On-X and Lower INR Protocol

[MrsBray]

I got my OnX 3/2014 at age 42. Target range post-op was 2.5-3.5. After receiving the letter from OnX and delivering it to my cardio, my primary, and my nurse, I am approved for 1.5-2.0. My nurse and I (hey, i see her every 5 weeks, I trust her) keep my INR around 2.0-2.3. I was having a lot of bruising with above 3.0. I'm looking forward to following Europe's lead and doing low-dose aspirin only. But I'm not in a rush.

-Meredith

 

[pellicle]

Hi

pardon me, but do you have any refs to this? I've not heard of this...

.... I'm looking forward to following Europe's lead and doing low-dose aspirin only.

 

[Ryan CA]

Hi

pardon me, but do you have any refs to this? I've not heard of this...

Hey Pellicle....I read the same thing about the aspirin only study in europe; although I cant remember where at the moment. Figures, haha.

 

[pellicle]

Hey Pellicle....I read the same thing about the aspirin only study in europe; although I cant remember where at the moment. Figures, haha.

damn, this is tantalizing ... I am turning up nanda on google (enuff to make me question my google skills)

hay, and was meaning to say earlier:

• glad you're back in the saddle (I recall some of the earlier conversations)
• thanks for the feedback about sticks and stone scratches as I've found something similar when using the "line trimmer" ... being a Queenslander I often just wear shorts and it flicks stuff allover my legs. With INR > 2.5 I get a few ding and dribbles, but with lower INR I don't.

I found one article about an african american fella that did something like 23 years on a StJudes with NO AC therapy.
http://icvts.oxfordjournals.org/content/8/2/263.full

nothing about the study though.

PS, in case line trimmer is "austraylian vernacular"

 

[Silver Bullet]

Eric, at the age of 39, I certainly agree that a mechanical valve makes the most sense. A Ross procedure also makes sense if you can get a surgeon who is a master at doing it, preferably with published results indicating excellent long term outcome (like Dr. Tirone David) and if your aortic root is not dilated. In similar shoes to yours, I didn't like the idea of creating a situation where I had to worry about 2 valves, so I chose to go with a mechanical valve.

As a Cardiologist, my sense is that the top Cardiologists and Cardiac Surgeons are skeptical that only the On-X valve can safely be used with INR1.5-2 plus ASA. The problem is that there isn't any evidence that such a regimen is safe with other valves. This is a case where absence of evidence does not equal evidence of absence. It could well be that all modern bileaflet valves in the aortic position of low risk patients can safely be managed with INRs of 1.5-2.0. We just don't know. The downside of the On-X valve is that it hasn't been around as long as the others and though it's longevity so far seems good, we also just don't know what the future will hold. Also, keep in mind that only one relatively small clinical trial that was sponsored by On-X exists suggesting that an INR of 1.5-2 is safe. Good science demands that provocative findings be repeated. Of course, that almost certainly won't happen for practical reasons, but it's nevertheless reasonable to conclude that the evidence favouring a low intensity INR range for the On-X valve is not based upon the best possible evidence, so there remains some room for skepticism. While the evidence satisfied the FDA (doesn't actually take much to do that), it hasn't seemed to change the minds of those cardiac surgeons who write guidelines and speak at valve conferences.

As for your job, I think that you need to make the choice that's best for your health first, and worry about your job later. If I were you - a firefighter - my worry would be suffering head trauma while anti coagulated. That could be devastating. How often does your job result in a bonk on your noggin?

A good thing to remember is that bleeding complications on warfarin in young people are rare. Bleeding on warfarin is mostly a problem for older people. Also remember that structural bioprosthetic valve deterioration occurs earliest in young people. Accordingly, the younger you are, the more, I think, a mechanical valve makes sense.

