Skip to main content

Clot-Busting Drugs

As many as 100-thousand Americans die every year from pulmonary embolism – a blood clot to the lung. Traditionally, doctors treat pulmonary embolism with blood thinning medications, which slowly relieve the symptoms-like shortness of breath. But new research shows that for some patients, a different approach can have life-saving results.

"We like to travel – we like the shore." Rosalie O'Neil told Ivanhoe.

Beach trips like this destination wedding almost weren't possible for Rosalie O'Neil this year.

 "I was feeling more congestion every day," said O'Neil, "It was getting a little worse."

After two weeks of suffering through what she thought was the flu – Rosalie went to the emergency room.

"We could see her heart was racing. Her heart rate was double what it should have been." Jay Giri, M.D., Interventional Cardiologist at the University of Pennsylvania told Ivanhoe.

"They did a PET scan, and that's where they found blood clots in both lungs," said O'Neil.

In addition to the traditional blood thinning medication, Dr. Giri also offered Rosalie clot-busting drugs.

"Dr. Giri said if you decide to do it, tomorrow you will breathe much better," said O'Neil, "and he was right."  

Doctors traditionally reserve clot-busting drugs for the very sickest patients, because of the risk of bleeding to the brain.

Doctor Giri and his colleagues analyzed the results of previous trials of the clot-busting drugs- and found adding the drugs to traditional therapy reduced deaths by forty-seven percent.  Low risk patients did fine with only the traditional therapy. High-risk patients needed the clot-busting drugs. The big difference? The twenty percent of patient's in-between.

"There was a benefit to treating intermediate risk patients with clot-busters," said Dr. Giri.

Rosalie was in that middle group.  She says the additional therapy got her back to the things she enjoys most- surf and sand with family and friends.

Dr. Giri says the use of clot-busting drugs is still a hotly-debated topic, but this study shows the benefits of offering the therapy to additional patients.  Dr. Giri says the best candidates for the clot-busting drugs are younger than 65, with little to no risk of bleeding.  He says additional research is needed to help doctors better tailor pulmonary embolism treatments to the individual patient.

BACKGROUND: Pulmonary Embolisms (PE) typically start with a blood clot in the leg, which may end up traveling to an artery that supplies the lungs. This is why many of the standard symptoms are usually in the chest region: breathing problems, chest pain, etc. Prevention of blood clots leading to PE can be as simple as exercising or moving around after extended periods of mobility, i.e.: long airplane/car trips, or after surgeries or illness that require bed rest. Occasionally, but rarely, other substances can cause blood clots: air bubbles, tissue from a tumor, or bone marrow fat from a broken bone.

(Source: http://www.nhlbi.nih.gov/health/health-topics/topics/pe/causes.html, http://www.nhlbi.nih.gov/health/health-topics/topics/pe/signs.html, http://www.nhlbi.nih.gov/health/health-topics/topics/pe/prevention.html, http://www.mayoclinic.org/diseases-conditions/pulmonary-embolism/basics/causes/con-20022849)   

TREATMENT: The first obvious treatment for PE is administering anticoagulants (blood thinners); however, there are other alternatives. A vein filter can be placed in the vena cava, the vein that carries blood from the body back to the heart, to prevent blood clots from traveling to the lungs; it does not prevent new clots from forming.  Compression stockings are a non-invasive method to prevent the root of blood clots, deep vein thrombosis. The pressure keeps blood from pooling/clotting, reducing chronic swelling that a blood clot may cause.

(Source: http://www.nhlbi.nih.gov/health/health-topics/topics/pe/treatment.html)

NEW TECHNOLOGY: Thrombolytics (Clot-busters), usually reserved for life-threatening situations, are able to dissolve clots more quickly. In a research study by Dr. Jay Giri, an interventional cardiologist at the University of Pennsylvania Health System, along with colleagues, found that patients using clot-busters in addition to blood-thinning medication had a lower mortality rate (2.17) than those taking only blood-thinners (3.89). Future research will focus on the impact of dosage and method of medicine administration to discover optimal benefits with minimal risks – in this case, excess bleeding. Patients younger than 65 may be at less of a risk for bleeding, which is why they make ideal candidates for this treatment.

