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

[pellicle]

You mean 26 events per 100 patient years, right?

yes

Also "The dutch study" is made on a much older population.

not significantly so ... btw, do you know what it is I'm talking about (I didn't cite it)

 

[henkac]

Can you please link your source? Perhaps you are citing a different study

LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial - PubMed

LOWERING-IT trial established that the proposed LOW-INR target is safe and feasible in low-risk patients after bileaflet aortic mechanical valve replacement. It results in similar thrombotic events and in a significant reduction of bleeding occurrence when compared to the conventional...

pubmed.ncbi.nlm.nih.gov

It's the Lowering IT study you linked to in your earlier post regarding the 1:3 ratio.

 

[henkac]

yes



not significantly so ... btw, do you know what it is I'm talking about (I didn't cite it)

The tabel you posted above is this, right?

Being used in thus study from the Netherlands:

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

Background Oral anticoagulant therapy is effective for the prevention of arterial thromboembolism in various patient groups. The increased risk of hemorrhage remains the major drawback to this therapy and is associated with the intensity of anticoagulation. Finding the optimal intensity at...

jamanetwork.com

So I assumed it to be "the dutch stud". Hope I'm not totalt out of bounds here

 

[henkac]

not significantly so

I wouldn't discharge the age difference in age as of low significance.
Lowering IT mean age 49, Proact 55.

The dutch is not giving us a clear mean age but viewing how they diveded age groups it's clear it's a significant older population. Specially since most research would say risk of events hit a big bump around the age of 65. Haven't found many studies at all with an mean age well below, as both Lowering an Proact. That if anything should be an argument to use against the Proact compared to other studies, if anyone wants to argue against it. Not employees getting nice dinners to lie or false calculations.

 

[pellicle]

Hope I'm not totalt out of bounds here

nope ... just wasn't sure if you knew the indirect "idiomatic" reference ;-)

I wouldn't discharge the age difference in age as of low significance.
Lowering IT mean age 49, Proact 55.

Well personally I would have suggested that those age groups were essentially equivalent in terms of physiology, what is it that you have which suggests otherwise?

Also the "Dutch Study" has a much much greater significance in terms of statistics both in the number of people involved and the durations (wouldn't you agree?)

 

[henkac]

Also the "Dutch Study" has a much much greater significance in terms of statistics both in the number of people involved and the durations (wouldn't you agree?)

Dutch: 483 patiens for 1.149 p-years (Mec Valve)
Lowering IT: 396 patients for 2.217 p-years
Proact: 375 patients for 1.426 p-years

 

[pellicle]

Dutch: 483 patiens for 1.149 p-years (Mec Valve)
Lowering IT: 396 patients for 2.217 p-years
Proact: 375 patients for 1.426 p-years

but the study I am quoting is this:

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

Background Oral anticoagulant therapy is effective for the prevention of arterial thromboembolism in various patient groups. The increased risk of hemorrhage remains the major drawback to this therapy and is associated with the intensity of anticoagulation. Finding the optimal intensity at...

jamanetwork.com

Methods We evaluated all patients visiting the Leiden Anticoagulation Clinic with mechanical heart valve prostheses, atrial fibrillation, or myocardial infarction from 1994 to 1998. Untoward events were major thromboembolism and major hemorrhage. We calculated intensity-specific incidence rates of untoward events to assess the optimal intensity per indication of treatment. We enrolled 4202 patients for a total of 7788 patient-years.​

or are you subdividing out patients with specific criteria?

 

[henkac]

Lowering IT and Proact is strictly looking at Mechanical valves. The dutch also includes Atrial Fibrillation and Myocardial Infarction (majority of patients). It wouldn´t be fair or give us any valuable information to compare LowIT and Proact to something different then they try to answer. Apples to apples and pears to pears.
The numbers I´m referring to are for Mechanical Vales in the Dutch study you refer to.

 

[Chuck C]

LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial - PubMed

LOWERING-IT trial established that the proposed LOW-INR target is safe and feasible in low-risk patients after bileaflet aortic mechanical valve replacement. It results in similar thrombotic events and in a significant reduction of bleeding occurrence when compared to the conventional...

pubmed.ncbi.nlm.nih.gov

It's the Lowering IT study you linked to in your earlier post regarding the 1:3 ratio.

Ok, thanks.
To be clear, that study was not the study used to establish the lower INR for On-X as being "not inferior". Lowering IT did not even include the On-X and the lower INR group had a range of 1.5-2.5.