 

[pellicle]

Hi

... The problem is that there isn't any evidence that such a regimen is safe with other valves. This is a case where absence of evidence does not equal evidence of absence.

maybe not much evidence of the INR < 2, but there is the GELIA study:

http://www.ncbi.nlm.nih.gov/pubmed/8269143

In a study population of 2,735 patients, GELIA compared three different intensities of oral anticoagulation in a prospective and randomized design.

some notes I made from it

As > 90% of INR measurements during the entire follow-up period were within the therapeutic range of INR 2.0 to 4.5, which is the lowest erratic INR ever published...
we conclude that low-intensity anticoagulation with a target INR of 2.0 to 3.5 is safe for patients with SJM prostheses in the aortic position as well as the mitral position.

my underline

In contrast to our findings, intention-to-treat analysis of two randomized
trials31,32 demonstrated a decrease in bleeding complications without an increase in embolic events with so-called low-dose rather than standard-dose oral anticoagulation.

I think that's some reasonable evidence

let me know (by PM for instance) if you want the PDF of the study

 

[JulienDu]

The problem is that there isn't any evidence that such a regimen is safe with other valves. This is a case where absence of evidence does not

I am not sure about that : ( many experienced AC guys will tell you that staying in the narrow 1.5-2.0 range is very hard )

-http://www.ncbi.nlm.nih.gov/pubmed/20598989 ( 1.5-2.5 and no aspirin)

-http://www.ncbi.nlm.nih.gov/pubmed/17890730 (1.8-2.8 and no aspirin)

-http://www.ncbi.nlm.nih.gov/pubmed/12970212 (1.8-2.8 and no aspirin)

-http://www.ncbi.nlm.nih.gov/pubmed/12918853 (1.5-2.5 and no aspirin )

 

[Silver Bullet]

Pellicle and JulienDu, my comments stand, since they refer to the absence of evidence supporting an INR goal of 1.5-2.0 with mechanical aortic valves other than On-X. Evidence that a range of 1.5-2.5 or 1.8-2.8 is acceptable is not the same as evidence that a goal of 1.5-2.0 is. A goal range of 1.5-2.0 is incredibly low, and does not at all overlap with traditional goal INR ranges for mechanical aortic valves. The other ranges studied in the referenced research all overlap with traditional goal INR ranges for mechanical aortic valves.

The other studies provided above certainly *raise the possibility* that an INR goal of 1.5-2.0 in low risk mechanical aortic valve patients may be acceptable with all bileaflet valves, not just the On-X valve. But it remains absolutely true that there is no evidence whatsoever that that target range actually is acceptable with any valve other than On-X. (As I mentioned, the evidence that that range is acceptable with the On-X valve is not the highest quality evidence, which would be *multiple* randomized trials with similar results, at least one of which is not funded by On-X, but what ya gonna do?)

It is noteworthy that the current guidelines (2014) of the American College of Cardiology recommend in INR goal of 2.5 for low risk patients with mechanical aortic valves plus the use of low dose ASA.

 

[W. Carter]

To my knowledge all of the newer valves are coated with pyrolitic carbon. I don't know why everyone is so fixated on a lower INR range. My range is 2.5-3.5 and I can't tell the difference between 2.0 and 3.5 when I cut myself. I'm quite happy with my INR at 3.5 or slightly higher at times. I don't feel any different. I have cut myself shaving and bled a little more than usual and think my numbers must be high to find out that they were actually lower than my range, so thats no test. It has to get over 5.0 for a person to really notice more bleeding from my experiences. I have been to 7.0 and thats no fun at all.

I'm not a Doctor but I would rather be slightly over medicated than under medicated when we're talking strokes from blood clots or having to replace a mechanical valve.

 

[pellicle]

Hi

Pellicle and JulienDu, my comments stand, since they refer to the absence of evidence supporting an INR goal of 1.5-2.0 with mechanical aortic valves other than On-X.

I don't quite understand what you mean "my comments stand" ... I understood, and I realised that the evidence was just that ... evidence. I realise too that the large and detailed study I cited only compiled compelling evidence in the down to the 2 range. It would require more study to see if the lower limit was lower or already found.

I'm trained in science and am primarily evidence driven, not "just what I was taught at University". I am evidence driven because as more evidence emerges "what we were taught" may prove to be inadequate or faulty.

