Efficacy and Safety of Very Low-Dose Self-Management

[Marc]

Hi Friends!

Here I found an interesting article regarding the mid term results of the escat III study (Efficacy and Safety of Very Low-Dose Self-Management of Oral Anticoagulation in Patients With Mechanical Heart Valve Replacement).

For those of you, that have direct access to ats or to a library that supports access to ats, thats the abstract (for all):
http://ats.ctsnetjournals.org/cgi/content/short/90/5/1487?rss=1

Best wishes!
Marc

 

[dick0236]

I have been thru just about all the INR or Pro-Time testing protocols over the years. My own experience has been that if I take my coumadin/wararin(or whatever they call anti-coagulant in your country) as prescribed and test on a regular basis...I have had few problems with maintaining a correct INR (my case 2.5-3.5). In my case, warfarin has been a very predictable drug....but it is a drug that you cannot "screw around with".

 

[Protimenow]

I don't understand their use of the term 'very low dose.' Varying medications require varying doses -- some are just more powerful than others. The paper's title is somewhat deceptive - to me, it sounded like they were testing dosages lower than what are normally prescribed. The dosages -- from roughly 1 mg (or is it mcg?) to maybe 10-12 for some who are very resistant to warfarin are APPROPRIATE doses -- whether it's micrograms or grams, it shouldn't matter -- low, very low, or even high are all relative. The point of this study was to reaffirm that patient self testing (this study had patients do weekly tests) and management (it's not clear in the abstract whether the patients self-managed their doses or not) can help to keep the INRs in range, and reduce negative events.

This is something that many of us who self-test and self-manage already know -- but it's good to have it reported in another journal. This is just one more weapon against insurance companies and stubborn doctors who refuse to allow the patient to self-test (and, in many cases, to self-manage), because they don't think we can do it (and most of us CAN).

 

[normofthenorth]

I don't understand their use of the term 'very low dose.' Varying medications require varying doses -- some are just more powerful than others. The paper's title is somewhat deceptive - to me, it sounded like they were testing dosages lower than what are normally prescribed. The dosages -- from roughly 1 mg (or is it mcg?) to maybe 10-12 for some who are very resistant to warfarin are APPROPRIATE doses -- whether it's micrograms or grams, it shouldn't matter -- low, very low, or even high are all relative. The point of this study was to reaffirm that patient self testing (this study had patients do weekly tests) and management (it's not clear in the abstract whether the patients self-managed their doses or not) can help to keep the INRs in range, and reduce negative events.

This is something that many of us who self-test and self-manage already know -- but it's good to have it reported in another journal. This is just one more weapon against insurance companies and stubborn doctors who refuse to allow the patient to self-test (and, in many cases, to self-manage), because they don't think we can do it (and most of us CAN).

Protimenow, I think their target doses ARE lower than usually prescribed for mech-valve patients. And especially after they ratcheted them down another notch, like INR=1.6-to-2.1 for an AVR!! I'd be interested to know if they're using one of the mech valves that makes (or implies) special low-INR claims, like the On-X or the ATS, or if it's an older more standard design. It's not nuts to predict that a more stably maintained INR could work well at a lower target level than one that's more like a roller coaster. Seems to me that's where this study is headed.

 

[Marc]

Protimenow, I think their target doses ARE lower than usually prescribed for mech-valve patients. And especially after they ratcheted them down another notch, like INR=1.6-to-2.1 for an AVR!! I'd be interested to know if they're using one of the mech valves that makes (or implies) special low-INR claims, like the On-X or the ATS, or if it's an older more standard design. It's not nuts to predict that a more stably maintained INR could work well at a lower target level than one that's more like a roller coaster. Seems to me that's where this study is headed.

Yes you are right! They checked doses that result in very low INRs. The study was done with sjm-valves only. There are two former studies called ESCAT I and ESCAT II, the one I posted is the mid-term of ESCAT III.

