On-X trial for warfarin alternative treatment

[Keithl]

I received a Lerner in the mail for a new trial for On-X aortic valve folks to,try an alternative to warfarin. Did anyone else receive this? Sound interesting, bit not sure a possible twice daily pill is better than warfarin.

PROACT Xa - A Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely on Apixaban - Full Text View - ClinicalTrials.gov

PROACT Xa - A Trial to Determine if Participants With an On-X Aortic Valve Can be Maintained Safely on Apixaban - Full Text View.

www.clinicaltrials.gov

 

[DDT77]

I just received one as well. Wife handed it to me and I said, "damn - recall notice". Not a kind look in return...

Just looked at Apixaban price. Twice daily? Is study funded by BMS? Duke is chairing the study, and just had annual checkup there but a month ago. No study query from their side.

Good study for those that are Warfarin contraindicated. Unclear possible benefit for those who manage Warfarin well. I'll pass on enabling the marketing people from profiting on Warfarin fear.

 

[ATHENS1964]

Please keep us informed .

 

[pellicle]

Let's hope this goes better than the last one.

Personally I like the devil I know

 

[Keithl]

i am going to reach out to get some info, but am very fine with warfarin and my blood tests.

 

[vitdoc]

It will be interesting to see how they sell this to get people in the trial. It probably would be that life would be easier without INR testing. That might bias the type of patient to those that have issues with their INR. The study aims for a 2-3 INR with monthly testing plus low dose ASA presumably for both groups. They are looking for various thrombotic events and bleeding events. If the study works out the OnX valve people will have another marketing tool.
Personally if I had an OnX valve I would let someone else do this study.
Not to keen on stokes.

 

[jlcsn2015]

Interesting, i have not received any messages from On-X

 

[ATHENS1964]

CryoLife Initiates Enrollment in PROACT Xa Clinical Trial | Cryolife Inc.

investors.cryolife.com

 

[pellicle]

Not to keen on stoke

Well at least this time its not just aspirin. Xa anticoagulants are around just not approved for valves.

 

[pellicle]

I thought I'd do another dig, last time I never kept notes, but that was 2012 and I was simply curious. I was however strongly left with the impression of:

we've spent a ton of reserarch money on this stuff for a problem which boils down to "patients can't be trusted" and found that only when you slant the deck is Xa better than Warfarin.

Eg from Bleeding with Direct Oral Anticoagulants vs Warfarin: Clinical Experience

The vitamin K antagonists (VKAs), such as warfarin, have been the standard and indeed, only, option for oral anticoagulant therapy for decades. However, their use requires routine coagulation monitoring because genetic variation and interactions between warfarin and diet, other drugs, and comorbidities produce variable and unpredictable anticoagulant effects. [PE: lets throw around a bunch of reasons which are often not related to the need for regular measurement and just keep painting regular measurement as "Dr Evil" ]1, 2, 3 The time in therapeutic range is a determinant of the efficacy and safety of warfarin [PE: no **** Sherlock].4 In 1 representative study, 62% of warfarin-treated patients with nonvalvular atrial fibrillation (NVAF) who were admitted to the emergency department for ischemic strokes had international normalized ratios (INRs) that were outside of the desired therapeutic range [PE: so in ONE study from 2008 they found that strokes happened outside theraputic range ... I'm betting this was INR lower than theraputic ]

It goes on in a similar vein
rates of major bleeding were 3.11% per year in the dabigatran 150-mg-twice-daily group (relative risk 0.93; 95% confidence interval [CI], 0.81-1.07; P = .31) and 2.71% per year in the dabigatran 110-mg-twice-daily group (relative risk 0.80; 95% CI, 0.69-0.93; P = .003) vs 3.36% per year in the warfarin group

wow ... that much ... worth noting in the study they cited for warfarin: https://www.nejm.org/doi/full/10.1056/NEJMoa0905561

... with the INR measured at least monthly. ... In the warfarin group, the mean percentage of the study period during which the INR was within the therapeutic range was 64%.

so pretty miserable time in range. Probably not even monitored as much as any member of this forum.


Then this study: Are the novel anticoagulants better than warfarin for patients with atrial fibrillation?

also paints a picture that the key problem is "patients can't be trusted" (conjecture: perhaps actually clinics blaming patients?)

Until 2009, warfarin and other vitamin K antagonists were the only class of oral anticoagulants available. Although these drugs are highly effective in the prevention of thromboembolism, their use is limited by the need for regular monitoring and the possibility of food and drug interactions. These limitations result in poor patient compliance and likely contribute to the underuse of vitamin K antagonists for stroke prevention

I'm not sure how those limitations resulted in poor patient compliance ... perhaps it was more the "measure INR every 6 weeks to 2 months" intervals of monitoring?


Essentially to me this is a "solution" without a problem.

 

[jlcsn2015]

Looks very complete information for 2012, we shall see what the new study shows,

Change is always present, like in the book "Who Ate My Cheese" ,

Aand if 10 year from now something is better than Warfarin,
i go for it, sure, why not/?,

things are always changing,

 

[Protimenow]

I don't think that I would go for 'something better than warfarin' unless it cost the same as warfarin. These new drugs - and any future drug - will be extremely expensive, and the patent will live on for years.

