400 person study on lower INR (1.5-2.5) with mechanical valve

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djman

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Study began in late 2019 and results are supposed to be available by the end of 2022.
But IMO these studies are problematic. People in this clinical study are closely monitored and they get better quality INR management than what often happens out in the wild. Hence these studies are not really representative of the general population.
 

Chuck C

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But IMO these studies are problematic. People in this clinical study are closely monitored and they get better quality INR management than what often happens out in the wild. Hence these studies are not really representative of the general population.

You're spot on. The trial participants will be much more closely monitored than the average person on warfarin.
 

AZATADINE

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This may be a bit of a stupid question but what exactly is the big attraction of a lower INR anyway? I was on warfarin for three months post op and my range was 1.8 to 2.5 but I never really felt all that comfortable when I was around the 1.8. I was always more comfortable around the 2.5 and I didn't mind if I went a bit over but I never liked to be under the 1 8. My valve is tissue so its not the same I know but still....I'd always be a bit iffy about being on the lower side of the range, especially with mechanical?
 

Superman

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Here’s my thinking after 32 years. If it’s anything like the Proact study, it seems to depend on where one is comfortable with their negative event occurring. On the bleeding side, or on the clotting side. Because it appears to me that in the end, the negatives about average out and are likely more related to mismanagement or an unforeseen patient response to Warfarin that just makes it not work for them, rather than any inherent issue with any particular range.
 

pellicle

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But IMO these studies are problematic. People in this clinical study are closely monitored and they get better quality INR management than what often happens out in the wild
Leaves one asking why the real world does not catch up best practice. Diabetic patients are monitoring more, not less. Everything is going fingerstick and embracing the electronic systems. Except INR management, where a clinic that focuses on vein draws, promotes extending out the testing rate to more than a week (makes sense btw with respect to vein injury) and doesn't really care as much about you as their liability is the norm.

PS: this is a segment from Dr Schaff's presentation on valves and coagulation, I feel its still the case 15 years later on

 
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pellicle

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This may be a bit of a stupid question but what exactly is the big attraction of a lower INR anyway?
If one engages in a contact sport or activities where falls can happen, an IC bleed will harm you more.

Not everyone on ACT is a doddering elderly person (admittedly it's a minority).
 

AZATADINE

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If one engages in a contact sport or activities where falls can happen, an IC bleed will harm you more.

Not everyone on ACT is a doddering elderly person (admittedly it's a minority).

Sure, I understand that but it's not like as if the existing INR range is that high to start with though - is it? I dunno, I'd be reticent to go near an INR of 1.5 on a mechanical valve though.
 

pellicle

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ure, I understand that but it's not like as if the existing INR range is that high to start with though - is it?
its not my personal view that it is too high. My personal view is that I am very comfortable between 2.0 ~ 3.0

To me there seems almost some sort of paranoia or anxiety on this issue which is (in my view) driven in part by the unconscious anxiety promoted by the (probably ill informed) medical patients (which is likely focused on the majority of warfarin users who are stroke sufferers).
 

pellicle

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oh, in case you've already read my above post I wanted to add a quick PS:

It is also my view that these studies are too short term and do not encompass the effects of longer term problems assoicated with lower INR levels, these are not commonly the thing that everyone is frantic about (namely thromboemolic stroke) but are problems none the less. One such issue is obstructive thrombosis. This has driven reoperation.

1651696448105.png


this takes perhaps years to develop. People seem to obsess about the now and forget what may happen in 5 or 10 years.

So for myself I'll manage my INR down for specific needs and remain target = 2.5 for daily life.
 

pellicle

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I'd be the same - target = 2.5.
I think that the desire to publish and to do new research (driven in part by the last 20 year trend of "Publish or Perish" within Universities) and the existing (now out of context) view that higher INR is a problem.

First "higher than what" as high is relative to something, its qualitative not quantitative. Quite an amount of research has been done on INR levels already and the known data is pretty clear, yet still there is an agitation within the medical community about the dangers of warfarin therapy (I'm not going to suggest that the drug companies want more money than they make from warfarin, that would be unseeming).

The elephant in this INR (panic) room is management and Time in Therapeutic Range. TTR is well associated with minimisation of harm, yet its seldom called out as being the keystone it is. Far too many studies are based on 70% TTR (or lower), yet I would say that among the self managers here (probably even the self testers) that they get more like 90% TTR.

Thus I believe that the exsisting guidelines are actually optimal. Eg

European Heart Journal (2021) 00, 172
doi:10.1093/eurheartj/ehab395
2021 ESC/EACTS Guidelines for the management of valvular heart disease
1651702346758.png

to me all the agitation is only for the agitated (or panic striken) who are misled into thinking that there is some monster under the bed (or the marketing division of the smaller newer valve companies wanting to get presence).
 
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Keithl

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I thought the existing stats are pretty compelling the 2-3 is the best range and then 2.5-3 being the sweet spot. Not sure what they see in 400 people will sway me form my 2-3 range with my target being 2.5-3.
 

PeterII

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"For me" with an Onx since 2015 the 1.5 -2 range is something i did try during first year but i was always worry about it going below 1.5, so ever since 2017 i have been using 2 - 2.5, my ideal number is 2, that is what works best "for me"'; do not see the need to play with below 2 numbers, it was stressful and something else to worry about , with the 2.0 - 2.5 i dont even think of warfarin as a problematic thing.
 

