Clinical Trial Update: PROACT Xa Evaluates a Mechanical Valve Replacement Without Warfarin

For the past 50+ years, patients with mechanical heart valve replacements have been required to take warfarin to prevent the possibility of blood clots forming on the valve.  At times, this requirement has caused agony for patients during their valve selection process. Many patients want the durability of a mechanical valve.  But, they don’t want to take warfarin.

It’s for this reason that many patients and surgeons are excited about the new PROACT Xa clinical trial. In this special research study, the On-X mechanical heart valve replacement will be evaluated for safety-and-efficacy without the use of warfarin in the aortic position.

To educate our community about this very unique clinical trial, I just interviewed Dr. Marc Gerdisch, the Chief of Cardiac Surgery at Franciscan Health in Indianapolis, Indiana, who is already a leading enroller in this study.

Key PROACT Xa Learnings from Dr. Gerdisch

Dr. Gerdisch, who has over 100 patient testimonials in our community, shared several important points during this interview:

• Patients require a heart valve replacement procedure if their defective valve cannot be repaired (restored to proper function).
• There are three categories of heart valve replacements available to patients including mechanical heart valves, tissue valves (pig or cow), and transcatheter heart valves (e.g. transcatheter aortic valve replacement).
• Each valve type has its advantages and disadvantages.  Mechanical valves are very durable but require patients to take warfarin.  Tissue valves typically last between 10-15 years and many patients are not required to use any form of medicine post-operatively.  Transcatheter valves are tissue valves that do not require an incision to the patient’s chest or ribs. However, this new technology is evolving and long-term durability for these valves is not known at this time.
• Patients with mechanical valve replacements are required to be on warfarin, a blood thinner, also known as Coumadin.  Patients must be monitored with lab or remote testing to ensure their INR is at an appropriate level to not cause any risks for the patient (e.g. stroke, bleeding).  Patients on warfarin should not eat certain foods and should not drink alcohol heavily.

On-X Mechanical Heart Valve Replacement

• The PROACT Xa clinical trial represents a 20+ year journey of research and development specific to the creation of a mechanical valve that does not require patients to take warfarin.  In this research study, the On-X mechanical valve is being evaluated for safety-and-effectiveness without the patient use of warfarin.
• The PROACT trial, conducted several years ago, was the precursor of the new PROACT “Xa” trial.  The earlier PROACT trial resulted in an FDA approval for lower warfarin usage with patients with the On-X mechanical valve in the aortic position.
• The On-X mechanical valve is made from a pure form of pyrolytic carbon, a unique substance that was developed by Dr. Jack Bokros. Under an electron microscope, On-X pyrolytic carbon looks like “a sheet of glass”, “mimics a normal aortic valve”, and “has a normal flow pattern into the aorta”, according to Dr. Gerdisch.
• Instead of warfarin, patients are required to use a blood thinner, Eliquis, during the PROACT Xa clinical trial.  Eliquis (or apixaban) will be used in the PROACT Xa study to protect patients from potential blood clots and bleeding risks.   Unlike warfarin, Eliquis will not require patient to check their INR levels.  The dosage will be one pill, twice a day.
• While there is much to learn during this research study, the patient response to the PROACT Xa trial has been very favorable.
• To be considered a candidate for the PROACT Xa clinical trial, patients must have had the On-X mechanical valve implanted for at least three months.  Then, three months after implantation, patients who enroll in the study will be randomized in the clinical trial.
• Dr. Gerdisch’s key pieces of advice for patients needing heart valve replacement surgery is (i) to research their options as there are subtle differences for each valve type that patients should consider before their operation and (ii) as patients prepare for their “golden moment” of surgery, patients should ensure that their medical team is addressing all of their cardiac issues which may include atrial fibrillation, changes in their aorta and other valvular defects.

Thanks Dr. Gerdisch and Cryolife!

On behalf of our patient community, I want to thank Dr. Gerdisch for taking the time to share his clinical experiences and research specific to the PROACT Xa study and the On-X mechanical heart valve replacement.

Dr. Marc Gerdisch – Top Enroller in PROACT Clinical Trial

I also want to thank Cryolife, the sponsor of the PROACT Xa research study and the manufacturer of the On-X mechanical valve replacement, for this extraordinary effort to realize the possibility of a mechanical valve replacement that does not require the use of warfarin.