Here you can find some more informations: http://www.ismaap.org/index.php?id=595

Best wishes,
Marc

 

[Bina]

Hello Marc,
I have a St. Jude Regent valve and home test....mit ein Coaguchek XS, naturlich....My INR is very stable and
lately I am happy to leave it at the lower end of my range. Last test was 2.7 and I take only 17 mg per week.
Thank you for posting this study

 

[Protimenow]

OK. Now I think I get it. It's not that the amount of anticoagulation is changed -- it's a new formulation of warfarin that is available in what they're calling 'very low dose.' So instead of the 51 I take weekly, perhaps I'll only need 25 of the very low dose medication. I'm wondering of this new 'very low dose' warfarin is something that the drug companies can get a patent on - and squeeze out those of us who pay a dime a day or so for generics. As far as I'm concerned, I'm okay with taking two pills a day and paying a dime or two and would have to think twice about a patented 'very low dose' version that'll probably cost $1 or so a day.

 

[dick0236]

would have to think twice about a patented 'very low dose' version that'll probably cost $1 or so a day.

Probably be more like $5 or $10 per day or even $30 per day....or more! In the early '80s, before the DuPont patent ran out on Coumadin, I paid $100/mo for 30 Coumadin tablets....and $100 was worth a lot more in the '80s than in todays dollars, or pounds, or any other currency. I think I will also stick with my good 'ole warfarin.

 

[catwoman]

Because I don't have an ATS subscription, I can't view the entire article.
However, from what I read, I interpret the article to be a review of a study showing the safety of lower-than-normal INRs, which in turn are derived from lower-than-normal warfarin dosages -- not based on using yet another new anticoagulant. (Not sure what the generic or tradename is for warfarin in Germany, where it appears the study sas done.)
I would have to see quite a few more of studies like this before I redo my INR range and, of course, dosage.
If it ain't broke, no need to fix it.

 

[Bina]

OK. Now I think I get it. It's not that the amount of anticoagulation is changed -- it's a new formulation of warfarin that is available in what they're calling 'very low dose.' So instead of the 51 I take weekly, perhaps I'll only need 25 of the very low dose medication. I'm wondering of this new 'very low dose' warfarin is something that the drug companies can get a patent on - and squeeze out those of us who pay a dime a day or so for generics. As far as I'm concerned, I'm okay with taking two pills a day and paying a dime or two and would have to think twice about a patented 'very low dose' version that'll probably cost $1 or so a day.

Nope. Same old reliable warfarin/Coumadin med, just a lower target INR range -for home testers only- who can
keep ontop of their INR readings. Much like the new INR ranges being touted in California.
It's a worthwhile method for hometesters like myself with super stable INRs and eating habits.
The reasoning behind this range is NOTHING to do with the cost of meds, but everything to do with keeping the
risk of higher INRs and bleeding risks at a minimum.

 

[Protimenow]

Quoting the article that the link was posted for, it says: "Two very low dose groups received a new very-low-dose anticoagulation with a target INR range of 1.6 - 2.1 for aortic valve replacement and 2.0 - 2.5 for mitral or double valve replacement. " To me, this means, to me, like there's a new very low dose anticoagulant. I can't see how reducing our dose of good ol' fashioned warfarin could do anything other than move our INRs dangerously close to 1.0.

I've found, monitoring my own INR, that decreasing my warfarin dosage DOES reduce my INR. If lowering the therapeutic range was what was being tested, I'm assuming that there's a LOTof clinical research that established the safe range for those taking warfarin.

 

[normofthenorth]

Protimenow, isn't "a target INR range of 1.6 - 2.1 for aortic valve replacement" much lower than your target INR range? Maybe it's "dangerously close to 1.0" and maybe it isn't, but following up on the patients to see whether they're in any more danger than you folks with higher INR targets is the standard scientific-method way of finding out. The dose is only lower because the target is lower, as several others have said. And the target can be lower (maybe) because home-testing and -management may give better control.

E.g., if it were seriously dangerous for a mech AVR patient to go below INR = 1.6 even for a few days, then a standard patient (tested in a clinic every week or two) should have a target around 2.5 or higher, to give some safety margin. (That's also how we design bridges, airplanes, car parts, etc.) OTOH, if home management can reliably keep a patient's INR within the actual target range, then a lower target will be safe enough against clotting, and much safer against bleeding. That would be better, right?