Keithl

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I also have the On-x and my surgeon said 1.5-20 ad I and my cardio said 2-3 which is what I shoot for and it works out as I have had some swings from low 2's to low 3' so thinking that 1.5-2.0 could drop to 1 would scare me too much.
 

RAS

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Everything is going fingerstick and embracing the electronic systems. Except INR management, where a clinic that focuses on vein draws


I'm curious what regions/countries still do venous draws for routine INR management? My experience has always been that clinics use finger sticks.

After my AVR, I went to a coumadin clinic for about a year before switching to home testing. They always used a finger stick and portable device. That was 16 years ago. Since then, occasionally, I had my INR tested at several different clinics. They all used a Coaguchek device.

The only times, I had INR tested via lab was when I specifically asked for it to be added as part of my annual physical where they were drawing blood anyway for lipid and other typical tests as part of the physical.
 

Chuck C

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"For me" with an Onx since 2015 the 1.5 -2 range is something i did try during first year but i was always worry about it going below 1.5, so ever since 2017 i have been using 2 - 2.5, my ideal number is 2, that is what works best "for me"'; do not see the need to play with below 2 numbers, it was stressful and something else to worry about , with the 2.0 - 2.5 i dont even think of warfarin as a problematic thing.

I think that you are wise to stay above 2.0. The study that is underway references the two previous studies which looked at lower INR range, the Proact Trial and Lowering It. Proact targeted 1.5-2.0, but there was tight INR control and the average INR for the test group was 1.89, actually very close to the 2.0 mark. This suggests to me that they were cautious to stay away from the 1.5 threshold. Lowering It, which had a target range of 1.5-2.5 for the test group had an average INR of 1.94. So, both of these trials had tight control and even though there was a low threshold of 1.5, it would appear that they probably steered clear of that. It is one thing to test weekdly and have the A Team working coagulation management. In the real world, many go 4-6 weeks between INR testing and they don't always have the A Team coagulation management in play, making it even more precarious.

These studies all play games with words as well, I have noticed. They will lump all bleeds together, not separating major bleeds from minor bleeds. Then then will say, the lower INR resulted in fewer bleeding events with no increases in strokes or heart attacks. But, when you look at the actual results you find that Lowering IT had 3x as many thrombolic events in the test group as compared to the control group. How then are they able to say that the stroke events were "similar" or the same? It is because due to relatively small numbers of participants and relatively short period of study, the number of thrombolic events was 3 for the test group and 1 for the control group. It is new math to say that there was no difference, but apparently they get a pass because the two are both relatively low numbers. Increase the number of participants by 10 fold and take the study out 20 years and they will not be able to say that there was no statisical differnce when the number is something like 100 thrombolic events vs 300.

" Two moderately-sized clinical studies showed that an INR target range of 1.5-2.5 resulted in less bleeding than the usual higher target range without increasing blood clot formation or stroke in patients with a newer valve model. "

Is this true? Not really. Lowering It found 3x as many thromboembolic events in the test group with the lower INR.

" One versus three thromboembolic events occurred in the LOW-INR and CONVENTIONAL-INR, respectively, .."


Look at how Proact uses new math to claim that a 60% increase in TE and thrombosis is "no different'

“…with no differences in the rates of TE and thrombosis events (2.96%/pt-yr in the test group versus 1.85%/pt-yr in the standard group, p = 0.178)”

The Prospective Randomized On-X Valve Anticoagulation Clinical Trial (PROACT): Lower is better, but is it good enough?

So, then in the new study, given the mathematical slight of hand, when referencing the two studies, they claim:

"..without increasing clot formation or stroke.."

Each have to make their own decision with the consultation of their medical team, but I would give some margin away from the 1.5 INR line.

Both studies found fewer bleeds in the lower INR group, but more strokes and heart attacks. Why not stick to the INR ranges that have the lowest events of all? Personally, I'd rather have a bleeding event than a stroke. That being said, some patients, who have issues with bleeding or are more prone to bleeding, might find that the trade off is worth it. I believe that these studies are valuable and give us important data. But, what I find troubling is that there appears to be bias in the presentation of the data favoring the sponsor of the studies economic interest in suggesting a lower INR is better. And, to be clear, the FDA in approving the lower INR for On-X, is not saying the lower INR is better. They just found that the number of events in that lower range to be reasonable.
 
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Chuck C

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I'm curious what regions/countries still do venous draws for routine INR management? My experience has always been that clinics use finger sticks.

I home test. But the testing done before I home tested and the occasional test to check the accuracy of my Coaguchek was done via venous draw at the lab. It may be the if you go directly to the coumadin clinic for the test that the finger prick may be more common.

It will be interesting to see what the experience is of others on this.
 

carolinemc

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I thought the existing stats are pretty compelling the 2-3 is the best range and then 2.5-3 being the sweet spot. Not sure what they see in 400 people will sway me form my 2-3 range with my target being 2.5-3.
These studies are on the small scale and it would take many, many more the make a change. I would not risk going by one small study to agree to a change.
 
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