Looking for info….

[pellicle]

Frankly, for me, I would find a 0.5 window stressful.

I don't think I could do it.

: rage :

Killing in the name (great cover)

(love spiderman on the kick)

 

[carolinemc]

Hey guys

I’m searching for updated information on INR vs events. I’ll admit that I am terrible at reading chats and graphs and big medical words. I have a Onx valve and have been keeping my INR between 2-3 and my cardio (not my surgeon) wants me to keep it 1.5-2. From the info posted here I believe the data show 2.5-3 is the Sweet spot. But I believe that’s petty old. Any pointers in the right direction would be appreciated.
Scot

I just get relaxed when I am within range, for the people that do my INR/Protime use the same machine as the home devices are. And it is with the cardio for surgeons could care less after surgery is done and we are with the cardio. Mine keeps me at 2.0 to 3.0. I feel comfortable with that range. Not pretty old, just being a safe place. You do not want it at 5.0 or 6.0. for there are dangers with it high, or 1.2 or lower. and it is not hard to maintain, most of the time, 2.0 to 3.0. Been doing it for 21 years and onward.

 

[carolinemc]

Being in the health care industry I have seen much over the last forty years concerning FDA approval and hype from drug/device manufacturers. I was unimpressed with the ON-X data. They concocted a statistic which added bleeding with stoke type issues into a single statistic. So if you don't mind the stroke side of things but are more worried about bleeding than by all means go for a low INR. Personally I am not a big stroke fan. Once something like this gets out and is approved the fine details of what went into the approval are lost in the mist of history. So surgeons get bombarded by detail people about how great their drug/device is and how crummy the other guy's product is. So it is very easy to get swayed by all the bullshit thrown at you. As everyone has said also it is really tough to guarantee that one doesn't go much below 1.5 if the goal is 1.5-2.0. So personally I go for 2.5-3 with my St. Jude. And I would do the same with the ON X if I had one.

The other thing I find amusing is the idea that medical people have all the answers. No one takes a course in using warfarin. Probably in pharmacology is is discussed in a single lecture. Then physicians if they are curious and care about details will read papers when they come out about warfarin and it's use in valve disease. After that they are influenced by what they have done in the past, where they trained, personal bias and the stuff they get fed from the drug/device manufacturers. So ask detailed questions about the use of warfarin from the cardiologists when you are contemplating going for a 1.5-2 INR.
See if you think the answers are founded on good information not just FDA approval.

Mine is handle by professionals in a lab setting and knowledgeable in Warfarin dosing and what to do when it is too high or too low. I have to depend on the them and specialists for medical care. None of my family are medically trained. So it is not wrong to depend on the medical professionals that are trained, but have also have good manners to their patients. And listening to the patient.

 

[Chuck C]

Please see the link below to the PROACT Trial, which was the trial that On-X Life Technologies used to get FDA approval for the 1.5 to 2.0 INR range.

The trial had a test group with a target of 1.5- 2.0 INR and a control group with a target of 2.0 to 3.0 INR.

Here are some data from the trial which you might use to form some questions for your cardiologist:

“The mean INR was 1.89 in the test group and 2.5 in the control group (p < 0.001).”

2.5 is the average INR that we would expect to see in the control group, with a target range of 2.0 to 3.0. However, it is noteworthy that the average INR for the test group, at 1.89, is at the high end of the range for the test group whose target was 1.5 to 2.0. This would be the average that would be expected if the target range was 1.64 to 2.14. Although the 1.89 is within the range of 1.5-2.0, it would appear that the guidance for warfarin management was possibly staying as far away from the 1.5 threshold as possible.

I would print a copy of the PROACT Trian and bring it to your next consult. Ask your cardiologist if he doesn’t think that it makes more sense to have a target of about 1.7 to 2.2, which would be more consistent with an average INR of about 1.9, which the test group had.

The rate of TE and thrombosis events was 60% higher for the test group with the lower INR. The study authors dismiss this. In fact, their choice of wording is troubling to me:

“…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)”

Their statement is factually incorrect. There are not “no differences”. They could make the argument that the difference is “not significant”, but they can’t say that it is the same. Take a look at figure 3 from the study and you will see that the longer the time goes out, the bigger the difference in TE and thrombosis is between the test group and the control group. They are not the same. The test group had 60% more TE and thrombosis events.

While 2.96% might seem like a low event number in relative terms, remember this is in patient years. When one takes this out a decade, the numbers become more striking: 29.6% TE and thrombosis events for the test group vs 18.5% for the control group.

So, I would ask your cardiologist if he believes that a 10 year TE and thrombosis rate of 29.6% is acceptable.

Another point which should be made. The pre-surgery figures indicate that there were 3x as many afib patients in the control group as compared to the test group. See quote below from the study. As afib is a major cause of TE and thrombosis, this would suggest that, everything else being equal, we would expect to have more TE and thrombosis events in the control group, which makes the figure of 60% more events in the test group all the more striking.

“The two groups were comparable in terms of patient demographics, except for a marginally higher prevalence of preoperative atrial fibrillation in the control group (6% versus 2%, p = 0.06”

Ultimately I would summarize as follows:

Is the trade off of having 60% more TE and thrombosis (stroke and heart attack) events worth it to lower the risk of having bleeding events? Keep in mind that the vast majority of bleeding events are resolved.

