CryoLife On-X INR Claims

[tom in MO]

I make it a personal habit to only assert things which are supportable with robust theory, data or sufficient evidence. I do realise that such is not fashionable

You make it a personal habit to assert that a higher INR is better than a lower one no matter what "Science" in the form of the valve manufacturer and cardiologist say. Your belief in a higher than recommended INR is a personal risk assessment, not based upon empirical data but what "feels good in your gut." I stick to my recommended range of 2-2.5 based upon empirical data and risk assessment done by professional statisticians, cardiologists and medical device engineers.

 

[Chuck C]

You make it a personal habit to assert that a higher INR is better than a lower one no matter what "Science" in the form of the valve manufacturer and cardiologist say. Your belief in a higher than recommended INR is a personal risk assessment, not based upon empirical data but what "feels good in your gut." I stick to my recommended range of 2-2.5 based upon empirical data and risk assessment done by professional statisticians, cardiologists and medical device engineers.

Pellicle has done a better job of providing supporting data for his INR position than anyone else on this forum. It is not even close. Rather than attack him personally, why don't you provide supporting evidence if you have a different view than his regarding the appropriate INR range?

 

[pellicle]

Your belief in a higher than recommended INR is a personal risk assessment, not based upon empirical data but what "feels good in your gut."

you really are blind aren't you Mr Selective Reader

good in my gut ... what a pathetic attempt.

I regularly cite this scientific study
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/415179

"Optimal level of oral anticoagulant therapy for the prevention of arterial thrombosis in patients with mechanical heart valve prostheses, atrial fibrillation, or myocardial infarction: a prospective study of 4202 patients."​

(bold mine, in case you missed that)

... meanwhile when challenged you regularly cite "nothing" or "personal communications with your cardio".

I look forward to your empirical data that contradicts this graph from that study

So if either of us is talking out of our arse mate, its you...

 

[pellicle]

Hey Chuck, thanks for the shoulder tap.

Rather than attack him personally, why don't you provide supporting evidence if you have a different view than his regarding the appropriate INR range?

because he doesn't have any

 

[Critter]

I am also monitoring and keeping my INR at 2.0 . Any thinner than that and I start having some anal/rectal bleeding from poop. I am taking advantage of the technology of carbon fiber making the leaflets as slick as ice. Plus when you take the 81mg asa it adds a 40%decrease in thrombosis than with warfarin alone. My life is about science so I gotta go with the science of having my INR lower. As always your mileage may vary.
With the Onyx doing a study with factor 10A inhibitor solely tells you how “slick” the valve is.

 

[pellicle]

My life is about science so I gotta go with the science of having my INR lower. As always your mileage may vary.

and indeed using your own personal evidence (assuming its properly gathered) is very significant. Guidelines are for the statistical norm, not only for the individual.
We are fortunate that studies show us that we don't need to worry unduly if we are around INR=2 with modern bileaflet pyrolytic carbon valves. If we have a good reason to be outside the "standards" then we should follow those reasons (and understand the other risks).

Life is about risks, certainty lays in death.

PS: @Critter did you see this post?
https://www.valvereplacement.org/threads/how-long-can-you-go-without-it.887951/

 

[MdaPA]

I am also monitoring and keeping my INR at 2.0 . Any thinner than that and I start having some anal/rectal bleeding from poop.

So does this mean that you have some bleeding disorder or injury down below?...i.e. it shouldn't cause you to just start bleeding, should it?

 

[pellicle]

So does this mean that you have some bleeding disorder or injury down below?...i.e. it shouldn't cause you to just start bleeding, should it?

as a guess yes (because no), I suspect diverticulitis, but I didn't want to probe...

oops, don't touch that ;-)

 

[Critter]

I had a colon/egd 1 week prior to AVR to get everything checked by my physician. I had some constipative symptoms prior to surgery, these have improved greatly since surgery 6 months ago. I do not have a bleeding disorder or some weird factor disease. Yes it presents commonly in a primary care office but when investigated with colonoscopy it is usually due to internal hemorrhoids or increased vascularity in the rectal vault. It’s common

 

[Keithl]

You make it a personal habit to assert that a higher INR is better than a lower one no matter what "Science" in the form of the valve manufacturer and cardiologist say. Your belief in a higher than recommended INR is a personal risk assessment, not based upon empirical data but what "feels good in your gut." I stick to my recommended range of 2-2.5 based upon empirical data and risk assessment done by professional statisticians, cardiologists and medical device engineers.