It has been demonstrated many times in the history of science that people tend to "believe" what they wish, and that as fresh evidence emerges that contradicts older theory many older practitioners hang on to it. I am uninterested in debates on what's right and what's wrong. I'm only interested in looking for evidence.

Myself I have no real desire to move below INR=2 as an extended proposition because there is no evidence to suggest I'd be benefited in any significant way from remaining at my target INR = 2.5 What I also see is that there is usually an amount of wiggle in my INR graph despite consistency in all things (diet, exersize, weather dose) so this suggests to me that attempting to sit lower may indeed just result in my dipping below a safe lower bound and having a TIA or worse.

Best Wishes

 

[Silver Bullet]

... I don't know why everyone is so fixated on a lower INR range. My range is 2.5-3.5 and I can't tell the difference between 2.0 and 3.5 when I cut myself. I'm quite happy with my INR at 3.5 or slightly higher at times. I don't feel any different. I have cut myself shaving and bled a little more than usual and think my numbers must be high to find out that they were actually lower than my range, so thats no test. It has to get over 5.0 for a person to really notice more bleeding from my experiences. I have been to 7.0 and thats no fun at all.

I'm not a Doctor but I would rather be slightly over medicated than under medicated when we're talking strokes from blood clots or having to replace a mechanical valve.

Bleeding risk is clearly higher when the INR is higher, even within the 2-3.5 range. How you feel about it and how much you beed when you cut yourself is no way to determine whether that's true or not. Only randomized trials can show that and the data there is extremely consistent: bleeding risk is higher with higher INR's and higher INR goals. Period. Full stop.

Your last statement is a value statement with which I, and, I suspect, most people agree. If one is going to risk bleeding or thromboembolism, bleeding is probably the lesser evil, unless the bleeding is into your skull/brain.

 

[Silver Bullet]

I don't quite understand what you mean "my comments stand"

I was just indicating that the study you provided in no way impacted what I wrote and which you quoted, indicating that there is no direct evidence for any valve other than On-X that a goal INR of 1.5-2.0 is acceptable for low risk patients with AVR.

 

[Silver Bullet]

.when I am within the new lower range, all those little nicks and scraps you get on your lower legs from sticks and bushes and rocks while riding dont send little streams of blood down my leg. When I was in the middle to upper 2's, I would get little streams of blood running down into my sock fairly regularly. Now, those little scrapes and cuts dont seem to bleed anymore than they did before I was on the coumadin. Maybe its not quite a scientific observation, but its real life experience from some one in the same situation you will be in.

Can you wear something to protect you from getting all those little cuts? I'm not worried about bleeding per se, but if there's bleeding, then blood vessels are being opened, so if I were you, I'd be worried that they could serve as portals of entry for bacteria that could circulate in your blood stream and seed your prosthetic valve causing endocarditis. The risk of endocarditis is generally low after the first 6 months post op, but it's never zero, and the risk of dying if one gets prosthetic valve endocarditis is in the range of 30%. Something to think about ...

 

[COfireftr]

I got my OnX 3/2014 at age 42. Target range post-op was 2.5-3.5. After receiving the letter from OnX and delivering it to my cardio, my primary, and my nurse, I am approved for 1.5-2.0. My nurse and I (hey, i see her every 5 weeks, I trust her) keep my INR around 2.0-2.3. I was having a lot of bruising with above 3.0. I'm looking forward to following Europe's lead and doing low-dose aspirin only. But I'm not in a rush.

-Meredith

Thanks so much for sharing your personal experience. I am very excited to see what the future holds. I just wish I had the ability to wait another 10 years or so to see what that might be.

 

[COfireftr]

Thank you so much, Silver Bullet, for your feedback. It's great to have someone with your level of clinical experience while being a patient yourself. That provides great perspective and I can only imagine it is of great benefit to your patients.

As for your job, I think that you need to make the choice that's best for your health first, and worry about your job later. If I were you - a firefighter - my worry would be suffering head trauma while anti coagulated. That could be devastating. How often does your job result in a bonk on your noggin?

