What is the definition of Cumulative Risk With Coumadin?

[ALCapshaw2]

Here is a copy of the Risk Analysis by Bradley White which appeared in the thread entitled "I'm only 24" beginning February 13, 2007 in the Valve Selection Forum. This post was #35 in that interesting but lengthy discussion of this same subject. FWIW, I have examined the mathematical analysis and conclude that the mathematics is Correct given the *assumption* that the Annual Risk is constant. Bradley compiled these statistics assuming 1%, 2% and 3% annual risk factors.

One point that needs to be emphasized, especially to newcomers to anti-coagulation, is that there was a MAJOR improvement in anti-coagulation management in the early 1990's when Testing went from the Old Prothrombin Time Test (using highly variable reagents) to the International Normalized Ratio (INR) test which compares clotting time to that of a calibrated standard (i.e. a RATIO which cancels out the reagent variability). Finger Stick Testers and Home Testing have Revolutionized INR Testing, greatly reducing the incidence of Major Bleeding (or Stroke) from the previous decades.

'AL Capshaw'

The following was written by Bradley White:

I cannot stress that when risk for ACT complications is given on a "per annum" basis it is not to be taken as cumulative. This is true of any statistic which is laid out as "the risk per patient year is X%". This is a quite basic principle in all biological sciences, especially medicine. I find it astounding that any surgeon would try to say the risk is cumulative!!!! It just makes no sense.
Scary how little medical professionels understand about basic statistics.

If risk were cumulative then that would imply at a risk rate of 3% at 35 years of anti-coagulation the risk would be greater than 100%. This simply isn't true or possible, it is not how statistics works. These risk events are always observed in patient years, one could not reasonable extract that data and attempt to add it up and say that after 35 years everyone would have had an event. That's simply not how statistics works. Anything whose risk is finite in a per year basis will never be 100% over any course of time. It will approach 100% but never reach it.

The cumulative nature of anti-coagulation risk is that every year there is a 3% risk. That means that every year there is a 97% chance of not having an event. As time goes on the chances that you won't have experienced an event decrease due to the recurring risk of 3% per year. You can calculate this risk by taking .97 and using the amount of years you are interested in as the exponent and then subtracting that number from 1 to figure out your chances of HAVING an event in X years:

I have made the following calculations based on a 1%, 2%, and 3% risk at 10 thrugh 50 years. The number represents the chances that you WOULD experience an event by this year if you were on ACT for mechanical valve.

AT THE 1% RISK LEVEL

10 YEARS = 9.6%

20 YEARS = 18.2%

30 YEARS = 26%

40 YEARS = 33.1%

50 YEARS = 39.5%

AT THE 2% RISK LEVEL

10 YEARS = 18.3%

20 YEARS = 33.2%

30 YEARS = 45.5%

40 YEARS = 55.4%

50 YEARS = 63.6%

AT THE 3% RISK LEVEL

10 YEARS = 26.2%

20 YEARS = 45.6%

30 YEARS = 59.9%

40 YEARS = 70.4%

50 YEARS = 78.2%

If anyone doesn't understand how I calculated those risks I can send them the excel file. The thing that stands out the most is the huge long term risk change when one goes from a 1% per annum event rate to a 3% per annum event rate. At 30 years, less than half of those at 3% per annum event rate will have not experienced an event, while at the 1% per annum event rate 74% of individuals should not have experience an event. This a significant reduction in the long term risk of anti-coagulation and represents the major medical reason why self-testing is such a huge advance since it has been shown to decrease the event rate from the 2-3% per annum category to around 1% per annum.

Trust me surgeons and doctors are not infallible, especially when it comes to math. I teach pre-med students a 300-level Fundamentals of Genetics course (decent working knowledge of statistics) at Nortre Dame and it scares me to death to think that some of them could one day be my doctor based on their complete incomprehension of statistics (among other things) at this point in their eduction.