I leverage multiple sources and from what I see the On-X research was a very limited statistical base. I will go with the 30+ years of mechanical valve data where 2.5-3.0 is the lowest risk, f the On-X provides a better design to help drive the events down more then great, but with swing of .5-.7 the last 2.5 years trying to stay within 1.5-2.0 is too much work. My range is very consistently in a 2.5-3.1 with occasional swing to 2.3 and 3.4, all those are in a range that I am comfortable with. Trying to do that in a 1.5-20 range would be too much work.

 

[vitdoc]

The problem with the On-X data was that it was not very robust. It was a small trial of less than 100 participants. If one looked at the data there was a higher risk of thromboembolic events and a lower risk of bleeding. The company concocted a combo statistic combining these two different issues to present to the FDA.
As I mentioned earlier I have been losing faith in the FDA making good medical decisions. I don't think from what I saw that the low INR that On-X recommended should have been authorized by the FDA based on the data. The bottom line was if you are willing to tolerate more thromboembolism go for the low INR.
Personally I am not a fan of strokes. I would much more take my chance of bleeding which is not much different at 2.5 from 2 than a stroke.
Also as has been mentioned many times if you aim for 2 you frequently may be at 1.something. Strokes are not very fixable. Over the years I have had several retinal artery occlusions which where fortunately transient. These occurred before I was testing my INR more frequently. They were very frightening seeing half your vision in one eye disappear. And I am a retinal surgeon. So the gain from maintaining a low INR to me is much riskier than say 2.5-3.5.

 

[Keithl]

The problem with the On-X data was that it was not very robust. It was a small trial of less than 100 participants. If one looked at the data there was a higher risk of thromboembolic events and a lower risk of bleeding. The company concocted a combo statistic combining these two different issues to present to the FDA.
As I mentioned earlier I have been losing faith in the FDA making good medical decisions. I don't think from what I saw that the low INR that On-X recommended should have been authorized by the FDA based on the data. The bottom line was if you are willing to tolerate more thromboembolism go for the low INR.
Personally I am not a fan of strokes. I would much more take my chance of bleeding which is not much different at 2.5 from 2 than a stroke.
Also as has been mentioned many times if you aim for 2 you frequently may be at 1.something. Strokes are not very fixable. Over the years I have had several retinal artery occlusions which where fortunately transient. These occurred before I was testing my INR more frequently. They were very frightening seeing half your vision in one eye disappear. And I am a retinal surgeon. So the gain from maintaining a low INR to me is much riskier than say 2.5-3.5.

This issue alone has made me lose faith in the FDA. And I thought it was a 1000 and I thought that was too small, if it was 100 then that is a joke.

 

[BillDaThrill]

As of late July, On-X had enrolled 360 folks in the current PROACT study - they are aiming to enroll 1000.
Per their latest earnings call (it is all about the money, right?), Cryolife (On-X parent company) reported: We continue to make significant progress on the enrollment of our PROACT Xa trial. Our prospective randomized clinical trial determine if patients with On-X aortic valve can be maintained safely and effectively on Eliquis versus warfarin. We currently have enrolled 360 patients in this study. Feedback from surgeons and patients participating in this trial remains very positive. Despite pandemic headwinds and assuming the trial meets its endpoints, we believe we can still achieve FDA approval for this new indication by late 24 or early 25.
My surgeon, Dr. Lars Svensson (Cleveland Clinic), co-chairs the steering committee on the study and was very positive on the results (to date) when I spoke with him prior to my surgery (early June).
Just reporting - have no opinion of the no or lower warfarin approach as I'm a newbie to by mechanical valve. So far, keeping my INR between 2-3 (Cleveland Clinic range for the On-X) has been real easy and don't notice any day-to-day impacts. Am happy to be ticking!

