Failure of Onx valve and problems with lowering INR

[pellicle]

...I have seen the On-X advertised a lot since I started looking around AVR forums, (I have a St Jude) and am surprised nobody else who has one has commented so far.

myself I've long been interested in the "long term viability" of their protocol. I have some reservations about the long term issues of thrombosis if one was to "skate on the thin ice" of INR=1.7 as a target with such things as valve thrombosis obstructions. Cheries experience suggests perhaps the protocol requires further study.

Myself I've also noted that the design and haemodynamic testing against the St Jude shows it to be quite similar ... and the various recent studies have shown that INR = >2 to be the safer minimum with respect to the St Jude, so I have always wondered about that.

Lastly I noted here that some On-X patients have had their medical team act more conservatively (higher INR targets) and have complained about it ... perhaps this experience may alter their views?

dunno

 

[ClickityClack]

This has been an interesting thread to read, though I am very sorry, Cherie, for all that you have been through, despite your protestations to medical professionals. I have seen the On-X advertised a lot since I started looking around AVR forums, (I have a St Jude) and am surprised nobody else who has one has commented so far. There must be somebody else who has one here? Any experiences to add?

I have an On-X but no problems yet. It's still early days for me though. They just lowered my range to 1.5 - 2.0 a bit over two weeks ago. I am taking the aspirin as well and have been since surgery. I'm at 1.7 as of Tuesday night.

I feel the 1.5 - 2.0 range is definitely too small. I've been testing weekly and took it upon myself to add a mg every other day this past week. Considering Tuesday's result, I'm fairly certain that the clinic's 'hold' instruction would have me at or below 1.5.

Is 1.5 too low? I don't know. Likewise, I have very low confidence that it is safe. I tried to get my primary to bump the range up but he chose to kick the can to my cardiologist whom I see in two weeks. In the next breath he said that's he's not seen a range so low and that 1.7 would not normally be considered therapeutic.

Cherie's chilling experience reinforces one of the things that I suspected since first seeing the PROACT and similar trials - that aspirin is a critical portion of this low INR anti-coagulation protocol. Then again, the incidence of thromboembolic events has never been zero in any study I can recall. Technically some level of risk is always there for all of us with mechanical valves.

How much effect does aspirin generally have on INR? I know it works differently than warfarin so there may be a benefit that cannot be quantified with INR but I have yet to see any such benefit defined.

*snip*
Obviously aspirin was part of the anticoagulation therapy. Yet I do not react to aspirin as needed. yet the conclusion states "combined with aspirin", which I don't react with. Yet inclusion criteria references you can include those with lack of platelet response. So why does conclusion specifically state "combined with aspirin". Hope I am making sense.

The inclusion criteria for the PROACT actually states that patients are in the low risk group (the Plavix group, I assume) unless they have any of a list of conditions that included "Lack of platelet response to aspirin or clopidogrel." The very interesting thing is that you were removed from the study entirely rather than being moved to the high risk group. Were you actually removed from the study or were you put in the high risk control group?

 

[Cherie']

pellicle I agree that the obvious is the mismanagement by the medical team. It was a violation of medical standards of care to change something that had been working for over five years. Trust me I've learned a lot on this journey. Basically, often times you cannot rely on your medical team. You have to do your homework and advocate for yourself. I am paying the price. My life has been forever impacted and not in a good way.

ClickityClack as someone who has lived this journey I would definitely NOT maintain your INR below 2.0. I'm not the only one that has had this experience. I know for a fact there was another patient when I was in the hospital that had and on X valve, lowered the INR, and was struggling for their life. My advice to you is to maintain your INR between 2.0 to 3.0 as originally specified by on X before the approval of the FDA study. Let's put it this way I was fine for five years. Within weeks of the letter from On-x and the lowering of my INR by my cardiologist, I started having difficulty walking. I would later learn, after my second open heart surgery, that pains in your legs is one of the first signs of improper anticoagulation.

I was removed from the study entirely! That is an excellent point! If I was a candidate at all for the study On-x would have moved to me from the low risk group to the high risk group. Which that in itself begs the question … How can someone not be appropriate for the low risk group be appropriate for the high risk group? AND it also begs the question why would they send me the letter for the high risk group knowing I was already removed from the study? so much to think about.

Not sure if this was your first open heart surgery or not, but I highly recommend that you maintain an INR of 2.0 to 3.0. Whatever any practitioner tells you maintain your range at a bare minimum of two. And I highly recommend above that. The second time is a lot less fun. Recovery has been much more challenging. My first surgery was 13 hours my second was eight hours. Please heed my advice. You are the one that will be on the operating table, not your treatment team. Just saying...