Brad
__________________
Ross Procedure, Dr. Quintessenza, All Children's Hospital, St. Petersburg, FL -- 9/12/2000

Aortic Root and Valve Replacement with 23 mm Homograft, Dr. Joseph Dearani, Mayo Clinic, Rochester, MN -- 12/7/2006

 

[Karlynn]

(Ross, maybe you should move these posts on the "cumulative" discussion to it's own thread. It's kind of hijacking Harleygirl's thread (even though it does directly relate to part of her post), but I think it's an important discussion and one that continues to be rehashed and disputed time and again. HG's decision has been made, and I don't want her to feel that this discussion is an effort to try and persuade her.)

I have a problem with Brad's post, not because it's wrong, but because many people don't understand statistics and see it as proof that risk is cumulative and at a pretty alarming rate. Many of us are not left-brained. If Brad set it to lyrics and music, I'd probably would have had a much easier time understanding it initially. Many people, like me who just aren't good at math, look at it, go and don't take the time to figure out the meaning, but are just alarmed by the numbers and don't sit and read and reread (like I did) to understand it. (I envy those of you who are mathematically inclined at these times.)

To put it in a way that people like me can understand - you can do the same risk assessment with driving a car. At year one you have X% of a chance of having an accident. Each year you have that same X%, but considering that you're going to be driving a long time, by year 30 the chances are pretty good that at some point within those 30 years you will have had an accident.

The big unknown with both "events" and "accidents" is - how are they defined. Is an accident one where you total your car or lose your life, or an event one that requires a transfusion or you bleed to death? Or is an accident hitting someone's bumper in a parking lot or an event cutting your finger while chopping carrots? How you interpret the meaning of these two words has a great deal of impact on how you view the importance of the numbers. It can be the difference between and (For those who know the old joke - it reminds me of the punchline where the accountant, when asked: What is 2 +2?, answers: What would you like it to be? It's subjective for each person.)

The bottom line is - for those who are leaning towards a tissue valve, they will probably choose to interpret the numbers in a much worse light than someone who is leaning towards a mechanical. And the same for resurgery, those leaning towards mechanical will probably place much more emphasis on the repeat surgery risk than someone choosing tissue.

The reality is, we have very few pre-surgery members join who don't have a clue what they want. Most are pretty sure and come here for verification that their fears of the one they don't think they want are well-founded and their reasons for choosing the other are well-supported. I think it's in our community's best interest to not cause any member to be fearful of any choice because we all know that there are times where the valve you choose pre-surgery isn't the valve you come out with.

 

[Ross]

Susans post is number one and she is technically the thread starter. I cannot edit the other thread without all of this falling in chronological order no matter what I do, so please cut me some slack.

 

[tobagotwo]

The risks of warfarin are not cumulative, but are relatively steady. They do increase slightly with age, relative to the risks of biological valves, mostly due to the naturally increasing fragility of some people's intercranial and alimentary blood vessels. But it's not much of an increase, and not for everyone - it's in the genes. I feel it's not enough that it should raise your level of concern.

The risks of multiple reoperations are slightly greater in younger people than the risks of Coumadin, because of the increased number of resurgeries that may be required over a lifetime.

So, at 41, if you choose a biological valve, you begin with a slightly greater risk than the 41-year-old next to you who received a mechanical valve. At 65, your tissue valve would give you a slightly lower risk than the 65-year-old next to you with the pyrolytic carbon model.

To quote Frost, "..though as for that, the passing there had worn them nearly both the same."

So who dies earlier? The unlucky ones, the ones with greater heart damage, and the genetically challenged. The statistics seem to show the life expectancy being about a wash for either choice, most other factors considered.

I would note that I have not seen anything (science) that would lead me to believe that a 41-year-old should expect 20 years out of any biological valve at this time. Likely not 15 years, either. I would entirely expect a reoperation in your early fifties, and another down the road near 70.