 

[Marc]

The study goes not along with any new anticoagulant! They just reduced the dose, to get a lower INR and showed, that this lower INR does not increase any risk. In Germany we use Phenprocoumon (Marcumar: http://en.wikipedia.org/wiki/Phenprocoumon ), so the study was done with that and with (actual generation) sjm valves only. It is exactly as Bina explained it: "...just a lower target INR range -for home testers only- who can
keep ontop of their INR readings". I am sorry, that I can not post you the full article, a few weeks ago it was free to be read on the net. Because at the moment the study is in the mid-term phase, one should wait until its end before even thinking about lowering his/her personal INR-range. But one should keep that study (the most established one regarding low dose anticoagulation) in mind.

 

[dick0236]

Because at the moment the study is in the mid-term phase, one should wait until its end before even thinking about lowering his/her personal INR-range. But one should keep that study (the most estblished one regarding low dose anticoagulation) in mind.

Your partial quote, above, contains the important caveat before thinking about reducing a mechanical valve anticoagulant. I suffered a stroke, many years ago, due to letting my INR fall to "near normal"??....as a result, I became PERMANENTLY 50% BLIND. I have had very few problems while keeping my INR around 3.0....and there are NO circumstances where I would permit a doctor to reduce me to around 2.0, or below. I understand that newer valves normally require less anti-coagulant, but a properly managed higher INR allows for a margin of error.

 

[catwoman]

The study goes not along with any new anticoagulant! They just reduced the dose, to get a lower INR and showed, that this lower INR does not increase any risk. In Germany we use Phenprocoumon (Marcumar: http://en.wikipedia.org/wiki/Phenprocoumon ), so the study was done with that and with (actual generation) sjm valves only. It is exactly as Bina explained it: "...just a lower target INR range -for home testers only- who can
keep ontop of their INR readings". I am sorry, that I can not post you the full article, a few weeks ago it was free to be read on the net. Because at the moment the study is in the mid-term phase, one should wait until its end before even thinking about lowering his/her personal INR-range. But one should keep that study (the most established one regarding low dose anticoagulation) in mind.

I agree with Marc and Bina -- it's based on a study showing a lowered dose of anticoagulation, not a new anticoagulant.
Would like to have read the full article, but I don't want to shell out $25US just for 24 hours' use to read one article.
Medical articles are written by medical professionals; copy editors go over the text before release. However, the copy editors probably have more training in writing for medical purposes than for the masses.

 

[Protimenow]

Like the others, I don't have access to the full article. The words 'new very-low-dose anticoagulant' certainly READ like the anticoagulant used for one group was different from the warfarin that has been in use for decades.

As far as lowering the target range -- as others have said, this is probably for certain valves that manufacturers claim aren't as prone to clot formation. I'm certain that there's a wealth of research out there that established the target ranges for earlier mechanical valves -- and I don't think that this new research (even if it's using 'standard' warfarin and not the 'very-low'dose anticoagulant' mentioned in the paper) will have a lot to do with lowering the range for people with the older valves.

FWIW -- my INR dropped to around 1.6 or so a few times while I've self-tested and I didn't panic or run out for Lovenox - and it didn't kill me. There was a time when I wasn't being regularly tested when I developed what looked like a facial 'wart' that dissolved when I increased my warfarin dose (I'm guessing it was a clot that formed in my face, instead of lungs and brain) - but I don't know what my INR was during that period. While it may not always be life threatening to drop below range, it's simple enough for many/most self-testers to stay within range, even if the lower limits may be proven to be somewhat higher than necessary for some newer valves. (And if newer valves require a lower range, it shouldn't be that difficult for self testers to stay within that range).

After re-reading the abstract another time, I took away a couple things:

Self-testers tested weekly (in the low-dose group) or twice a week (in the very-low-dose group)
Negative events were slightly (perhaps not significantly) lower in the very-low-dose group (with twice weekly testing) than in the low dose group.

This suggests that more frequent testing - which can probably best be done by the patient, with his or her own meter - enables better control of INRs and makes maintaining a lower INR safer than the former methods of infrequent lab testing. It may be the MORE FREQUENT testing that makes the lower range safe.

(In a situation where a person's INR is 'stable', shifts out of range may occur and be undetected and untreated - potentially putting the person at risk of adverse events, if infrequent testing is done)

This suggests the obvious -- more frequent testing (once or twice weekly) will enable anyone on anticoagulants to do a better job of staying in range (as long as no major shifts that can start the roller coaster are made).