 

[pellicle]

Hi there

I agree that the obvious is the mismanagement by the medical team. It was a violation of medical standards of care to change something that had been working for over five years.

totally ... I mentioned what I did above from the perspective that pursuing a medical team will have totally different resistance levels to pursuing a large medical company who simply would not want a precedent set. You must be prepared for a long and dirty fight if you to the medical company. The other guys have insurance...

Trust me I've learned a lot on this journey. Basically, often times you cannot rely on your medical team. You have to do your homework and advocate for yourself. I am paying the price. My life has been forever impacted and not in a good way.

Understood. I often advocate here for the principles of patient education (and not just fluff, but learing what you don't know and learing how to learn that so that you do know it. Its often difficult because few people have the capacity to undertake critical analysis and really get to know terms. Too many stop at "face value" even if they do actually read studies.

Self advocation is also one really important thing. I believe that it goes hand in glove with the education, for you have to understand something to argue the case (as well as be prepared to actually take responsibility for outcomes).

On a philosophical note, time is a tide that is always going out, we can't save time (as we can money) and the passage of time changes us. We never are who we began as. Its up to each of us to accept that truth and attempt to steer ourselves (irrespective of the storms which may dash us on the rocks) into "better people" ... In my own recoveries I have always said (mainly to myself) that I want to get better, not bitter.

Best Wishes

 

[Mister_James]

First, people have thrombosis with an INR of 1.0 and 1.0 to 1.5 is considered Normal.

Second, a mechanical valve is a foreign object and its blood dynamics will never be insignificant compared to bio-prosthetic or natural valves.

Third, any other complication such as afib will make you susceptible to thrombosis.

While a 1.5 -2.0 INR sounds sexy, a 3.0 will not be the end of your life and in my opinion, that is the sweet spot to aim and Note there is still incidences of thrombosis even at that level but they are at the low to bleeding risk adjusted

 

[ClickityClack]

Well it looks like my cardiologist is going to be stubborn about sticking with the 1.5 - 2.0 INR range recommended by the surgeon. His office called and said that he had confirmed it with the surgeon.

I meet with the cardiologist Thursday but I haven't found much published information regarding lower INR ranges and the aortic ON-X valve. I've found the interim PROACT results and this: http://onlinelibrary.wiley.com/doi/10.1111/j.0886-0440.2004.04084.x/full

Does anyone know of anything else that would be relevant, on either side of the issue?

 

[pellicle]

Hi

Well it looks like my cardiologist is going to be stubborn about sticking with the 1.5 - 2.0 INR range recommended by the surgeon. His office called and said that he had confirmed it with the surgeon.....

I meet with the cardiologist Thursday but I haven't found much published information regarding lower INR ranges...

Does anyone know of anything else that would be relevant, on either side of the issue?

Ok, here's a few hours of my time ... the situation is that there just isn't an off the shelf answer to this question and so one has to cease being an automaton and apply ones own cognition to the findings that have been published.

Ultimately the answer to this question is found in this statement:

"It should be the goal of the clinician to balance the patients desires for how they are managed with reducing risk to the patient"

So, lets discuss risks (and you can discuss patient desires).

This is the argument I'd make to your cardiologist.

1) there is a lack of evidence to support the idea that long term the On-X protocol is safe for everyone. Fundamentally all studies are about statistical application. If you are "the norm" then "you" fit into their findings. To argue otherwise shows a total lack of comprehension of how statistics works.

2) The studies on INR management targeting the lower than 2.0 have been quite specific with inclusion and exclusion criteria. Has exhaustive testing (or indeed any testing) been done on you to determine if you are inside that criteria? The On-X protocol is not a "law" it is a guideline towards what they believe the lower the safe lower end of the INR range could be for the people in their study who met the inclusion criteria.

3) The evidence we have today shows that INR between 2 and 4 is the safest area I refer you to the study published in this Journal: http://jamanetwork.com/journals/jama...article/415179

It is a study 4202 patients, quite comprehensive. From that article: [IMG2=JSON]{"data-align":"none","data-size":"full","src":"https:\/\/c2.staticflickr.com\/4\/3868\/14626794599_c646b1872d_b.jpg"}[/IMG2]




so we can see that INR target = 2.5 is not only safe, but gives you ample room for the variations of daily life.