Note that the statements above are not implying that you should go either direction. They're simply to put likelihoods on the table, as I see them. You need to determine for yourself which sullen companion you will be able to live with best - the knife or the pill.

Best wishes,

 

[tobagotwo]

I had a PM with a similar take on what I wrote, so I'm going to borrow from my reply to help respond here.

No, what I wrote doesn't support the "cumulative" statement about warfarin risk. I can disagree with an expert's statement because the writer is a doctor, not a statistician. He knows his medicine, but is less persuasive with his math. Several excellent statisticians on the site have debunked the cumulative risk statement quite convincingly - on principles of math, not a leaning toward one valve type or another.

It's also not borne out in the numbers. He says that there is a greater risk when one is over 65, and I agree. However, he describes it as cumulative, meaning it builds via addition over time. I disagree, and attribute the added risk to easily noted changes in the aging human condition, largely in the increasing fragility of the intercranial, alimentary, and other blood vessels, that are more a slower, straighter line rise in risk.

If it were truly cumulative, starting around 60 or so, the difference in death rates would be quite significant with age, advancing up into an alarming incline (remember, it has to be an increase on top of the general death rate to qualify as added risk). Everyone who favors tissue valves would be pointing to that graph and saying, "See? If you're on Coumadin, that's what will happen to you." But they're not. Because there is no such graph.

Instead, it appears to be only a slight rise in relative risk that increases quite slowly with age and eventually plateaus in the absence of comorbid factors. It's measurable, but not enough to be of great concern, especially when taken over the total range of risk over a lifetime, including the earlier risks avoided. It is, after all, risk over time, and it balances over a lifetime.

I would point out that "being over 65, high blood pressure, cerebrovascular disease, severe heart disease, renal insufficiency, and cancer" are increased risk factors for everyone in every case, warfarin entirely aside.

I'm predisposed to tissue valves for myself. Have been from the start. For me, it's a quality of life issue. I've chronicled many of my personal concerns about warfarin over the years. There are a number of things that go along with Coumadin use that I would have great difficulty dealing with, not the least of which is dealing with so much of the medical community from a large disadvantage. But some things that disturb me greatly don't bother some others. Again, the risks over time are the same, so the considerations can be more encompassing of the valve recipient's personality.

And it's plain that mechanical valves do work for those who choose to go that route. One of my main concerns is the raised risk of multiple operations with warfarin. But look at RCB. He is the personification of multiple operations and long-term warfarin use. How can you argue the warfarin point with someone who's been through all that and is still here to argue back?

You may have a hard time with your OHS, and be horrified that you will have to go through it again some time in your future. You may have an easy time, and decry yourself for having signed up for a lifetime of pills and blood tests. You must determine to be unsympathetic to yourself after OHS about your choice. You must simply accept that you made the best choice you could divine, and move ahead into the life given back to you.

We presuppose no comorbid conditions (other current illnesses) for this discussion. The life expectancy numbers after age 40 or so are so similar, that it boils down to how you like to take your risk. You can have the smaller, more continuous risks and impositions of Coumadin, or the higher, but infrequent, punctuating risks of reop, with nearly nonexistent risk in between. It's all in how you like to take the dose.

I had written this earlier (and better), but it didn't post, and was unrecoverable. Now it's late, I'm grumpy and frustrated, and I feel it's missing some points I had made before. And it really needs to be edited. But I'm going to post anyway, to get the main points out. Please forgive its unpolished state, and I hope I didn't miss any major gaffes.

Best wishes,

 

[dick0236]

These posts are getting pretty silly. I guess I ought to just go get my buffalo rifle and put me out of my misery before something REALLLLLLY bad happens. I fit into all the bad time lines that you folks are beatin' to death.
I am 71 (almost 72)
I have been on warfarin ACT continously for 40+ years
I had a CVA (cardiovascular accident) seven years after surger at age 38 that may or may not have been caused by warfarin.

