St Jude Valves

[pellicle]

In the US, generic drugs need to be approved by the FDA. https://www.fda.gov/media/89135/download

a very interesting summary, thanks for posting it. I do wonder however if that process may not have shortcomings with respect to warfarin where the different enantiomers (stereochemistry forms similar to your left hand and your right hand being mirror images but well made gloves won't fit on either hand unlike disposable latex ones) are known to have different metabolisms
https://www.ncbi.nlm.nih.gov/pubmed/9014207

Abstract
The anticoagulant drug warfarin occurs as a pair of enantiomers that are differentially metabolized by human cytochromes P450 (CYP). R-warfarin is metabolized primarily by CYP1A2 to 6- and 8-hydroxywarfarin, by CYP3A4 to 10-hydroxywarfarin, and by carbonyl reductases to diastereoisomeric alcohols. S-warfarin is metabolized primarily by CYP2C9 to 7-hydroxywarfarin. ... The efficacy of warfarin is affected primarily when metabolism of S-warfarin is altered.

that its noted that brand substitution causes INR changes I suspect that such approval process does not cover this adequately.
For instance:
https://www.ncbi.nlm.nih.gov/pubmed/21449627

...In one observational study, however, a change in therapeutic INR control after the switch to generic warfarin was reported at the individual patient level. The results of our systematic review suggest that generic warfarin products may be as safe and effective as brand name products and that patients may be safely treated with these products. However, closer monitoring may be reasonable when switching brands, as variations in individual INR response may be seen.

 

[tom in MO]

Per your first citation, the literature on warfarin is vast and old (i.e. pre-internet). A study of the stereochemistry of a drug is usually done in the experimental work and clinical trials and documented in the final approved New Drug Application. This document is updated every year by every US manufacturer of warfarin, and if adverse events are linked to the stereochemistry, it should become evident over time. If the stereochemistry is found to be significant, the Active Pharmaceutical Ingredient and Drug Product have controls put on it, in the form of specifications for the relative amounts of each stereoisomer. For some materials only one isomer is biologically active. There are some drugs, where in one dosage form the stereochemistry was important but in another it was not, due to the body's metabolic pathways (i.e. skin absorption vs. ingestion). Given the powerful effects of warfarin's active ingredient and the huge number of people who have taken warfarin for many years, I personally would feel it safe to assume the stereochemistry of the active ingredient has been worked out. The USP tests for warfarin Active Pharmaceutical Ingredient and Finished Drug Product do not include tests for the stereochemistry.

Per your second quote on the observational study, what I find more compelling is this quote from the same paper's abstract"

"In three crossover trials evaluating the mean difference of the international normalized ratio (INR) after switching to the alternate formulation of warfarin, no statistically significant difference was found between patients randomly assigned to receive brand name or generic warfarin. The two other randomized trials found no significant differences in the magnitude or number of dosage changes between patients switched to brand name or generic warfarin." ​

​

In general, randomized studies are considered the gold standard in comparison to observational studies. There were 11 studies examined in this paper and only one, an observational study, showed an effect, thus the overall conclusion "The results of our systematic review suggest that generic warfarin products may be as safe and effective as brand name products and that patients may be safely treated with these products."

There was a time when there were differences between generic and brand name drugs sold in the US. This was due to poor regulations, lax enforcement and also bribery, fraud and collusion between the USFDA and the executives of Par Pharmecueticals. FDA officials were bribed to turn their heads when studies to support the generic drug actually compared the brand name product to the brand name product, not the generic. This fraud and collusion was discovered and resulted in the Generic Drug Enforcement Act of 1992. In the 21st century, the USFDA is pretty strict when it comes to generic drugs. However, this is an international forum, what is true for US drugs is not always true in other places.

 

[Protimenow]

These studies may use small samples. They may not study ALL available generics. The conclusion may not apply to ALL available generics, or any drugs made available after the study was published, or to changes made to the drugs that were included in the study.