3) while there is short term study on the lack of thrombosis on the patient (such as the PROACT trial and the ESCAT III trial) there is no long term study on the possibility of valve obstrction thrombosis or indeed on the possibility of panus formation (which has been linked to INR being low).

4) The measurement of INR is inherrently fraugh, and while simply expressed as the ratio of (Patient clotting time) OVER (normal clotting time) what is omitted is much. For instance "normal clotting time" varies among the population, what was YOUR un-anticoagulated ProThrombin time? For example were your PT time longer than "average" it would mean that a measured INR of 1.8 would put you much closer to your un-anticoagulated levels ... which is potentially harmful.

I recommend you consider this article as a primer on that topic:
http://www.coaguchek.com/content/int..._time_INR.html

In short there is no evidence that you will increase your risk of harm with increasing your INR target to 2.5 and indeed some evidence that you will increase your risk of harm if you were to persue an INR of less than 2.0 for any length of time.

I'd put that to them

also worth reading is this (a ref to a pdf from my evernote, you can chase the original yourself
https://www.evernote.com/shard/s223/...9880-5-319.pdf

 

[ClickityClack]

pellicle I really, really appreciate the time you've taken with this.

I can't help but wonder if I am to be included in this next study seeking to support the long-term safety of low intensity AC for patients with ON-X valves. I knew the valve was newer than most but it never occurred to me that I'd be one of the retrospective guinea pigs.


In any case, I appreciate your perspective on the Dutch study. I had dismissed it because the data was collected prior to the widespread use of ON-X but it does serve as a strong baseline for 'traditional' AC ranges.


I believe this is the original article that your evernote link referenced: https://www.omicsonline.org/open-ac...tensity-regimen-2155-9880-5-319.php?aid=27204

It is a good synopsis of the evidence even though it is clearly biased toward the adoption of lower INR regimens.


I have to admit that reading these studies has me optimistic about low INR regimens. Clearly though, the results have to be utilized with caution. Cherie' was outside the criteria from the start and interim PROACT results were applied to her without regard for the limitations of said results. The limited size of the supporting trials, along with their strict inclusion criteria are excellent points that don't get nearly enough attention. INR measurement is another good argument, though I had that one in the bag as a result of our previous discussion

I'll let you know what comes of our discussion. Thank you again!

 

[drivetopless]

Hi, Cherie- Glad you are doing better. That was really scarey to read about, but thanks for sharing. I got my On-X at the same time as you-- January 2011. I've been maintaining my INR between 1.5 and 2.5 the last few years with warafarin + baby aspirin. No clot issues so far - knock on wood. But I have experienced like many here that we have to be our own advocates and educator many times. Everyone's body chemistry is different and these surprises can pop up. Keep us posted on your progress.

 

[ClickityClack]

So he said he'd write the order to bump my upper bound to 2.5 if the nurses running the AC clinic were okay with it. Nobody wants to go against this surgeon. I guess it's one of the drawbacks of getting the best valve guy in the area.

He offered me a job after I started talking about the faults of the studies though, lol.

 

[pellicle]

Hi

firstly, I'm glad I could help (and thanks for the thanks)

So he said he'd write the order to bump my upper bound to 2.5 if the nurses running the AC clinic were okay with it. Nobody wants to go against this surgeon. I guess it's one of the drawbacks of getting the best valve guy in the area.

sounds like a good outcome to me

... and yes that was the article. I found it interesting reading, valuable. For interest most of my time in preparing that short post was in going through my notes and making sure that my interpretations were sound, as well as determining how to be succinct (meaning what to omit).

My personal take on the research is that the new bileaflet mechanicals in concert with the greater understanding of and tools available on how to manage INR (not a trivial development in itself) has opened up greater advances in this highly specialised application of warfarin therapy (remembering us valvers are a tiny percentage of overall AC Therapy)

I see the grasping of the suitability of lower levels of AC therapy to be a way to move the bounds down thus allowing more "fudge factor" and less concern of INR "squiggle". The results of the On-X sponsored studies (among others) make it clear that dipping down to 1.5 (or hovering around 1.9) is not harmful.

What we don't know yet (there have been no studies) is if such lower INR levels increase risks of obstructive thrombosis (now treatable with tPA rather than surgery in some cases) or other related adhesive thrombosis issues.

We are learning the bounds.