Related Links:

• Dr. Marc Gerdisch Celebrated With 115 Patient Testimonials!
• About the On-X Mechanical Heart Valve Replacement
• Rapid Recovery Protocol: 5 Facts to Know

Stay tuned!  I will be sure to update our community as we learn the results of this clinical trial.

Keep on tickin!
Adam

P.S. For the hearing impaired members of our community, I have provided a written transcript below.

Adam Pick: Hi, everybody, it’s Adam with HeartValveSurgery.com, and today we have a very exciting surgeon question-and-answer session all about the new PROACT Xa clinical trial. To answer your questions, we’re going to bring in Dr. Marc Gerdisch, who is the Chief of Cardiac Surgery at Franciscan Health in Indianapolis, Indiana. Dr. Gerdisch, are you there?

Dr. Marc Gerdisch: I’m here. Hi, Adam, thank you.

Adam Pick: Dr. Gerdisch, I can’t thank you enough and if there’s one thing I want to share with our community, everybody watching now, is that Dr. Gerdisch is celebrated by the patients and the caregivers at HeartValveSurgery.com. He’s educated folks, he’s empowered folks, and he’s also performed successful heart valve surgery on folks like Angie Gregory, Todd Runenbaum, Linda Staples, Linda Kincaid, and he has over a hundred patient testimonials at our website. Dr. Gerdisch, I can’t thank you enough for being with us today.

Dr. Marc Gerdisch: Thank you, Adam, and it’s nice to be part of the family. It’s unbelievable how so many people are so involved, and I love that people communicate through your site.

Adam Pick: Can we maybe start off with a little bit about you? What was it about heart valve therapy, repairs, and replacements that made you make such an important part of your cardiac practice?

Dr. Marc Gerdisch: It’s a difficult question to answer because it happened over the course of my career. I think I often feel like heart valve surgery chose me as much as I chose it. As a teenager even, I was – I had a very romantic notion about cardiac physiology and as I learned more about structure and physics of the heart, I became very enamored with the function of the valves, the integral performance of the valves in the heart and how the synergy existed between heart valves and the heart itself, such an elegant relationship. I wanted to participate in restoring it to function when I could.

Adam Pick: Got it, and restoring that function for your patients, you definitely have – I’ve heard all about the research. I’ve seen the research you do, the innovations with the rigid sternal fixation, cryoanalgesia, and I understand that minimally invasive therapies has been a big part of your practice. Can you talk about how that is impacting the patients who are coming to you for heart valve surgery?

Dr. Marc Gerdisch: That’s truly very important for so many of my patients that want to get right back to full activity. I think that the most important thing in any operation is a perfect operation on the valve [itself, repairing the valve, restoring it to normal function, making sure the heart is well. The next thing that’s really important to people is how quickly they get back to their normal activity. What level of change in their chest architecture has there been? How comfortable are they? For so many of our patients, we’ve been able to move over to very small incisions, very minimal discomfort, and get them back into full action quickly.

Adam Pick: Dr. Gerdisch, I want to ask you to help the patients contextualize the difference between a sternotomy and a minimally invasive approach. Can you maybe talk about that and maybe use your hands to show the different access points you use?

Dr. Marc Gerdisch: Sure, it’s my pleasure. I do think it’s important for patients to genuinely understand it. Sternotomy is any time that we divide any part of the sternum. There are operations that we’ll do through mini-sternotomies, and we still consider that a minimally invasive operation, but we’re dividing bone, and that is different than not dividing bone, so going through the sternum. When we do have to go through the sternum, in our practice we always use rigid sternal fixation when we finish. In other words, we do an orthopedic repair of that bone to return it to full function immediately after surgery

In general, though, we stay off of the sternum. The vast majority of the operations we do through a small incision on the side of the chest, so for an aortic surgery, we do it through an incision right here, a small incision right here next to the sternum. For mitral surgery, go through a small incision right underneath the right nipple. Either way, not a very big incision, which is nice cosmetically More importantly, no cutting of bone, no breaking of bone, no dividing anything except separating the muscle fibers and putting them back together. That, along with relatively advanced methodologies for localized analgesia have provided us with super fast recovery and a comfortable patient.

Adam Pick: A question that many newly diagnosed patients is why do I need a heart valve replacement?

Dr. Marc Gerdisch: Sure, so I think to start off with, a heart valve has to be replaced when it can’t be repaired. We always will look at a valve first for the opportunity to repair it, whether it’s a mitral or aortic valve. If it cannot be repaired, if it cannot be restored to function, the patient’s always better off with their own tissue. It is the primary reason people do so well for so long with their own heart valves, right? When we have to replace it, we want to use the appropriate device for that patient and if possible, we want to implant it through the least traumatic and the smallest access. The vast majority, nearly all of isolated aortic valve replacements in my practice are done through a small incision usually without touching the sternum, so staying away from the bone and working between the ribs.