I have only anecdotal evidence that, for me, another 'generic' warfarin - with a different brand name - made it difficult (if at all possible) to regulate INR. I told the pharmacy that I was unable tocontrol my INR with this particular medication, and they returned to my former generic.

If the pharmacy ever switches me to a generic from a different manufacturer, I always check after a few days to make sure that the results of this new generic remain the same as they were with the other. If not, I'll test every few days, perhaps adjust dosage and try to bring INR into range, and, if unsuccessful, switch back to a generic that I know I can use to control my INR.

 

[Agian]

'Stereochemistry' sounds like a Prince song.

 

[carolinemc]

I have no issues with my St. Judes' valve. Feel better and doing great at 18 years post op. Just hate it when INR drops too low or goes a little high.

 

[MMReese]

Two St. Jude mechanical valves since 2008. No issues.

I currently have a Bjork Shiley mechanical aortic for 37 years. Now I need a Mitral replaced. How is the clicking with 2 valves?

 

[pellicle]

Thanks for your long answer however...

..., I personally would feel it safe to assume the stereochemistry of the active ingredient has been worked out.

agreed, its well documented in MIMS and is what I said it is: The R enantiomer has longer half life (about double) and the S is more active.

I would be very interested to see any evidence that the drug companies are required to put exact amount of the enantiomers in a drug, to my reading it only discusses biological availability, which in this case is high in both.

 

[vitdoc]

I have written about what I have seen with the On-x valve and the lower INR requirements. The data was not compelling. I am sure the valve is fine but the lower INR requirements may not be truly accurate. If I were getting a valve today I might consider the On-x but it clearly doesn't have the tract record of the St. Jude. So I would think long and hard about it. I had my first St. Jude in 1983 age 35 . It was removed and replaced with a new St. Jude and aorta in 2006. So far no issues.

 

[Chris]

My St. Jude is almost three months old (!). No issues so far.

 

[Protimenow]

There shouldn't be issues for decades - or longer.

Just be sure to get a meter and keep an eye on your INR.

 

[Keithl]

I have written about what I have seen with the On-x valve and the lower INR requirements. The data was not compelling. I am sure the valve is fine but the lower INR requirements may not be truly accurate. If I were getting a valve today I might consider the On-x but it clearly doesn't have the tract record of the St. Jude. So I would think long and hard about it. I had my first St. Jude in 1983 age 35 . It was removed and replaced with a new St. Jude and aorta in 2006. So far no issues.

I think the only concern with On-X is the bogus lower INR need. I know saying bogus is hard, but the small sampling to get that approved I did not trust and stay 2-3 with the target being around 2.6. I also do daily 81mg aspirin. I have been mostly between 2.6-3.0 with a small dip to 2.3 for a week which was no big deal.

 

[Protimenow]

It sounds a bit bogus to me. I hope that it's not dangerous to those who maintain their INRs around 1.8 - because this probably puts their INRs in a range from about 1.5 - 2.1 or so. A particular meter would report 1.8, but the labs may report 1.6. To me, this is cutting it pretty damned close.

An On-X patient would probably still need Warfarin to get to the sub-2.0 level. It's not really a problem for the millions of people who maintain their INRs in roughly 2.5 -3.5 range, so I find it rather difficult to find a good sales point for that small questionable reduction in required INR.

If people weren't sold so many myths and lies about how terrible it is to be on 'blood thinners', the need for slightly less wouldn't be much of an advantage over St. Jude and other prosthetic valves.

 

[DDT77]

I have an On-x, so target INR range 2.0-3.0. I think I can tell when my INR is on low side ~ 2.0, due to increased visual aura. Does anyone else perceive a similar phenomena?

 

[Protimenow]

I have an On-x, so target INR range 2.0-3.0. I think I can tell when my INR is on low side ~ 2.0, due to increased visual aura. Does anyone else perceive a similar phenomena?

It's interesting that you would ask this.

I got my AVR 28 years ago, long before meters for self-testing became available and affordable. I wasn't very good about going to the lab to get a blood draw. I didn't know then how important it is to stay in range and test regularly.