(Source: http://www.mayoclinic.org/diseases-conditions/pulmonary-embolism/basics/treatment/con-20022849, http://www.uphs.upenn.edu/news/News_Releases/2014/06/giri/print.html)

FOR MORE INFORMATION ON THIS REPORT, PLEASE CONTACT:

Lee Ann Donegan

Media Relations

University of Pennsylvania Health System

215-349-5660

Leeann.donegan@uphs.upenn.edu

If this story or any other Ivanhoe story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Marjorie Bekaert Thomas at mthomas@ivanhoe.com

Jay Giri, M.D., Interventional Cardiologist at the University of Pennsylvania focused on Interventional Cardiology and Vascular Medicine discusses a new way to help treat patients with pulmonary embolism.


I wanted to ask you a little bit about the study, what did you look at?

Dr. Giri: What we sought to examine was what the best treatment strategy is for patients who present with pulmonary embolism. A pulmonary embolism is this process where a blood clot actually moves from the leg, it forms in the leg, and it goes up to the lung and sometimes it gets lodged in the lung and sometimes can cause life-threatening even symptoms.

How common is this, for pulmonary embolism how often does this happen?

Dr. Giri: So pulmonary embolism is actually a very common cause of serious illness and even death in America. Over a hundred thousand patients a year present to hospitals with pulmonary embolism. And that's in America alone.

So you said in this study you are looking to determine the best treatment, tell me a little bit about what kind of factors, what exactly did you look at?

Dr. Giri: Yes, what we tried to compare was how patients who come in with pulmonary embolism should be treated. Traditionally therapies for pulmonary embolism had involved logically blood thinning medications. The idea is a blood clot stuck in your lungs, you're going to go ahead and give someone blood thinners, allow that blood clot to slowly break down over time. And the honest truth of it is that's absolutely the right answer for the majority of patients who come in with pulmonary embolism. However, some patients who come in with pulmonary embolism come in very sick. And those patients often times those little blood thinning medications aren't enough to take them out of harm's way. And in those patients there are more powerful therapies available. Specifically there are powerful clot busting medicines which do more than just in the blood they actively break up the clot and cause it to dissipate. And we do reserve those therapies classically for our patients who have the most severe forms of pulmonary embolism.

For this kind of the treatment who's your ideal candidate, whose your best patient?

Dr. Giri: So the ideal patient to be treated with the blood clot busting medicine, blood clot busting medicine, would be somebody who's relatively young, who doesn't have a lot a risk for bleeding and they come in with what's called a severe pulmonary embolism. And by that I mean that their blood pressure is dropping, they're not breathing well and they are in a position where they actually could die from the pulmonary embolism. And those patients when you give them these clot busting medications they've been shown even in the past as well as in our study to have to have lifesaving effects.

It would seem like common sense if this is the best way to go why is that not gold standard, why is that not just the way you treat patients?

Dr. Giri: So the problem with these clot busting medications is there's a benefit which we already talked about, about breaking up the blood clots. But there's also a risk and the obvious risk is of bleeding. They're so powerful that they can cause people to bleed and in the worst cases, the thing we most fear is for patients to spontaneously bleed in to their head and that can be a life-threatening problem of its own. So we're constantly on the edge here as doctors who are taking care of pulmonary embolism patients of trying to make the right call of who should get a clot busting medicine. And we're trying to weigh what their chances are of having a catastrophic head bleed versus the chance of their pulmonary embolism being so bad that they could die from that.

Is it a matter of like a more careful screening process, I guess I'll ask you what do you do to narrow it down so that you know you're treating the right patients?