I feel like we’ve really mastered a technique for creating analgesia in that space that although it provides a little bit of numbness, and that can last for several weeks, it also provides a really comfortable recovery and that allows people to get right back in action doing whatever their normal activities are.

Adam Pick: Can you describe the different types of valve replacements that are available to patients?

Dr. Marc Gerdisch: Right, so now there are a lot of options. Over time, that’s expanded a little bit. I think that most people who are experiencing valve problems become familiar with really three general categories: mechanical valves, which sometimes people call metal valves although they’re actually made of carbon; bioprosthetic valves or biologic valves, which actually has two components One are the standard surgical biologic valves, which are made of cow tissue or pig tissue. Cow tissue valves are made from the sack around the heart of a cow. Pig tissue values are made from the leaflets of a pig valve. Then there’s a third category that’s a sub-category of that, which is the transcatheter valve. Those are really the three general categories that when we meet any given patient, we have a conversation about all of those possibilities

Adam Pick: Can you talk about maybe the advantages or maybe even disadvantages of the different valves you just mentioned?

Dr. Marc Gerdisch: The conversation is always the same only adjusted a little bit based on a person’s age and the things we call comorbidities, other issues that they have, the physiologic challenges or even physical challenges that they have. We try to frame it according to that. My conversation usually begins with really spending some time just understanding what the patient is looking for, what their expectations are, what their hopes are. It’s true that, for example, a mechanical valve may never need another operation, probably will never need another operation. They last the entirety of your life, but you do have to be on blood thinner. Tissue valves, you don’t have to be on blood thinner, but they do have a clock on them. As soon as they’re implanted, they start to change a little bit and over time, they’ll require a second or even a third operation depending on the age of the patient when they receive it.

The transcatheter valves were still an evolving technology with them. We love them because they provide rapid treatment for patients. The vast majority of our patients go home the next day after a transcatheter valve, but we’re just really learning about their durability. They have certain drawbacks with respect to the requirement for pacemakers and also the challenges of a second valve being needed or a third valve if they need it. those become more complicated for those patients.

Depending on a patients age, the demands of their lifestyle, their other medical issues – all of those factors get compiled into a thorough discussion of what the options are for the patient.

Adam Pick: Great, and let’s maybe focus in now on the mechanical valve set, which is often, as you referred to as the durability. A lot of the patients I speak with often say hey, I want a one-and-done. Then they talk about the use of blood thinners. Can you maybe talk and share with the patients what the expectations should be for a patient who goes on blood thinner. Is there anything they should know about being on a blood thinner for the rest of their life?

Dr. Marc Gerdisch: The thing about blood thinners with valves is that it’s the same as blood thinners with anything else. Patients have to be on blood thinners for clots in their veins, for clots that go to their lungs, for atrial fibrillation In fact, even in tissue valves, if you look at the literature, roughly about a third of all the patients that have tissue valves are also on blood thinners. Blood thinners, in and of themselves, present their own challenges. They’re a medication that have an indication for different disorders.

One of the conditions that a blood thinner is necessary for is when a patient has a mechanical valve. The real challenge with a blood thinner is that if the blood gets too thin, the patient can bleed. That’s the complication you run into with blood thinners. People are naturally very concerned about that, especially if they have active lifestyles. I can tell you that a lot of people that play basketball, go skiing, do all their normal things on blood thinners. The point is that if you’re going to be on a blood thinner, you have to have good control over it. In fact, when we have patients on blood thinners for mechanical valves and it’s warfarin or Coumadin, we have those patients almost invariably arrange to have home monitoring. We just check it once a week, and we make sure it’s in the zone and they go about their lives.

Still, though, for a mechanical valve, for all mechanical valves except for one, you have to be on a fairly high dose of the blood thinner. It puts you in a range that has some risk attached to it. Several years ago, we did a study called the PROACT trial, and we proved with randomized control studies, so the most rigorous type of science you can use – we proved that for a particular type of mechanical valve, the Onyx valve, that we could run that at a lower dose of blood thinner, that we could bring what we call the INR, which his what we measure to ascertain how thin the blood is – we could bring that down into a range never before used for mechanical valves, and it proved to be perfectly safe. There was no increase in the threat, which is thrombobolic events related to the valve, stokes, or clots. No increase in that, while decreasing the incidence of bleeding complications by 60%. Sixty percent sounds like a big number, but it’s actually a huge number because if you look at – if you compare that to the leading events for patients who have tissue valves – like I said, many of them have to be on blood thinners anyway – it’s about the same. We pretty much neutralized the impact of it.

