotic (DAT) therapy, typically ASA in combination with warfarin or another anticoagulant. I’ve been de-escalating those patients and almost every other patient on DAT I encounter to a single anti-thrombotic, citing the known increased risk of hemorrhage from DAT and the conspicuous lack of demonstrated benefit for most patients. The AQUATIC trial has provided strong evidence this is the right thing to do; thank you for covering it here.
Curious if you had preference for which agent to stop before AQUATIC? Super helpful to know AQUATIC clearly suggests we stop ASA.
I have ripped into guideline writers increasingly in recent years. But in this case, at least in Canada, the antiplatelet and AF writers were ahead of the curve. We haven’t used combo OAC and ASA for years in those with chronic coronary syndromes and AF.
Can’t exclude that they were right, for the wrong reasons. But their decision to go with the earlier smaller studies proved prescient in this case.
Curious if you knew which to stop? Super helpful to know AQUATIC suggests stopping ASA.
The journals to which I subscribe and which I read,NEJM,Annals,and JCO primarily are crammed with clinical trials designed to suggest a clinical benefit for product X,particularly the latter publication.It is maddening,and fraudulent.Kudos for shedding a tiny bit of light into what seems to be a deepening pool of darkness…
No shocker ... its a testament to the improved anticoagulants -safer.. would ibuprofen be approved today ?
We would send patients home if they did NOT bring in every med in a prescription bottle with their name on it EVERY visit.. you would be amazed... that simple exercise saved more lives than probably anything I have done in my career with the exception of the handful of cases that were more luck than skill.
Question re: “Aspirin is indicated in patients with chronic coronary disease.” I’ve heard arguments that the generally worse clotting that results is a bad trade for the benefits. I’d guess this is likely another situation where the benefits were hyped in the popular media and it led to overprescribing of and even self-medicating with ASA for people who didn’t really need it. Thoughts?
Thanks for highlighting this important trial. It confirms what we concluded in a 2020 ACC Consensus document.
https://www.jacc.org/doi/10.1016/j.jacc.2020.09.011
Hopefully AQUATIC will serve as impetus for more APT deprescribing in this group.
Vitamin K2 MK4 is what I take when I take aspirin, and it stops bleeding completely.
AF is iatrogenic usually — the result of giving patients T4 thyroid instead of T4/T3. It has been known for 40 years.
“AF is iatrogenic usually”—-based on what evidence?
Vitamin K stops ASA-induced bleeding? Based on what evidence?
everyone I know with AF has low body temperature, and often they are prescribed T4.
This stuff is not tested, there are few trials, but many breadcrumbs that point to it.
https://onlinelibrary.wiley.com/doi/abs/10.1111/jce.14183
Higher fT4 levels within the reference range were associated with an increased prevalence and incidence of AF. These findings in a large dataset prospectively validate earlier reports and may have important implications, including a redefinition of the normal range and fT4 targets for replacement therapy.
Re K2 MK4, I have found that with K2 MK4, aspirin does not cause bleeding. It can still cause GI problems, but bleeding is not an issue with K2 MK4. It is easy to test on your own body. You take aspirin for 10 or 20 days, and chances are higher you will experience much easier bleeding and bruising. Take 15mg of K2 MK4 for a few days, and it is all gone.
I've coached 80,000 men on health and sex, and I've seen this hundreds of times.
What a complete mess of anecdotal confusion.
The linked study was retrospective and specified folks who were NOT on thyroid replacement. Yet you’re referencing people being prescribed T4 for low temps? And these people are being prescribed T4 when they don’t need it, and getting AF? Well ok, the last part maybe makes sense. But the people “you know” are extremely strange people.
MK4 “maybe” perhaps has some role to play in bone density but is nowhere near prime time. It has nothing to do with ASA. And why are you taking “ASA for 15-20 days” anyhow?
You sound insane. Get professional help. And maybe a less bizarre cohort of acquaintances. Sheesh.
Yes, let’s launch ad hominem attacks. That’s a great way to argue when you have nothing to argue. People taking aspirin for 15 - 20 days is “insane” to you? Really? What planet are you from, sir?
And you dare to disrespect my anecdotal and self experimentation evidence? On what basis?
I’m done with you.
You’re stupid and I told you why. That’s not ad hominem. It’s an observation based on facts in evidence.
Anecdotal evidence is for fools who want to fool themselves.
Btw, I’m from a planet where people don’t take ASA for pain relief. And you seem to be from Planet Moron.
I've reported you and I hope the mods will take care of you.
Strangely - and in contrast to our self-perception that we are practitioners of “modern medicine”-
…we are still blood-letting.
😳
In Sweden (most if not all of us) we stop ASA as soon as anticoagulants are indicated, so it’s assuring to have evidence from a RCT
One possible contributor to higher thrombotic/ischemic events could be interruption of both drugs during GI or other bleeding events. That should be relatively easy to look at.
There are rebound risks with aspirin to boot so that could be. See also my comment on paradoxical interaction between fish oil and aspirin.