I understand and appreciate the logical choice is to look only at my health and worry about the rest later. But...I also have to consider my mental health and the well being of my family. This is my livelihood. Being forced out of the job I love for something I know would not impact my ability to perform is the frustration. There is so much misinformation about Coumadin and it is so frustrating that an occupational physician could have more influence than my personal Cardiologist and Cardio Thoracic Surgeon in determining my ability to function on this medication. This is all based on an outdated catch all medical document (NFPA 1582). My Cardiologist was dumbfounded that I may not be able to continue my employment. I honestly can't say I have ever taken a direct blow to my head while on the job. Not to mention, I always have a helmet on and am surrounded by medical professionals. I took more significant falls on my mountain bike yesterday than I have had in my entire career as a Firefighter or Paramedic. I feel the decreased INR could be my "in" to stay on the job and I feel the benefit outweighs the risk. Nevertheless, it is still a very tough decision that I can't take lightly, so will keep researching until the bitter end.

Thanks again,
Eric

 

[pellicle]

Hi

... that there is no direct evidence for any valve other than On-X that a goal INR of 1.5-2.0 is acceptable for low risk patients with AVR.

true, but then because the valve materials / manufacture / designs are so very close its reasonable to consider that there may be transferability of results, which of course is done in some study outcomes. Of course more study is needed, and as I said earlier the reasons for me to not want to be below 2 remain.

I think its reasonable to view that the current bi leaflet pyrolytic carbon St Jude and the ATS/Medtronics valves (which are so close in design that patents are almost ridiculous) would perform similarly to On-X. Again there I agree that there is no "direct evidence" but sometimes it gets to the point where the evidence gathered in one area can be reasonably transferred to another.

The GELIA study has shown that the previous AC regime is set too high and that it can be brought down. I believe that the next step is to await studies where they repeat the studies done on the On-X across other valves. The potential for benefits in patient outcomes are too significant for this to remain un-researched for longer.

 

[JulienDu]

I was just indicating that the study you provided in no way impacted what I wrote and which you quoted, indicating that there is no direct evidence for any valve other than On-X that a goal INR of 1.5-2.0 is acceptable for low risk patients with AVR.

I am not a scientist and I do not have an education backgournd but the thing is you can look at those studies done on any other bi-leaflets valve and not specific to one type of valves.

- http://www.ncbi.nlm.nih.gov/pubmed/17890730

1327 patients with no aspirin and target INR of 1.8-2.8. "The incidence of bleeding events that required hospital admission was 1.42%" The incidence of thrombo-embolic events that required hospital admission was 0.19%"

- http://www.ncbi.nlm.nih.gov/pubmed/12970212

908 patients with no aspirin with target INR of 1.8-2.8 "The linearized thromboembolism rate (% per patient year) was 0.21% for both groups "The bleeding complication rate was 0.56% in the low-dose regimen group"

In the Onyx Study http://www.ncbi.nlm.nih.gov/pubmed/20598989 :

190 patients with aspirin with target INR of 1.5-2.0. Major bleeding events was 1.48%.

------

So when I see that, I see 2 things.

1-Studies done on other valves with 1.8-2.8 and no aspirin show bleeding event are similar or inferior to Onyx 1.5-2.0 with aspirin

2-You are right Onyx is the only valve one that has pushed the field of tests so far and has proved that we can safely stay at a low INR and we can all admit that this is serving the whole valve community.

And I am not even mentioning the results with the ATS valve that showed incredible results at 1.5-2.5 ( http://www.ncbi.nlm.nih.gov/pubmed/12918853 ). They explained that by both the pyrolic carbon plus a specific open pivot system that "have no recesses or cavities where a potential thrombus can form. While cavity pivots rely on mechanical sweeping and high-velocity leakage jets, with the Open Pivot design, the unimpeded flow of blood provides for a continuous passive washing."

the risk of endocarditis is generally low after the first 6 months post op

Why is it higher during the first 6 months ?

