PROSE trial results show ON-X and St Jude Equal performance

[tommyboy14]

Hi Team,

The PROSE trial, a randomised control trial between ON-X and St Jude valves, have now published their results.

https://www.sciencedirect.com/science/article/pii/S2666273622003084
From the abstract:
The total patient population (N = 855) included patients receiving an On-X valve (n = 462) and a St Jude Medical valve (n = 393). The overall freedom evaluation showed no differences at 5 years between the prostheses for thromboembolism or for valve thrombosis. There were also no differences in mortality.

From the text, they find lower rates of complications for both valves than previous studies:

The major late hemorrhagic rate for the On-X prosthesis was 1.0% per patient-year (n = 23) and for the St Jude Medical prosthesis was 1.2% per patient-year (n = 23). The major hemorrhagic rates were not differentiated by prostheses overall, by aortic and mitral valve positions, or by economic development. The TE event rates were undifferentiated for the On-X prosthesis at 0.5% per patient-year (n = 12) and for the St Jude Medical prosthesis at 0.5% per patient-year (n = 10)

The most prominent major complication was VT (10 events in 9 patients). Within the total population, the On-X prosthesis major complication rate was 0.2% per patient-year (n = 5) and St Jude Medical prosthesis major complication rate was 0.3% per patient-year (n = 5). The aortic valve position major complication rate was 0.1% per patient-year (n = 2) and the mitral valve position major complication rate was 0.5% per patient-year (n = 8) (P = .007). The thrombosis rate was differentiated by economic development: 0.04% per patient-year (n = 1) for the Western population versus 0.5% per patient-year (n = 9) in the Developing country population (P = .005). Review of anticoagulant therapy records in all VT patients showed that the INR status varied extensively or was not followed. The time postoperation from the original surgery was mostly relatively early (<1 year) but varied up to 4 years. One of the On-X prosthesis aortic position cases was not receiving anticoagulation therapy at all.

 

[Chuck C]

Thanks for sharing.

Good news that: "From the text, they find lower rates of complications for both valves than previous studies"

Important to also note:

"The target anticoagulation level for both prostheses was: for aortic position prostheses international normalized ratio (INR) between 2.2 and 2.8, and for mitral position prostheses INR between 2.5 and 3.5. "

"The PROSE trial revealed essentially equal performance for the On-X and St Jude Medical prostheses regarding influence of prosthesis type on major TE, VT, and major hemorrhage, as well as all-cause, valve-related, or unexpected mortality, when managed at target INR levels in the protocol representing standard of care"

I also found very interesting, the very low rate of Thrombosis and VT in the Western populations:

"The thrombosis rate was differentiated by economic development: 0.04% per patient-year (n = 1) for the Western population versus 0.5% per patient-year (n = 9) in the Developing country population (P = .005)"

"The rate of aortic VT by economic development was 0.05% per patient-year for the Western population (n = 1) and 0.2% per patient-year for the Developing country population (n = 1) (P = .340)"

The number of events was very low and many of the events which did occur appear to be attributed to non-compliance:

"Review of anticoagulant therapy records in all VT patients showed that the INR status varied extensively or was not followed. The time postoperation from the original surgery was mostly relatively early (<1 year) but varied up to 4 years. One of the On-X prosthesis aortic position cases was not receiving anticoagulation therapy at all."

Also, compliance appears to have been an issue in Developoing populations, particularly among young patients:

"The mitral thrombosis in the Developing populations occurred in a younger population, identified on multiple logistic regression, possibly due to anticoagulation compliance status because widely variable"

 

[Chuck C]

For folks on the On-x, if discussing with your cardiologist whether to consider using a lower INR of 1.5 to 2.0, one thing you might want to bring up for discussion is the significantly higher number of TE and VT events which occured in the PROACT Trial with the lower INR target, as compared to this trial, with a slightly higher INR target. PROACT used an INR target of 1.5 to 2.0 PROSE Trial INR target was 2.2 to 2.8 INR aortic and 2.5 to 3.5 mitral.

For The PROSE, the overall TE and VT- see the center figure in the chart below, were TE: 0.5% events/patient year and VT 0.2% events patient year. If you look below at the events per year of On-x, it mirrors this number with event rate of TE 0.5% and VT of 0.2% for a total of 0.7% events/patient year. Remember this is with the higher INR target used in PROSE.

Compare that to the PROACT Trial, which used the lower INR target of 1.5 to 2.0 for the On-x valve, with a TE and Thrombosis event rate of 2.96% events/patient year. See link below. In other words, the number of TE and VT events was more than 4x as high with the lower INR range, when the two trials are compared.

PROACT Trial:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472691/

 

[tommyboy14]

Fully agree that care is required with the On-X lower anticoagulation regime. If you look at the 'low-risk' patients in the PROACT trial, nobody appears to have had a stroke on standard warfarin therapy (exhibit B). Obviously, there is less observations as you go out, and I would say that the quality of the PROSE study is much better than the PROACT trial given sample size, different hospitals etc. Nevertheless, from a stroke perspective, PROACT supports PROSE. I.e. best way to avoid stroke is to stick to the current guidelines of 2-3.

 

[Timmay]

Given the On-X that is in me, this study makes me happy.

That said - I think it’s a great study in favor of the St. Jude valve. Why? The St. Jude has been around longer, with more data, AND it is significantly smaller in size. Bigger valve onto the same area without having to do an aortic root expansion like they did in me.

 

[Chuck C]

That said - I think it’s a great study in favor of the St. Jude valve. Why? The St. Jude has been around longer, with more data, AND it is significantly smaller in size. Bigger valve onto the same area without having to do an aortic root expansion like they did in me.