Still, though, there’s inconvenience. You got to take your pill, got to check it. There are certain foods you can’t eat a lot of or you can’t binge on. You can’t drink heavily; you can’t binge drink. There are things like that, all of which are guidelines that we should follow for a healthy life anyway, but they pertain to people that are taking that medicine for their mechanical valves.

I think it’s important that people understand that when we put any kind of valve in a person – it doesn’t matter, any of those categories – that valve is not part of their normal body, right? The body identifies it, and the body reacts to it in some way. In the case of mechanical valves, it’s that they have a little bit higher – they have a higher tendency of getting a little bit of clot on them, right? That’s why you have to be on the blood thinner. The biologic valve, it’s that your body identifies it as foreign and your body attacks it and over time, the leaflets become calcified or they tear because they are deteriorating It’s a matter of choosing the process that suits you the best. Like you mentioned before, one-and-done, right? There are patients who say okay, well, I’ll just take that lower dose of blood thinner, I’ll have my monitor at home, and I’m finished. That’s all I’m going to do for the rest of my life. Other folks don’t want to do that. They don’t want to have to monitor. They don’t want to have to take pills or they don’t want to monitor it. They don’t want to deal with even a little bit of a bleeding risk, and so they’ll take a tissue valve with the understanding that if they’re younger, they’re going to need another procedure sometime in their life.

Adam Pick: We have heard today about the mechanical valves and how they’re used with patients. Then we learned all about the PROACT trial and the success that you had there with lower doses of blood thinners. Now we’re hearing about the PROACT Xa trial. Can you please share with all the patients out there what is so special about this clinical trial?

Dr. Marc Gerdisch: Sure, so Xa is Roman numeral 10a, and Xa is part of our coagulation cascade, so factor Xa is responsible for converting prothrombin into thrombin, so thrombin is something we all have in our blood that allows us to clot or promotes clotting. By inhibiting Xa, there are medications that inhibit Xa, they prevent or reduce clotting. I’m sure patients have seen advertisements on television for drugs that are used for clots to the lungs or atrial fibrillation, these newer drugs. This is one of those newer drugs.

The drug that we’re using in PROACT Xa is ELIQUIS or apixaban. It’s a Xa inhibitor. After rigorous review and a great deal of contemplation both on the part of the scientific committee and on the part of the FDA, we have started a trial called PROACT Xa which will, again, be a randomized study, meaning that we will compare patients who have the drug ELIQUIS versus patients who have the drug warfarin for an extended period of time to determine if they are equivalent Indeed if they are, then whoever would like to, if someone wants to switch from warfarin to ELIQUIS, they’ll be able to do that.

Someone might say why bother? The reason is that if we’re able to switch to ELIQUIS, it takes the inconvenience away. The inconvenience of warfarin is that you have to check in. The inconvenience of warfarin is that you do have to watch your diet a little bit. You have to pay attention to some things. With ELIQUIS, you just have to take the pill twice a day. Assuming that works out well, then we’re going to have a scenario where a patient can have the Onyx valve, the Onyx mechanical valve, and then be on ELIQUIS and ELIQUIS alone or with a low-dose aspirin, and not have to check their blood thinner levels and have the same type of protection and the same type of durability

I would add that it’s important for people to understand that there’s been a journey we’ve been on with this particular valve. In 2002, I met Jack Bokros. He’s the guy who invented the valve, but more importantly Jack Bokros invented pyrolytic carbon, and that is the material that every single mechanical has been made of for 20 years. Everybody who has a mechanical valve has their valve made of pyrolytic carbon. Dr. Bokros, though, had in his mind a goal to eventually be able to build a valve that was pure carbon. Pyrolytic carbon – they’re all pyrolytic carbon, but pyrolytic carbon originally required silicon to be doped into it so it could be dispensed onto the leaflets evenly. Finally he created one that was pure carbon, and that’s the Onyx valve. When we look at that valve under an electron microscope, it looks like a sheet of ice compared to all other valves, which look kind of like a gravel road. You can imagine the blood seeing that smooth surface is less likely to be promoted to foreign problems. Furthermore, the design of the valve is engineered so the flow through the valve mimics that of a normal aortic valve. This is extremely important for the type of flow not only through the valve but once the blood gets on the other side of the valve into the aorta that it has normal flow pattern.