Given that the average INR for the test group was about 1.9, near the high end of the INR target range, does it really make sense to bring the low end of the target range all the way down to 1.5? It would appear to me from the data that the guidance likely steered clear from that line. Just looking at the trial data, even if one accepts that getting 60% more TE and thrombosis is a good exchange for a lower risk of bleeds, isn't a slightly higher INR target reasonable?

The PROACT Trial

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472691/

 

[ottagal]

Speaking of On-X, did anyone see this latest clinical trial?

I have no comments as I have a tissue valve (SVD..monitored - severe stenosis) and am just sharing as a FYI....
PROACT Xa - A Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely on Apixaban - Tabular View - ClinicalTrials.gov

A Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely on Apixaban

 

[pellicle]

Speaking of On-X, did anyone see this latest clinical trial?

Yes, looks interesting, may also be relevant to other valves. Speaking for myself I'd probably stick with the devil I know because warfarin and self testing will still be cheaper.

 

[ottagal]

Yes, looks interesting, may also be relevant to other valves. Speaking for myself I'd probably stick with the devil I know because warfarin and self testing will still be cheaper.

I think I would feel the same if I had experience knowing how to manage warfarin. If you have had a good track record historically ,why change it?

 

[vitdoc]

Few points to make about the apixaban study. One it requires a twice a day dosing. Two it requires aspirin also. In the real world where people forget their meds the anticoagulation status of someone on apixaban might flucuate more rapidly than on warfarin if they miss a dose. In the study the patients will be encouraged to be accurate with their dosing. We shall all await the results.

 

[ottagal]

Few points to make about the apixaban study. One it requires a twice a day dosing. Two it requires aspirin also. In the real world where people forget their meds the anticoagulation status of someone on apixaban might flucuate more rapidly than on warfarin if they miss a dose. In the study the patients will be encouraged to be accurate with their dosing. We shall all await the results.

Excellent points. Compliance could be problematic especially with 2 doses a day and ASA.

 

[pellicle]

Good morning and happy easter to all

. In the real world where people forget their meds the anticoagulation status of someone on apixaban might flucuate more rapidly than on warfarin if they miss a dose.

its an interesting point and I happened to look up the reversal procedure for Apixaban last night (as a result of the post by @ottagal ) and found only that administration of activated charcoal was suggested if the previous dose was had less than 2 hours prior.

Because its a direct anticoagulant you can't simply kick start coagulation with a well known, tried and tested administration of Vitamin K in an ER situation.

 

[pellicle]

if I had experience knowing how to manage warfarin.

while you may not now, there are people who are helpful in sharing that experience here.



Best Wishes

 

[ottagal]

while you may not now, there are people who are helpful in sharing that experience here.



Best Wishes

Thank you and I will most certainly take you and others up on your expertise, when/if the time comes! It is reassuring to know I can rely on others such as yourself with the expertise and personal experience...invaluable....

 

[Superman]

Good post and link, Chuck. That trial should probably be a sticky at the top of the valve decision or anti-coagulation threads. Only part I’ll disagree with is this comment:

While 2.96% might seem like a low event number in relative terms, remember this is in patient years. When one takes this out a decade, the numbers become more striking: 29.6% TE and thrombosis events for the test group vs 18.5% for the control group.

These types of statistics aren’t cumulative like that. Almost 32 years in and I have the same odds for an event as when I started. I’m not up to 60% now. Thank goodness!

I found it interesting that the odds of a mortality related event overall are about equal (ever so slightly higher for the test group). It’s just a matter of picking your poison. Do you want a stroke? Or a bleeding event? Choose your preference and we’ll set your range. I feel like the On-X study makes people choose a stroke.

Fortunately for either, for the overwhelming majority with a well managed INR nothing happens anyway. But still. For me, erring on the high side with downside cushion passes my sleep at night rest.

 

[Chuck C]

These types of statistics aren’t cumulative like that. Almost 32 years in and I have the same odds for an event as when I started. I’m not up to 60% now. Thank goodness!

Hi Superman.
Yes, I know that these statistics are not cumulative. Perhaps I should have worded it better. What I mean is that this would be the approximate odds looking forward over the next 10 years. For example 10 x 2.96% = 29.6%. So, that would be the risk over the course of the coming decade. It would not mean that on year 11 the odds of a stroke would be 29.6%. KInd of like Russian Roulette. Each time you play the game, odds are 1/6 that you get the bullet. But, if you plan to play it 10 times in a row, the odds are pretty high that you will take a bullet in the coming 10 rounds. Still, if you are lucky and make it to the 10th trigger pull, the odds will still be 1/6 fo that next trigger pull will have the bullet.

I found it interesting that the odds of a mortality related event overall are about equal (ever so slightly higher for the test group). It’s just a matter of picking your poison. Do you want a stroke? Or a bleeding event? Choose your preference and we’ll set your range. I feel like the On-X study makes people choose a stroke.

Yes good point.

Also, one thing to consider. Just because they mortality from all causes are about equal does not make the two ranges equal. As demostrated from these statistics, most people survive these events, whether one is the low test group or the standard range. I would expect that it would be much better to be a survivor of a bleeding event, than a survivor of a stroke. Many of the stroke and heart attack survivors will carry with them permanent damage.