 

[Silver Bullet]

JulienDu:

1) I agree that there are good reasons to *speculate* that all modern bileaflet mechanical prostheses in the aortic position of low risk patients may do well with an INR range of 1.5-2.0, but until evidence directly testing that hypothesis becomes available for those other valves (other than On-X), all one can do is speculate. The history of medicine is replete with instances where what should be true has turned out to be false when properly tested by randomized trials (http://www.mayoclinicproceedings.org...32464/mmc2.pdf). There is a reason why the current (2014) guidelines of the American College of Cardiology recommend an INR range of 2-3 under these circumstances. The evidence upon which to make any lower recommendations *just isn't there*. I don't even think that the PROACT trial is good enough evidence to warrant a guideline recommendation for On-X valve recipients to aim for an INR of 1.5-2.0. Why? Again, because it's only one small randomized trial that is funded by the manufacturer of that valve. If I received an On-X valve, I would take ASA and aim for an INR of 2-2.5. I wouldn't sweat it if my INR dipped below 2 from time to time, but I would only intentionally aim for an INR of 1.5-2.0 if I had bleeding problems in the former range. I would not aim for an INR of 1.5-2.0 right off the bat because I don't think that one small industry funded study is enough to change practice (even though it may be enough to convince the FDA to approve the valve under those circumstances). Having said all of that, I would have preferred to have an On-X valve because I think that the available evidence does provide those with an On-X valve with a little bit more confidence when facing lower target INR values as an option.

2) This risk of IE is highest in the first 6-12 months post op probably because of the presence of organisms that seed the prosthesis intraoperatively and because the body's endothelial cell lining is not completely in place over suture lines and other foreign materials that microbes can more easily adhere to.

 

[JulienDu]

1) Having said all of that, I would have preferred to have an On-X valve because I think that the available evidence does provide those with an On-X valve with a little bit more confidence when facing lower target INR values as an option.

My first choice was also Onyx but not because of the lower INR, cause as I mention before in those studies, it did not prove any concrete improvement in term of less chance of bleeding. I did not chose Onyx for its "best performance" because as I mention before, their marketing is wrong, on their website they do compare their valve with older generations. I chose Onyx because of the Pannus Barrier, I liked the idea to have something that could help slow or prevent an event that I had no control over (even though the valve is too new, like the regent to prove anything about pannus yet) .

My surgeon did agree with all this and said he would put me an Onyx unless the St Jude would fit better or the Onyx would be too small. I ended having a St Jude like you. I was wondering what happens for you ? Your first choice was also an Onyx but you ended up having a St jude. Why ? and I see you are from Canada, where did you get this done ?

2) This risk of IE is highest in the first 6-12 months post op probably because of the presence of organisms that seed the prosthesis intraoperatively and because the body's endothelial cell lining is not completely in place over suture lines and other foreign materials that microbes can more easily adhere to.

Ok, thanks for the explanation.

 

[Silver Bullet]

My first choice was also Onyx but not because of the lower INR, cause as I mention before in those studies, it did not prove any concrete improvement in term of less chance of bleeding...

... Your first choice was also an Onyx but you ended up having a St jude. Why ? and I see you are from Canada, where did you get this done ?.

I agree that the PROACT trial didn't concretely prove that an INR goal of 1.5-2.0 is safe and associated with less bleeding even though that one trial showed exactly that. The problem is that it's just one trial that is sponsored by the manufacturer. Nevertheless, the PROACT trial shouldn't be ignored. If a low risk patient with an On-X valve experiences bleeding (say a spontaneous subdural hemorrhage) with INR in the recommended range of 2-3, especially if it happens with INR 2-2.5, then it is perfectly reasonable to aim for an INR of 1.5-2.0 and feel relatively comfortable about it. I don't think you can say that for any other valve out there.

I didn't end up with an On-X valve because I needed a Bentall procedure rather than just an AVR and it turns out that Toronto General Hospital doesn't stock the On-X valve with attached conduit. They only carry the On-X valve alone. So I got a St. Jude valve that has a dacron conduit attached that acts as a replacement for my aortic root and proximal ascending aorta. My surgeon said that this design implies that I should not have to worry about pannus growth in the future.