We think all of that, along with washing jets to the valve, contributed to having it – contributed that valve to having a lower likelihood of developing clot. That’s why we were able to lower the dose of warfarin and that’s why now, we’ve been cleared to do the Xa study, which we’ve already started and actually, our center is the highest enroller in the nation for that already.

Adam Pick: I’ve got to ask you the question: when your patients – when you share the PROACT Xa clinical trial with the patients that have an Onyx valve, what’s the response? What are you hearing back from the patients?

Dr. Marc Gerdisch: If there’s the opportunity to move from something they have to check to something that they don’t have to check. There’s a real advantage there. Plus, we know that – from the studies, we know that ELIQUIS is a safe drug with respect to bleeding. If we look at all the studies comparing the newer anti-coagulants, ELIQUIS has always fared the best or at least as good as every other drug with respect to the risk of bleeding. In general, they’ve been very interested. Patients are asking to be evaluated and as we evaluate them, we’re enrolling them.

Adam Pick: Yeah, and that’s the next – the question. If you are a patient, how do you participate in a trial like this PROACT Xa?

Dr. Marc Gerdisch: So Xa is available to anyone who’s had an Onyx valve for three months, basically. When we initially implanted the valve – for example, let’s say I have a patient tomorrow for whom I implant an Onyx aortic valve. Then three months after the implantation, they would be eligible to be randomized. In other words, they’re either going to get ELIQUIS, or they’re going to get warfarin, and then they stay on those tracks until the study’s finished. It also then applies to anybody who had their valve put in last year or the year before as long as it’s been three months since the implant. First we’re starting with the most recent folks and we’re working our way back toward folks who have had their valve for quite a long time. I expect there’s going to be pretty robust enrollment.

Adam Pick: Yeah, I got to tell you, Dr. Gerdisch, my inbox has been lighting up with questions about this clinical trial, so it seems like the patients here are ready to try something new and different and get enrolled and see if they can’t help you and your team advance the valvular therapy specific to this Onyx valve. Got one more question for you before we wrap up is what else should patients know about the PROACT Xa trial from your perspective? What do you see is the future here for mechanical valves and patients as well?

Dr. Marc Gerdisch: I think that we’ve learned a lot in the last decade, really, as new technologies have come on the line. We’ve recognized that there are some high-value players. The Onyx value we knew was a high-value player when w were able to perform the original PROACT study, and there was a lot of energy and interest invested in that by a lot of major centers and really great surgeons. There were so many implants and so many patients on the lower dose warfarin regimen that it became obvious that the performance of the valve was different.

I think the most important thing in that sense is that first of all, there is a valve that you can be on a lower dose of blood thinner, which is amazing. The other thing is that there is a valve that potentially you could be off warfarin. I think those are the important messages for the PROACT Xa study. I think maybe more globally, though, I think as a patient looks at their options for valve surgery, they need to think about the type of valve. When they choose the type of valve, they should learn which specific valve they’re going to receive and why that specific valve. Even in those subcategories I talked about, there are subtle differences and they apply differently to different human beings. It’s important they understand that.

They also want to determine if they’re eligible for a less traumatic approach, a smaller incision that offers them exactly the same operation. It has to be exactly the same operation. Finally, that they be sure that at that golden moment, that golden opportunity when they’re having heart surgery that the surgeon is addressing every problem they have, whether that be changes in their aorta, the presence of atrial fibrillation, other valves that might be leaky that might need to be repaired. All of those things need to be addressed. That would be my more global advice.

Adam Pick: Dr. Gerdisch, I’ve heard a lot of great things from a lot of clinicians over the years, and hearing about the golden moment when patients are getting ready to go through a heart valve procedure. I’ve never heard it described quite so eloquently, so thank you. I think patients really need to think about that. They need to be 100% confident when they’re being rolled into that operating room that their questions have been answered. If there’s one thing I know, it’s that you answer patient questions incredibly well as you’ve done today, as you’ve done for, I don’t know, the past ten years that we’ve known each other.

Marc, I just want to take a quick second to say thank you and thank your entire team at Franciscan Health for all the wonderful work that you’ve been doing to advance valvular therapy and really take care of patients who need the help that your team provides. Thanks for everything you’re doing, and thanks for being with us today.