However,
I do what I want, eat what I want, drink what I want (no alcohol anymore...by my choice) whenever I want.
My Cardio, during my bi-annual checkup three months ago, told me I was a "medical miracle". I disagreed and reminded him that my surgeon told me the valve would last 50 years. I got 9 years and 8 months to go.
I never had a choice about which valve I wantet, but.........
Obviously, if I had it to do over, I would be very foolish not to do it the same way.

These "my valve is best" wars are entertaining for awhile but then they get stupid. There obviously is a time and place for both valve types. Youse has your druthers and youse takes your picks..... There is NO silver bullet.

If you are "in the waiting room for OHS" this is a good source of information but there is also some misinformation. Your situation and circumstance is best known by you and your cardiac team. My experience, past and present, is that my docs have been a great help over the years.

 

[Nancy]

No matter what--life is finite. None of us will get out of this dying thing.

My husband had mechanical valves. He died at age 75. He outlived many of his high school classmates, in spite of his multiple co-morbidities.

Even though he had mechanicals, he still had to have 3 valve surgeries over his lifetime.

He was as tough as they come when faced with medical problems, and that was probably the main factor in his being able to live as long as he did with his multiple problems. He was completely unafraid of having any kind of medical intervention. Some of his classmates needed heart surgery of one kind or another and were scared. They never got the help they should have gotten. They just dropped over.

In the end, Joe had multiple organ failure, but his heart stayed strong to the last second.

I like what Bob has said, and his quote," To quote Frost, '..though as for that, the passing there had worn them nearly both the same.' "

My own feeling is the main factor in living long is to get the help you need when you need it, take no prisoners, and take no bull. Seek out the best doctors you can find and just get it done.

And respect your body, the place you live in.

 

[geebee]

Susan,

I do not believe any of the posts in reply to your original post were meant to attack you or were directed at you personally . The posts were merely disagreeing with the information put out in the article you reprinted. If I reprinted an article that stated the world is flat or there is no necessity for valve replacement surgery, I would think I would receive similar replies. Granted my examples are extremes but I think the point is well made. Just because an article is published by a well respected institution or person does not necessarily make it true. There have been many scientific statements that have proven to be false.

Considering all the posts about our disagreeing with cumulative risks of coumadin, you have to have considered there would be objections raised to your post.

I have been on coumadin for 27 years and do not, for one tiny second, think I am in any more danger than I was 27 years ago. My lifestyle is no different from my friends not on coumadin except, perhaps, I have more respect for my life and try not to squander the gift I have been given.

I hope for your sake you will not have to go on coumadin again. I would not wish it on anyone but I would tell anyone not to fear it or any risks that might exist. Live your life, stay healthy and all will be good.

 

[Bridgette]

I had no choice but to get a mechanical valve and go on Warfarin for life.
I also have intermittent AF and would have to be on it anyway so saw no point in getting a tissue valve and therefore needing another OHS in ten or so years time....everyone's situation is different but there are probably plenty of people watching/reading this site who are on Warfarin through necessity not choice.
Personally, I just try to see the positives in the drug - it really can be defined as a life saving medication, can't it?

I just wish people would STOP continually posting negative things about it - yeah we all know that there are things that we need to be careful about in relation to Warfarin - these facts are well known and publicised.
Why keep hammering this stuff about "cumulative risks" etc etc - remember that there are many on this site, who, like me, didn't have a choice and to be continually seeing the same old misinformation posted again and again is just very depressing

If you have the Ross Procedure, a tissue valve, repair or whatever - good luck to you - be happy with your choice and leave the posting of Warfarin info up to the people who have experience with it and therefore know what they are talking about.

I'll probably get slammed for posting this message.

 

[Ross]

I beleive this is the theory from which all else is derived. http://www.isixsigma.com/dictionary/Kaplan-Meier-780.htm

http://www.bmj.com/cgi/content/full/317/7172/1572