 

[Chuck C]

So far, keeping my INR between 2-3 (Cleveland Clinic range for the On-X)

I think that keeping the On-X in the range of 2-3 is good. Interesting that Cleveland Clinic, who probably does more On-X valves than anyone, apparently scraps the manufacturers recommendation of 1.5-2.5 and goes with the range that the data from the last 30 years for a mechanical valve in the aortic position, 2-3. My second consult with Dr. Shemin at UCLA was to discuss whether I would go with a St Jude or On-X. He gave me his thoughts on each and indicated it was my choice. But, he said that if I choose the On-X, he is not ok with the range being 1.5-2.5 and that it will be 2-3. He indicated that he and his colleagues are not at all convinced with the data from the study supporting letting INR go down to 1.5.

We have had at least 2 participants on this forum(I am prettey sure that there have been more) share their devastating experience in using a low end range of 1.5 INR. When looking at the data as to where events occur, there are very few events occuring from 2.5-3.0. So, when adopting a lower range of 1.5-2.5 and disregarding the 2.0-3.0 range, you are disregarding the range of 2.5-3.0 and replacing that portion of the range with 1.5-2.0. The question is, given that the vast majority of bleeds are occuring at INR 5.0+, and very very few are occuring at 2.5-3.0, and given that many more strokes happen in the 1.5-2.0 range, from the historical data, what is to be gained from this trade off?

What is missing in the data from that small trial is the actual INR values from the patients who suffered events. It found more strokes in the 1.5-2.5 experimental group. It found more bleeds in the 2.0-3.0 group. But, what were the INR values? If the bleeds are happening at 5.0+ INR, and not in the 2.5-3.0 range, then the issue is more a matter of INR management. Without the detailed INR data, I can't see how this study is of any use.

In any case, it sounds like most of the people on the forum who have an On-X are using 2.0 as the low end of their range. In my view this is the cautious approach and I'm glad to hear that this is the policy of Cleveland Clinic, as it also appears to be the policy of UCLA, at least from my experience in discussions with my surgeon and cardiologist.

 

[BillDaThrill]

Yeah, well, ummm, for full disclosure - as I understand it, Cleveland Clinic asks On-X'ers to maintain an INR of 2-3 for the first 3-6 months (going off memory), then goes with the recommendation of 1.5-2.5 (which, I believe, is consistent with the Cryolife position). I hit my 3 month date tomorrow but have no plans to drop from the INR range of 2-3. Have yet to receive any updates from Cleveland (just a single phone call from a nurse to see how I was recovering) - and since I am under the care of a local cardiologist now - perhaps I won't receive any new lower INR guidance. But yes, I agree with what you are saying Chuck C, there is a lot more to consider than simply 'lower INR = less bleeds'.

 

[tom in MO]

you really are blind aren't you Mr Selective Reader

good in my gut ... what a pathetic attempt.

I regularly cite this scientific study
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/415179

"Optimal level of oral anticoagulant therapy for the prevention of arterial thrombosis in patients with mechanical heart valve prostheses, atrial fibrillation, or myocardial infarction: a prospective study of 4202 patients."​

(bold mine, in case you missed that)

... meanwhile when challenged you regularly cite "nothing" or "personal communications with your cardio".

I look forward to your empirical data that contradicts this graph from that study

So if either of us is talking out of our arse mate, its you...

Your cited study is 12 years past publication, thus the information is close to 15 years old. Outdated information, I know my St. Jude went from a range of 2-3 to 2-2.5 close to 10 years ago. "I look forward to your empirical data" as well

Only reference needed by some would be the Cleveland Clinic (esteemed by many on this forum) says 1.5-2 is Ok for the On-X

as a guess yes (because no), I suspect diverticulitis, but I didn't want to probe...

oops, don't touch that ;-)

You guess diverticulitis which can be fatal if not treated and certainly has other symptoms, which if not present, easily rule out diverticulitis. I know, I lost 6" of my colon to it. The most common cause of blood in one's stool is a hemorrhoid, a common problem easily mitigated. Your response should not have been an off-the-cuff remark guessing a disease as a cause, you should have told the person to see a doctor.

 

[pellicle]

Hey Bill

As of late July, On-X had enrolled 360 folks in the current PROACT study - they are aiming to enroll 1000.

and that's the point ... with statistics its a numbers game and of course will not identify the problems with the outliers. The outliers may be of no consequence, however if it is you then you'll perhaps feel like this person:

https://www.valvereplacement.org/threads/failure-of-onx-valve-and-problems-with-lowering-inr.878615/
the thread is poorly named but the issue she had is related to her being an outlier statistically speaking.