The main take away for me was how well both valves did- fewer events than previous studies. The number of bleeds and thrombotic events was very low, and the events that did happen appear to be largely attributed to poor warfarin managment, in some cases complete non-compliance.

For the patient that self tests and pays reasonably close attention to their INR and uses the ideal INR range to minimize events, I would expect even fewer events than observed in this study.

 

[pellicle]

View attachment 888859

and that's really interesting about that is that western has lower VT as I seem to recall that a member (from IIRC Malaysia) that I've chatted with here had classified westerners being "clotters" and asians as being "bleeders"
he wrote

According to my surgeon, Asians are "bleeders" & Caucasians are "clotters"

to me in a personal communication

 

[Superman]

The main take away for me was how well both valves did- fewer events than previous studies. The number of bleeds and thrombotic events was very low, and the events that did happen appear to be largely attributed to poor warfarin managment, in some cases complete non-compliance.

For the patient that self tests and pays reasonably close attention to their INR and uses the ideal INR range to minimize events, I would expect even fewer events than observed in this study.

If I had to guess, I’d say the more recent the study, the more likely participants were home monitoring their INR and therefore more compliant. Greater compliance equals fewer events.

 

[pellicle]

Fully agree that care is required with the On-X lower anticoagulation regime. If you look at the 'low-risk' patients in the PROACT trial, nobody appears to have had a stroke on standard warfarin therapy (exhibit B).

I've made the observation before that the duration of the PROACT trial is interestingly designed that the length of that expected incidents (26/100 years makes it likely that an event will occur in 3.8 years (statistically).

so all you've got to do is move some of those "higher risk" patients or double down on the INR testing to be higher frequency when INR is low and it all looks good.

but its all good

 

[dornole]

I thought it was interesting about the younger mitral patients in “developing” vs “western” countries. I think rheumatic mitral valve disease (like I have) is much more common in India and hits people who are quite young (like in your 20s young, not “valve patient” young like 60). At least this is what I was told by docs and residents coming to check out my rheumatic murmur because they had never heard one. It doesn’t surprise me that young adults might be inconsistent with managing inr.

 

[Timmay]

The main take away for me was how well both valves did- fewer events than previous studies. The number of bleeds and thrombotic events was very low, and the events that did happen appear to be largely attributed to poor warfarin managment, in some cases complete non-compliance.

For the patient that self tests and pays reasonably close attention to their INR and uses the ideal INR range to minimize events, I would expect even fewer events than observed in this study.

For sure Chuck. I am just doing a personal, opinionated extrapolated conclusion (yes, I just made up that fancy phrase, lol).

I just don't see the reason to stab a bulky mech valve into a place where a more sleek and streamlined valve can get the same work done in the same manner with the same results.

 

[Chuck C]

For sure Chuck. I am just doing a personal, opinionated extrapolated conclusion (yes, I just made up that fancy phrase, lol).

I just don't see the reason to stab a bulky mech valve into a place where a more sleek and streamlined valve can get the same work done in the same manner with the same results.

It is an interesting point you made that this study is a win for St. Jude over On-x. As you note, St. Jude has a much longer track record. The big marketing angle for On-x has been basically that they overcome this objection because they have a special treatment, which they argue will make the surface area of their valve less prone to thrombotic events. The fact that they had no statistical advantage over St. Jude in this study means that they do not appear to have this anti-thrombotic advantage over St. Jude, and this marketing angle gets muted, at least as suggested by the outcomes in this study. So, yes, this would be a win for St Jude. Having said that, both valves did very well with a low number of events, both thrombotic and bleeding. In my view, they are both good valves.

 

[tommyboy14]

Another interesting way to look at the event rate of 0.5% of thromboembolic event per year and compare it to the incidence of stroke in the General population.

The paper below suggests that the life-time incidence of stroke in someone aged 50 is roughly 20% in the general population.
https://pubmed.ncbi.nlm.nih.gov/32090315/
In the PROSE study, the average age of patients was round 52.3. So the lifetime incidence of thromboembolic event by the time this person is 92.3 is 20%.

I do wonder why Cardiologists/Doctors in general do not compare these numbers to the incidence of stroke in the general popuation. I also wonder why all of the previous mech valve studies dont make this comparison. Even if you considered that the thromboembolism rate is higher than 0.5%, I personally find the comparison to the general population useful: It suggests that some of these adverse events are more about patients than valve, so long you keep your INR in your prescribed range. Indeed, the authors of study argue that adverse events occurred when anti-coagulation was poor...

 

[pellicle]

Good Morning @tommyboy14

great posts and just reading the latest one. I recall reading that well managed INR (no not usual care of a miserable 70% in range) gave aortic valve patients a risk of stroke or bleed of at least equal to the age corrected general population.

Sadly at this stage I was not a member of VR and was not reading like a researcher to answer other askers questions but just as a patient understanding my situation.

Once I started participating here I re-engaged my approach of a citations database to have a quickly searchable resource of my findings. This is something I learned and honed during the years I was researching writing my masters thesis.

 

[pellicle]

I do wonder why Cardiologists/Doctors in general do not compare these numbers to the incidence of stroke in the general popuation.

postulation:

• they don't understand statistics (research shows that medical science has among the flimsiest grasp of statistics
• generally speaking the population don't understand statistics (cites lotto and casions as evidence)
• generally speaking the population don't want to understand they just want the priest to cure them them so they can go back to ignoring their health again and taking everything for granted.

 

[Astro]

That is great that both St Jude and ON-X are equally good. No need to worry about what brand was placed in your chest or what brand will be placed in your chest. (Though, might upset some advertisers)

 

[pellicle]

Though, might upset some advertisers

we haven't been an On-X site for a while now ;-)