I'll continue taking my dime a dose warfarin, testing weekly, and. If I'm even still here in ten years, be happy to stay on warfarin.

 

[pellicle]

things are always changing,

true ... but with research dollars being what they are (and I'm still betting they haven't recouped the costs on the last "wonderDrug") I won't hold my breath.

As it stands however these are NOT new drugs and all that is happening is an attempt to allow them to be scheduled by the FDA as "suitable to Mech Valves" (which currently they are not).

Given that mech valvers represent perhaps 5% of the OA market its clearly just On-X looking for another marketing angle.

BTW, have you priced these drugs?

 

[dick0236]

[QUOTE="pellicle, post: 898149, member: 12469

Personally I like the devil I know

[/QUOTE]

I could not agree more! It is pretty safe for me to say that since I am one of the longest patients ever to take warfarin. I have also had a stroke while on warfarin(Coumadin) in 1974......and absolutely no problems since. That stroke was due to my ignorance of warfarin as well as the ignorance of the medical community that was managing my ACT. Today, that ignorance, generally, no longer exists among educated patients (not sure about many docs). If you are young, under 60, and have the sense to follow simple instructions........and want to minimize your risk of further surgical intervention.......take that little pill. If you are older it's a toss-up......just pray you don't need a followup surgical intervention in your 80's.

 

[jlcsn2015]

true ... but with research dollars being what they are (and I'm still betting they haven't recouped the costs on the last "wonderDrug") I won't hold my

Maybe yes maybe no, one thing is for sure, nothing is for ever true, and everything changes
and every body has different point of reference and personal opinions,
There are no absolutes,
I use warfarin and is ok , for me better than tissue, "for me "
Something better comes along, sure, i take it,
Of course, you can always stick to what you know, that is normal human experience,
Every body has his own perspective, the best about this forum, is that there are no rights and wrongs,
Not even the Cardiologists can choose a 1 solution fits all, part of life, is a dynamic system of multivariable connotations
changing over time as any differential equation...

 

[Protimenow]

If something better comes along, I'm not sure that I'd take it.

By something better, you probably meant an anticoagulant that doesn't require weekly testing. If, for example, one of the other anticoagulants (Eliquis, perhaps, or one of the others) gets FDA approval, my choice would be $16 a day (if I'm correct, it's about $8 a pill and I think you need two pills a day) versus warfarin (maybe five or six dollars a month - usually less if you don't need a few pills to make up your daily dose), and a weekly self-test.

For me, it would be no contest -- I'll stick with Warfarin.

Of course, the manufacturer of the alternate drug will do its best to make warfarin appear to be a harmful, dangerous drug. They'll probably circulate the stuff about warfarin being 'Rat Poison.' They'll send their detail people with pens, wall clocks, and other tchahtchkes selling the doctors on the perils of warfarin, and probably have special dinners and other events with some paid speaker talking about demon warfarin after feeding the doctors a $50 dinner. They may even compensate them for their time.

Unless the FDA pulls warfarin - and there's no reason that I can imagine for doing this (other than some gifts to a regulator), I'll stick with warfarin -- unless I'm dead first.

 

[pellicle]

Maybe yes maybe no, one thing is for sure, nothing is for ever true, and everything changes
and every body has different point of reference and personal opinions,
There are no absolutes,

agreed

but some things remain true for such significant amounts of time as to be within our life times unchanging, such as:

• the biggest influence on human health has been clean water and sanitation
• there are still only a few essential medications upon which humanity relies and these are usually the cheapest
• the most expensive changes usually effect the smallest groups
• like it or not we're one of the smallest groups

everyone can have an opinion ... but sometimes facts and scientific evidence are useful things

 

[Protimenow]

The auras that many of us get are 'orphan' symptoms -- not lucrative enough for any pharmaceutical company to work on a 'cure.' It's likely that the cure will be worse than the problem.

 

[jlcsn2015]

ASA Question: I have been using 81mg ASA + Warfarin as per On-X recommendations for my AVR, normaly my INR is some where in the 2 - 2.8 Range, On-X 1.5 -2 is said to be safe, but i have always aimed at 2+.

Currently 67, and it seems the "Long-Term" ASPIRIN intake needs to be stopped due to kidneys concern.

Would like to hear your comments about NOT using the ASA, and what levels of INR would be safe in order to avoid issues,

I dont think people with St Jude AVR are taking aspirin, but dont know if ASA is a general add-on that all people with mech valves take

Looking forward to hear from you,

 

[Protimenow]

I wouldn't worry about low dosage aspirin, unless you ALREADY have kidney issues. Many of us, myself included, have been taking one tablet daily with no negative effects.

I have a St. Jude mechanical valve, but stopped it for a while because I'll be taking Plavix for another ten months or so. Once I'm off Plavix (if I live that long), I'll go back to my daily low dose aspirin.

Also -- there's no advantage, and probable risk, to keeping your INR above 2 (as you're doing). On-X seems to have been using the 'lower INR' argument as a reason not to use any other prosthetic valve -- but there's really no difference to activities, quality of life, or other issues whether you keep your INR between 1.5 and 2 (not advisable) or between 2 and 3.5 or so.