Dr. Rishi Anand, MD, Medical Director for the Electrophysiology Laboratory at Holy Cross Hospital talks about an antidote for blood thinners that is being studied to see if it can save lives.
Interview conducted by Ivanhoe Broadcast News in March 2018.
How many people in the US do you estimate need to take blood thinners and why do you need to take blood thinners?
Dr. Anand: Looking at Medicare in the last year or two there’s been well over several hundreds of thousands of patients who are actively taking blood thinners on a yearly basis in the United States. They could be for reasons such as abnormal heart rhymes’ like atrial fibrillation or they could have had a blood clot in their legs and it traveled up to their lungs; we call that a pulmonary embolism. All of those are reasons why people might be on a blood thinner like Warfarin or more common the newer ones like Xarelto or Eliquis or Pradaxa.
What are some of the risks of taking blood thinners?
Dr. Anand: When I have a conversation with patients about being on a blood thinner the obvious question that always comes up is, am I going to bleed doctor? And the answer is yes there is a small but real risk that you could bleed. But I always tell these patients would you rather bleed or would you rather have a stroke. It’s the lesser of two evils. We’re always balancing risks and benefits in our patients when we prescribe powerful medications like blood thinners. Invariably most of the patients understand that they don’t want to have a stroke due to their atrial fibrillation or they don’t want to have another blood clot go to their lungs. So they initiate therapy with a blood thinner.
There’s that risk versus benefit type situation. And how would a patient know, like Mr. Bressen, that something is happening? If you are having a bleed how would you know?
Dr. Anand: In general when people start on a blood thinner I typically tell tem them that if you notice any symptoms like you’re feeling faint or people are commenting that you look a little bit paler, or you’re noticing more obvious things like your stools are changing colors. Becoming very dark or have a very foul smell to them; those could be signs that you have some sort of bleeding going on. In Mark Bressen’s case, Mark came to the emergency room feeling extremely weak, very light headed and he looked extremely pale and of course his stool culture changed to a very dark black color. We call that Melena. And when he came in to the hospital we found that he was having a gastrointestinal bleeding or internal bleeding as a result of the blood thinner that we had initiated.
If they’re having this type of bleeding, how critical is it to get help right away?
Dr. Anand: There is some data looked at from Medicare, you know when patients come in acutely to an emergency room with either an acute gastrointestinal bleed or let’s say they have a bleed in the brain, their thirty day mortality for these types of patients can be anywhere from ten percent to upwards of thirty five to forty percent within thirty days. That means in English there’s a chance of death within thirty days with these acute medical illnesses. And that’s based on looking at data from the Medicare data base of patients back in two thousand and sixteen. Clearly there is a very strong need to be able to take care of these patients, to be able to stop their bleeding so we can mitigate or reduce the likelihood of death or worsening of the hospitalization.
This is where this clinical trial comes in to play, tell us about the clinical trial and the medication being used.
Dr. Anand: Let me give a little background history. Coumadin is a generic blood thinner that has been on the market for many, many years and in the last decade there have been new comers to the market which we call novel oral anticoagulants. Some examples are Xarelto, Eliquis or Pradaxa. Now medication specifically Xarelto and Eliquis do not have an antidote available to them as of yet. People are taking these blood thinners and they come in with a bleeding event we don’t have any specific agent to date that we can use to reverse the blood thinner immediately. Contrast that to Coumadin: if you come in with a bleeding event we can give you Vitamin K which is a typical antidote that’s used to try to reverse Coumadin immediately. Along with other types of blood products that we use to reverse Coumadin. And Pradaxa which is a novel oral anticoagulant but works through a different mechanism than Xarelto or Eliquis, it also has an antidote that just got released to the market about a year ago. The two medications that I’m specifically talking about Xarelto and Eliquis to date have no antidote. Xarelto and Eliquis are the top two prescribed anticoagulants in the United States. There is clearly a very strong need to develop an antidote for these two particular medications and any other medications that act through a similar mechanism.
And that’s where this medication is being tested, tell us about the study and the name of the drug and how it is being administered.