I do hope that the proposed study goes forward, as is supposed to evaluate the 1.5-2.5 INR for mechanical valves, and would appear that it is not focusing on any one valve. It could therefor end up being somewhat of a direct comparison for On-x vs St. Jude, especially at the lower target range.

I'm personally more comfortable with the range of 1.5-2.5, as this would make the target number 2.0, and if managed properly, would result in an average of about 2.0. I think that is somewhat safer than targeting 1.5-2.0. Personally, I'm going to have to see a lot more data to convince me that I should target anything lower than the 2.0-3.0, which is another way of saying targeting 2.5. A study with 400 participants will not likely convince me. That would be about 200 in each arm and not create powerful data in my view.

 

[Protimenow]

The accepted 'error' in INR measurement is 20% +/- the actual INR. If your 'acceptable' range is 1.5-2.0, then a meter reading of 1.5 could, possibly, be as low as 1.2. Even at 2.0, it could conceivably be 1.6, and be considered within acceptable accuracy.

Even if I had an On-X valve, I would certainly NOT be comfortable with an INR that my meter reports to be 1.5. FWI - even if I had an On-X, my target would be 2.5 if not higher.

A lower INR - even if On-X says it's okay - is of no actual benefit - and can increase the risk of stroke. Maintaining an INR of 2.5 - 3.5 (a target of 3.0) doesn't really have any effect on life style, or interfere with most activities (I may advise against rock climbing, kick boxing, and things like that - the bruising may be a bit greater).

Personally, I see an INR below 2.0 - even with an On-X - as being of no real value. The risk vs. benefits calculation just makes the risk too high compared to any possible benefits.

I've anticoagulated since 1991. Except for the times that INRs were supposedly above 5 (maybe not, could have been lab error), I don't recall any significant issues with high INR (but I was a bit more careful if it actually WAS that high), but had a serious issue when it was low and my meter 'lied' to me.

 

[carolinemc]

One reason might be that the On-X valve is being used almost exclusively a lot of the major heart surgery centers. Examples: My hospital (Washington D.C. Hospital, MedStar) will install an On-X. I don't even know if they install other mechanical valves . Not mentioned or discussed. And I didn't know any better to ask. The On-X was recommended by my surgeon (for the good or the bad ). There are other major centers that are the same like the Franciscan Health Heart Valve Center.

I am very curious as to the number of On-X aortic valves installed in the past 2 years as compared to the St. Jude's here in the states. Not sure if that data is even available .

FWIW, ball smashers are only being used by angry spouses at this point right? (relax everyone, just a joke!).

On-x is not the only valve out there. I have a St. Judes' leaflet valve and it has been since 2001, so it has been 22 years in September. Most hospitals offer what the hospital will allow. But with the St. Jude and On-x valves you do still have to take a blood thinner, but you test more on the St. Jude to adjust the medication.

 

[nobog]

On-x is not the only valve out there. I have a St. Judes' leaflet valve and it has been since 2001, so it has been 22 years in September. Most hospitals offer what the hospital will allow. But with the St. Jude and On-x valves you do still have to take a blood thinner, but you test more on the St. Jude to adjust the medication.

Sorry, that makes no sense whatsoever.

 

[pellicle]

Lowering IT and Proact is strictly looking at Mechanical valves. The dutch also includes Atrial Fibrillation and Myocardial Infarction (majority of patients). It wouldn´t be fair or give us any valuable information to compare LowIT and Proact to something different then they try to answer. Apples to apples and pears to pears.

I see ... as I suspected you're pulling out the data which you feel doesn't match your selection criteria. However I don't think that's fully valid unless you are looking only at the stroke levels (which we are) but there is still value to be had from the other groups in that (I can discuss if you like). For instance can you be sure that no amount of afib will be present in your patient? What amount of platelet aggregation is being triggered by other factors than "mechanical valve". It becomes vexed and in my view requires a more deft and skilled hand at determining discounting than I feel I have. If on the other hand you feel you have more experience than me and better training in the analysis of study data then as long as your confidence is high in that its fine..

However it is considered proper to explain what you are doing and why when doing that sort of thing.

Best Wishes

 

[henkac]

as I suspected you're pulling out the data which you feel doesn't match your selection criteria.

Reading and analyzing research data on a daily basis has been a part of my job for the last 15 years so I feel pretty at home. (Not about heart valves and warfarin though.) The more you learn, the more humble you get too however, due to understanding how often you make mistakes and how little you actually know from the whole picture.

If I have more or less experience than you, I have know idea of. And it doesn´t matter that much I think. I´ve grown in insight from people who just started reading science and I´ve met some real seniors being the most biased people I´ve met. I think in what spirit you seek knowledge is most important. Of course experience in how understanding study design and reading numbers will help at the end of the day.