Its also important that if you are going to follow the protocol that you need to be doing what they did (or you may get different results).

So from
https://clinicaltrials.gov/ct2/show/NCT00291525
Let me highlight a few key points:

Detailed Description:​

This is a longitudinal, randomized (randomization to occur at the 3-month follow-up) study comparing the On-X valve on low dose anticoagulation (test group) to concomitant control groups of On-X valves receiving standard Coumadin/aspirin therapy, and also to FDA objective performance criteria (OPC) for heart valve replacement. It is a multicenter study consisting of up to 50 centers in the United States, Canada, and Italy enrolling and randomizing no more than 1200 patients (200 in each of 6 groups). There are three test arms of the study: low risk aortic valve replacement, high risk aortic valve replacement, and mitral valve replacement. Each arm has an equivalent control. Test therapies are: low risk aortic valve replacement - aspirin/Plavix, high risk aortic valve replacement - Coumadin at INR of 1.5 to 2.0 plus aspirin, and mitral valve replacement - Coumadin at an INR of 2.0 to 2.5 plus aspirin. Follow-up will run for up to 8 years in each patient. Each arm is independent and the low risk aortic and high risk aortic arms are completed. The low risk aortic arm was closed early resulting in a reduction of the estimated total enrollment with randomization to 1000. The high risk arm is completed with FDA review and this arm had 375 randomized enrollees. The mitral arm continues to enroll with a planned randomized enrollment of 400.​

INR was sampled weekly IIRC

So if you arent doing

• weekly testing (and concomitant adjustment of dose if needed)
• taking aspirin at the same time

you aren't following their study.

As we know that's not a large patient selection, and so running a study with 500 people for 5 years is not quite the same as running 4000 patients for 1.6 years.

The results details are also worth reading too ... I believe that aspirin / plavix arm of the trial was halted.

 

[Chuck C]

Yeah, well, ummm, for full disclosure - as I understand it, Cleveland Clinic asks On-X'ers to maintain an INR of 2-3 for the first 3-6 months (going off memory), then goes with the recommendation of 1.5-2.5 (which, I believe, is consistent with the Cryolife position). I hit my 3 month date tomorrow but have no plans to drop from the INR range of 2-3. Have yet to receive any updates from Cleveland (just a single phone call from a nurse to see how I was recovering) - and since I am under the care of a local cardiologist now - perhaps I won't receive any new lower INR guidance. But yes, I agree with what you are saying Chuck C, there is a lot more to consider than simply 'lower INR = less bleeds'.

Thanks for the clarificaiton Bill.

Also, just 3 weeks ago, earlier in this thread:

" Wondering if anyone else has had a heart attack from a blood clot while on INR protocol of 1.5-2. or other blots, stroke? Had valve replaced in 2017, had heart attack in 2019 due to blood clot blocking 100% of my LAD, aka widow maker. "

https://www.valvereplacement.org/threads/cryolife-on-x-inr-claims.888035/#post-909904

 

[user 16827]

I stick to my recommended range of 2-2.5 based upon empirical data and risk assessment done by professional statisticians, cardiologists and medical device engineers.

Hey Tom, I'm a BAV St Jude guy in the aortic position just like you

I understand your colon point but with regard to the range you cite i am failing to find papers
on this, would you be so kind as to link any, i like to dial into the detail.

my hospital papers show my range 2.5 to 3.5 ( target 3 )

I can find papers on the St Jude at 2 to 3 ( target 2.5 ) in the Aortic position

I have no other factors and aim 2.5 to 3.5 I also do not use ASA

any links would be appreciated , Thanks


EDIT , slight edit to clear up the wording ......

 

[BillDaThrill]

So is St Jude (now Abbott) also pushing for a lower INR for its valve now? Seeing Leadville's post above made me use 'the Google' - and found this page on Abbott's website: Aortic Valve Regent™ Clinical Data | Abbott
The page proudly shows 4 studies whereas SJM valve patients used lower INRs (1.5 - 2.5). Man, that sure sounds like they are also pushing for lower coagulation - perhaps trying to match the claims of the On-X valve. Interesting times...