Dr. Anand: Sure. At Holy Cross Hospital at the Jim Moran Heart and Vascular Research Center we have had the opportunity to participate in what I consider to be a groundbreaking, and will be a landmark trial where we have access to an antidote for drugs like Xarelto and Eliquis for people who come in with acute major bleeding episodes. The name of the drug is Andexanet alfa and it’s a protein molecule that is specifically engineered to act as a decoy for people who are on medications like Eliquis or Xarelto. We would then administer the medication with an IV bolus followed thereafter by an IV infusion of the drug. The antidote reverses the Xarelto within two to five minutes. As soon as somebody comes in with a bleeding episode we’re able to reverse that Xarelto or reverse that Eliquis in two to five minutes with our antidote. Not many other centers in the United States have access to it. We’re proud to say that because of our efforts in research and ongoing efforts we’re able to access some of the cutting edge medical therapies that are available.
Once these patients like Mr. Bressen gets this medication, are they fine?
Dr. Anand: The name of the trial is the ANNEXA-4 trial and it is the seminal trial that will, in my opinion, allow the medication to be assessed by the FDA and eventually released to the United States consumer market for use with patients who come in with acute bleeding. To date we have reversed well over two hundred and some odd patients nationwide. At Holy Cross we’ve reversed approximately fourteen to fifteen patients who’ve come in emergently. To give you perspective we’re one of the higher enrollers study site in the trial. And we’ve had the opportunity of actually presenting some of our data to the FDA as they deliberate the medication and access its merits and make a decision on whether or not it can be released to the United States market. As a principle investigator for the trial I am hopeful. I have seen nothing but good things for people who are coming with very bad situations. And I’m hopeful that this medication will make it to the market.
In Mark’s case I know he has a procedure coming up, he will have to be on blood thinners. Can these patients then go back on blood thinners but in maybe a lesser dosage?
Dr. Anand: Mark’s case is pretty unique. Mark has a history of atrial fibrillation and it’s for that reason we put him on a blood thinner because we don’t want him to have a stroke due to the atrial fibrillation. After getting started on the blood thinner he experienced a very significant gastrointestinal bleed that required us to transfuse blood to him. We were able to reverse him with the antidote and now the question is, well he still needs to be on some sort of blood thinning to protect him from having a stoke. But clearly if we do that we run the risk of him bleeding again. We also have access to something called a watchman device. It’s a device that we implant in the heart specifically in the left atrium and within the left atrial appendage. It’s a little pouch inside of the heart where ninety percent of the strokes come from. And once we implant this device it seals that pouch off from the rest of the heart and prevents strokes from dislodging from the pouch and going to the rest of the body to create a stroke. We’re advising him to undergo a watchman implant procedure so that way he can have the benefit of being protected from having a stroke without having to be on the dangers of being on a chronic blood thinner.
Would you say that this drug did save his life?
Dr. Anand: With respect to Mark when he came in we quickly accessed that he was having a GI bleed and he was given the antidote Andexanet alfa and we reversed his bleeding. We reversed the Eliquis effect that he had, the blood thinning effect within two to five minutes. And I would say yes that this drug along with the rest of the team was critical in saving his life.
This is an antidote only for Eliquis; and the second one?
Dr. Anand: Andexanet alfa is an antidote or reversal agent for people who are taking Factor Ten A inhibitors which are types of blood thinners. Specific examples of Factor Ten A inhibitors are Eliquis, Xarelto and Savaysa. These are the three common drugs on the market today that would qualify for reversal or being reversed or being revered by Andexanet alfa.
Do feel this is groundbreaking and this could be fast tracked through the FDA?
Dr. Anand: Andexanet alfa has been designated as a breakthrough therapy by the FDA, which in essence means that the FDA is reviewing that process very quickly and trying to get this drug to market. Obviously with safety in mind for the United States population. At Holy Cross not only do we practice the standard of care but because we’re involved with research and we’re on the cutting edge of technology we’re able to go above and beyond the standard of care and offer patients treatments and therapies that in other situations and other institutes they just may not have access to.
Any risks to the medication that we know of?
Dr. Anand: There are risks with the medication.
It’s good to have at least there is this. When we have no other choice it saves lives.
Dr. Anand: With all investigational studies that we perform there are always risks with each of them. And we go through the risks and benefits with all the patients. In this particular case and things that I have seen we’ve had the opportunity reversing fourteen to fifteen patients. And they can be from anything as minor as just an IV reaction site to something as major as an allergic reaction or a blood clot. But we balance that risk with the benefit of trying to stop an acute major bleeding episode.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Christine C. Walker, Media Relations
Christine.Walker@holy-cross.com
954-958-4893
Rishi Anand, MD
954-772-2136
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