I´ve actually never been told to be cherry-picking for claiming we should only use apples to compare with other apples (compare the same things between studies). And it wasn´t really my point when I joined this thread, pointing out there was some data being referred to incorrectly by mistake.
But maybe you´re right about the cherry-picking? I have to think about it. Not a bad outcome from a discussion either. Self-reflection.

 

[pellicle]

But maybe you´re right about the cherry-picking? I have to think about it. Not a bad outcome from a discussion either. Self-reflection.

well I wasn't directly calling it cherry picking but would wonder about discounting things which may be related.

Either way, as long as you look at the big picture too and see that across a whole bunch of sets the INR data emerges more robustly than across one smaller set.

Also, neither set closely represents your target application (yet, and you may not live to see her in the 60yo group). Myself I think that the answer is pretty clear: steer the INR to between two and three unless evidence emerges for your case to steer it higher. There could be cases of activity where steering it lower in a short term could prove prudent. Personal data would need to be gathered and cost benefit risk analysis undertaken (in a mostly conjectural environment).

Personally I would not call any significant difference between 55 and 60 age groups, as too many other factors will account for differences.

I personally think you're over analysing (and may be here) but then that's just my opinion (based on a restricted view).

Happy to help in the iterative reflection process, I hope I've been a good sounding board.

Best Wishes

 

[henkac]

I personally think you're over analysing (and may be here)

Yes, that's probably it.
Thanks for helping me out with reflecting.

 

[nobog]

Sorry, that makes no sense whatsoever.

Angry? If you could give the scientific reason why you need to "test more" with a SJM valve I'm all ears.

 

[tom in MO]

I am not sure that this is an accurate statement. Once these devices are out in the real world the reporting on problems becomes much less stringent. Having a stroke with a mechanical valve is a known complication and would not necessarily trigger a report to the FDA.

Usually the device manufacturers will negotiate pricing with the hospital or hospital system for the best deals on the devices. If the surgeons don't complain too much these have now become often corporate decisions. As far as the corporate world is concerned if the device is FDA approved it is OK. What levels of anticoagulation have nothing to do with these corporate decisions.

Basically if you are more worried about bleeding go low on your INR. If you are more worried about strokes go higher. Personally I am more worried about strokes so an INR of 2 or less makes me nervous.
In all the studies I have seen with low INRs the stroke rates are higher with the low INR patients. This absurd statistic of combined stroke+bleeding which usually looks favorable for the low INR group is a dumb statistic. The effects of strokes and bleeding usually are quite different.

Ultimately I don't think the people working for these companies are inherently evil but they have their biases and the bottom line is they have to sell these devices to survive.

Doctors are also inundated by these "detail" people who push their products. Doctors are not all knowing and don't have the time to research ever little detail. So they can be influenced by these detail people.

I as a physician have always been leery of what I hear from them when they come to my office. But they clearly have influence or the drug/device companies would not continue to employ them.

When I asked about the On-X before my surgery, I was told that the hospital didn't stock it but if I wanted it my surgeon would get it in. I asked why they didn't stock it, and the surgeon said they only have so much room and his valve of preference was the St. Jude. They have to have valves on hand for emergencies, but any valve can be ordered. I asked why St. Jude was the one in stock and he said it had a long history of good performance and he preferred historical data rather than something new with less data on long term use.

 

[pellicle]

Angry?

ahhh the angry face ... I think myself its entirely stochastic.

So she's just doing what comes natural to her, doing a Caroline or is that simply just a Caroliner


remember, there is no entrance exam to qualify for having Valvular Heart Disease

 

[Humboldtgrrl]

My practice is involved with a large number of drug studies on eye drugs for various retinal conditions. When these studies are initiated a lot of thought goes into trying to design the study as likely to work as possible. Recently one of the drug companies had a failed study. They analyzed the study and decided that the way it was set up allowed the study to fail. So feeling confident that their product would ultimately pass muster they set up another study done slightly differently which they hope will succeed. This INR stuff is a lot like that. Concoct weird statistics (adding bleeding+stroke) showing they are "superior" in one group and getting the FDA to OK this device. Also I think there is a trend for the FDA to OK things that possibly in the past would not be OKed. For example one of the drugs for Alzheimers was authorized even though it did not show direct clinical efficacy for Alzheimers. It only showed a marker being altered. Somewhat like the defense industry in the US there is a revolving door between government and industry in other departments like the FDA. So there may be conflicts of interest in making these decisions.