What I see as the next step is to incorporate personalised understandings of ones INR responce and incorporating that into a model which allows you to:

1. feel comfortable with the safety of the dose you're on
2. know when to make a change in dose as required

Much is made of the wording in many papers mentioning INR, more than is warranted. For instance much is made of the point that dose needs to be "frequently adjusted" ... perhaps this is "frequent" for the typical doctor who would thinks in terms of hypertension medications which may need yearly review. For a drug which is tied more tightly to metabolism the sort of adjustments I do (hardly even monthly and then minor) it hardly bears mentioning ... ask a diabetic about their regime...

He offered me a job after I started talking about the faults of the studies though, lol.

LOL ... go man go!

 

[pellicle]

pellicle

I can't help but wonder if I am to be included in this next study seeking to support the long-term safety of low intensity AC for patients with ON-X valves. I knew the valve was newer than most but it never occurred to me that I'd be one of the retrospective guinea pigs.

they're always after "live ones"

;-)

I believe this is the original article that your evernote link referenced: https://www.omicsonline.org/open-acc....php?aid=27204

indeed it was ... one of the opening paragraphs remains one of my recent favs

However, significant improvements, the quest for the ideal valvular prosthesis is still ongoing. Indeed, current tissue valves are still prone to structural deterioration, while modern mechanical valves display an inherent thrombogenic potential. Despite in nearly every study performed, mechanical valves seem to improve survival, definitive quantitative data are still lacking.

I have some suspicions on the reasons for lack of evidence and quality study. Key points are:

• good research costs, where is the financial benefit to valve makers?
• most people are slack, disorganised and unreliable, so therefore recommending a pathway on which their optimal outcome depends on them being organised and dilligent is fraught ... better to let them have option B
• once a surgeon has given a 60 year old an extra 10 to 15 years (by doing a valve surgery VS them dying of stenosis) what would it matter to them that you got 20 years or 30 years more?
• if you need to have more expensive treatments as you age (such as transcatheters or other valve replacement methods as your tissue prosthetic wears out), then that's good for the medical industry (perhaps not you nor society)
• proper Oral Anticoagulation therapy is cheap, no money to be made there. Its no surprise that countries where universal health care is provided FREE to citizens are more interested in it than countries where the medical system is a money making business.

Just my view

 

[Nocturne]

One thing docs seem to be great at is waving their hands and exclaiming, "FUHGEDDABOUDIT -- ya gonna be FINE!!!" -- when you most assuredly are NOT. I think they take coursework in it. I'm sorry you had to go through this. Wish I had more to offer.

 

[DJM 18]

For those who have not seen it the Italian study referenced below is of some value in the context of this discussion. But what I found interesting is that what they seem to stress is more patient specific, that is understanding that there are lower risk patients and higher risk patients. While the On-X claims that their valve may lower your risk profile (just like a bileaflet would over a tilting disk or a caged ball), it does not make you a lower risk patient. In this study of almost 200 patients (and an equal number of controls) which covers more than 1,000 patient years they achieved very good results with an INR taget of 1.5 to 2.0 but only when applied to low risk patients. Interestingly, most of the patients had the Sorin Bicarbon and the remainder a St. Jude medical bileaflet. And I do tend to agree that it does not seem to make too much sense to aim so low, as with most things in life best to always have a good margin for error...and as pellicle likes to stress, what perhaps matters most is compliance with the stated regimen. Also important as they emphasize in the study, a patients risk profile may change over time / circumstances. "Thus, it has to be emphasized that the data of the LOWERING-IT trial are related only to a low-risk patient population undergoing single AVR. Hence, it has to be underlined that in perspective, the long-term mainte- nance at the suggested low INR range would clearly require adjustment in these “low-risk”patients whose risk characteristics change over time" Valvular and Congenital Heart Disease LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: Results from the “LOWERING-IT”Trial Background Moderate anticoagulation after mechanical heart valve replacement has been proposed to reduce the risk of bleeding related to lifelong anticoagulation. However, the efficacy of such reduced antithrombotic regimens is still unknown. The present prospective open-label, single-center, randomized controlled trial aimed to evaluate the safety and feasibility of reduced oral anticoagulation after isolated mechanical aortic valve replacement. Methods Low-risk patients undergoing bileaflet mechanical aortic valve replacement were randomized to a low International normalized ratio (INR) target (1.5-2.5; LOW-INR group) or to the standard currently recommended INR (2.0-3.0; CONVENTIONAL-INR group) through daily coumarine oral therapy. No aspirin was added. Median follow-up was 5.6 years. The primary outcome was assessment of noninferiority of the low over the standard anticoagulation regimen on thromboembolic events. Secondary end point was the superiority of the reduced INR target strategy on bleeding events. Results We analyzed 396 patients (197 in the LOW-INR group and 199 in the CONVENTIONAL-INR group). The mean of INR was 1.94 ± 0.21 and 2.61 ± 0.25 in the LOW-INR and CONVENTIONAL-INR groups, respectively (Pb.001). One versus three thromboembolic events occurred in the LOW-INR and CONVENTIONAL-INR, respectively, meeting the noninferiority criterion (P= .62). Total hemorrhagic events occurred in 6 patients in the LOW-INR group and in 16 patients in the CONVENTIONAL-INR group (P= .04). Conclusions 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 anticoagulation regimen. (Am Heart J 2010;160:171-8. Available from: https://www.researchgate.net/public...eplacement_Results_from_the_LOWERING-IT_Trial [accessed Sep 27, 2017].