Like you, I thought that I could tell, from certain physical signs, whether my INR was too low or too high. I'm not sure, now, what those 'signs' were, but it may have been an increase in the number of auras when my INR got low. I don't remember specifically what it was that made me sense that my INR was too low. I wrote about it on a different forum, and was kicked out because I talked about it.

So -- even though you may be able to sense when your INR drops, don't rely on that.

Meters are accessible and affordable. Strips are not especially expensive. Meters may be more accurate than labs.

I URGE you to test weekly - either self-test or do the testing at a clinic - but TEST REGULARLY.

If you like, you can still correlate the frequency of your auras with your INR - but you'll have a number that you can accurately connect the auras to - rather than guessing.

 

[tom in MO]

I have written about what I have seen with the On-x valve and the lower INR requirements. The data was not compelling. I am sure the valve is fine but the lower INR requirements may not be truly accurate. If I were getting a valve today I might consider the On-x but it clearly doesn't have the tract record of the St. Jude. So I would think long and hard about it. I had my first St. Jude in 1983 age 35 . It was removed and replaced with a new St. Jude and aorta in 2006. So far no issues.

Seven years ago when I was deciding on valve type, there was a lot of buzz on this forum for the On-x. The hope was for the lower INR range, which has since been approved. I asked my surgeon and he said he puts in St. Jude valves, but if I wanted an On-x that he'd put that in, he'd just have to order one. I asked him why St. Judes over other valves. He said "track record." That's all I needed to know. The INR range for the St. Jude (aortic position) was tightened about 8 years ago from 2-3 to 2-2.5.

I needed an operation, TAVR, a year ago and needed to drop my INR to 1.5 or less. I could do it w/o bridging. I asked my cardio "Why no bridging?" since I had read about that on this forum. He said the St. Jude valve was well characterized and the risk associated with dropping my INR for a short time was minimal. He was right. When my INR went a little wacko and I dropped to 1.5, my coumadin clinic told me the same thing. They upped my warfarin dose and did not require any other type of anticoagulation therapy.

 

[Protimenow]

Tom: I've had the same experience.I had a sinus surgery a year or two ago, had to drop INR to 1.5. I didn't worry about Lovenox - I knew that on my regular dose, within 3 days, my INR would be back to normal.

A day or two (or three) below 2.0 doesn't seem to be a problem.

According to research by Duke University Clinic, it takes about a week below range for a clot to form and detach.

 

[ForeverThankful]

Tom and Protimenow.... Same here, my cardiologist told me to just drop my INR to 1.5 for procedures. No bridging.

My surgeon said that he only uses St Jude valves because of their track record. I'm quite happy with my St Jude.

 

[Protimenow]

When it's your life (or a patient's life) on the line, it's kind of hard to justify going with something new (and potentially unproven) than it is to go with a product with a 30+ year positive track record. It's probably even harder to justify taking the risk of dropping your INR below 2.0, when it's no big deal to have an INR slightly higher. You're really not gaining anything by not having to keep a manageable, safe INR that millions (?) of people with mechanical valves are doing.

 

[Keithl]

When it's your life (or a patient's life) on the line, it's kind of hard to justify going with something new (and potentially unproven) than it is to go with a product with a 30+ year positive track record. It's probably even harder to justify taking the risk of dropping your INR below 2.0, when it's no big deal to have an INR slightly higher. You're really not gaining anything by not having to keep a manageable, safe INR that millions (?) of people with mechanical valves are doing.

I agree. When I had to make my decisions I went with my research and gut. While On-X is newer I felt the valve itself is proven, but not the lower INR part. Mechanical valves have an excellent track record with well managed INR. The bleed risk of running INR in the mid 2’s is low vs. the risk of lower INR or a dangerously low swing.

 

[user 15848]

The people that created On-X worked initially at St Jude, so they carry its experience, also, the On-X has 1 "one" design difference from all the others that makes a difference, and that is the "90 Degrees Angle" of the opening; i was told about that point by 3 OHS Surgeons in different countries, and for them, that 1 difference is an improvement over all the others;