 

[dcc617]

As I'm sitting here sucking on my 1st cup of coffee, this chat string caught my eye. I'm scheduled for aortic valve replacement on 10/30 (the latest I was allowed to schedule it). My porcine valve place 5.5 years ago is failing. Actually, one of the leaflets has torn. I'm mulling choices of another organic valve or mechanical. The surgeon talked about the ON-X as an option since warfarin doses are lower. I have until the anesthesia hits to choose. I was thinking of going mechanical but now this string is making me think. Thanks for posting this. I just need to fully awake to read everything.

 

[dick0236]

After 50+ years on warfarin I have never understood all the flap about lowering the warfarin range to under 2. My range has been 2.5-3.5 since the inception of INR testing, +/- 30 years ago and I have had no problems with that range.......no bleeds, no strokes, not even excessive bruising.

 

[pellicle]

I would second dick0236 above. The accumulated data across thousands of patients kver dozens of years shows consistently that unr between 2 and 4 essentially poses no more risk than the age related risk of the general population for all issues. The perception if warfarin being harmful is a direct consequence of its mismanagement by the so called usual care. The whole issue of lowering the warfarin dose is predicated in a fear of warfarin as if it was somehow like exposure to radiation.

 

[pellicle]

dcc617 Somethings to ponder while sipping your coffee and considering that properly informed patient decision http://cjeastwd.blogspot.com/2014/01/heart-valve-information-for-choices.html Still, this will only be your second operation, no need to get too worried about redo surgery posing significant risks till your third

 

[Silver Bullet]

My recollection is that there were 2 OnX clinical trials. One was warfarin vs no warfarin. The no warfarin group received ASA and Plavix and this is the one that required subjects to be ASA sensitive. This study has never been reported to my knowledge. The second study was INR2-3 (plus ASA) vs INR 1.5-2 (plus ASA). We all know about this study and it did NOT require ASA sensitivity. It is the basis for the INR1.5-2 recommendation for OnX valves but note that this recommendation requires concomitant low dose ASA.

 

[Protimenow]

I'm very late to this thread, and than Pellicle for putting the link into another thread.

As others have said, there's really no change in life style, or other things with having an INR between 2 and 3 - or even as high as 4, versus an INR of 1.5 - 2. Previously, according to some papers that I've read, for St. Jude Aortic valves, recommendations of INR as high as 4.0 were common. Today's recommendation of a target of 2.5, with a range of 2.0 - 3.0 should be easy to accomplish and manage. This 'safe' level should also be applied to the On-X.

The drug reps (called 'detail' persons in the United States) have done a great job of convincing many cardiologists, cardiac surgeons, and the people who run the clinics that a range of 1.5 - 2.0 is recommended for anyone with an On-X valve. This is probably the reason that some practitioners vehemently oppose patients using a safer range.

Also, as noted previously, INR testing isn't exact -- results can very from lab to lab and from meter to meter. A lab or meter result of 1.5 would scare me - the 'actual' INR (if such a thing exists) may be closer to 1.2 or 1.3. Aiming for that low value just isn't worth the risk.

Again, as I've said in other forums, and others have said here -- having an INR between 2 and 3 doesn't affect your life any more than having an INR between 1.5 and 2.0 (with the exception that the higher INR would help reduce risk of a stroke or pulmonary embolism). Aside from marketing reasons, I see no logical reason to maintain an INR between 1.5 and 2.0 - even with an On-X valve. Until they come out with a valve that has no risk of clots forming on it - with no medication required to assure that safe outcome, maintaining an INR that's a minimum of 2.0 will still be the safest level of INR management.