Dr. Giri: The first thing is knowledge on the part of the physicians that we're trying – when we approach these patients pulmonary embolism we generally break them up into three groups. They are what we call low risk, intermediate risk and high risk groups so it's pretty easy. We judge their risk based on basically what they're blood pressures are and whether they have any signs of their heart being under strain from the pulmonary embolism.  Whether their heart is under such strain that it's not pumping blood appropriately through the circulation and when we see that the heart is under strain that automatically raises the risk of the patient. So those patients who are low risk they don't have any heart strain and they may have some shortness of breath and chest pain but they're going to do just fine with the classic therapies. And that's most patients who come in with pulmonary embolism, probably at least seventy percent. There are a small percentage of patients, probably five percent, who are so sick that they're almost actively dying in front of you when they're coming in the door. Those patients are going to need more aggressive therapies whether that's a clot busting medication or even sometimes open chest surgery to try to get that clot out of there. Then there's this group in the middle, that gray zone and that's where the controversy really lies that you alluded to. And those patients in the middle are tough because on the one hand they're not actually showing you signs that they're going to imminently die however, there's no question that their hearts are under strain.  And that's about twenty percent of patients come in, in that kind of scenario.

Tell me a little bit about what you studied then.

Dr. Giri: So what we tried to look at was all of the studies that have ever been done of this issue. We basically looked at every time that a randomized trial was conducted where they took patients and they flipped a coin and they said half of you are going to get blood thinning medication and half of you are going to get a clot busting medication for the treatment of pulmonary embolism. Believe it or not this question has been asked sixteen different times over the last forty years. Unfortunately every single study that's asked it has been relatively small. Unlike in disease processes like heart attack or stroke there hasn't been the same degree of attention by both researchers and the public on this other life-threatening vascular disease, pulmonary embolism. So all of these small studies on their own couldn't give us a clear answer. So what we did is we put all sixteen of those studies together and we looked at a few, conglomerate all that data, we looked at it as a whole what would you now see. And could you say anything numerically about risks and benefits of use of clot busting medications in these three groups of patients the low risk, intermediate risk and the high risk.

And when you looked at all those numbers?

Dr. Giri: The most important things we saw were that we agreed absolutely that low-risk patients should be treated in the general way. And we also agreed that the guidelines regarding high risk patients for more aggressive therapies were indicated. But what we found which was new was that there was a benefit to treating intermediate risk patients with clot busters.

Talk to me about the clock busters. Are there a certain number of hours, you had mentioned if the patient  had been having trouble for more than a week it's not going to be a benefit.

Dr. Giri: So there's no question that we know that the longer that the pulmonary embolism have been sitting there the less effective the clot busters are going to be. And in those cases you have less effect but you're still exposing the patient to potential risks. So guidelines would say that if patients are greater than two weeks after their onset of symptoms of shortness of breath it's probably wisest to hold off on using clot busting medications. And I would agree with those guidelines. In these studies the clot busters were used in patients who were presenting always within hours to days of their pulmonary embolism. So were talking about patients who recognize their shortness of breath and present to the hospital with it. Usually the symptoms are so severe that patients do come in.

What's the next step after you do a study like this? What does this prove or what does this kind of lay the groundwork for?

Dr. Giri: I think the single most important two questions coming forward are one, is when you use a clot busting medication who is going to bleed from it and number two, who is going to benefit from it. And we showed in broad stroke that there are probably a greater proportion of patients who could benefit from this therapy than had previously been recognize. However, if you're that person and you're that doctor that has to make that decision in the individual patient it still is a difficult decision and I would never deny that. So what we're seeking to do going forward is to come up with clinical risk scores to try to advise physicians of factors that might make their patients more likely to bleed into their head with use of the clot busting medication. And in that case you would withhold it. And on the other hand we might be able also look into factors in the future of those patients who derive particular benefit. Right now the thing we've seen is what might be common sense and that's that younger patients tend to do a little bit better with clot busters than older patients.

When you talk about clinical risk scores is that like a set of questions or criteria to come up with a really good set of questions?

Dr. Giri: That's exactly right. So different things you might think of are I just mentioned age so potentially age could be a factor which clearly delineates who could—who might be more likely to bleed or not. Other factors that people come in with like a history of having issues with a stroke in the past or issues related to some medications use that they're on. None of this has actually been figured out well in the medical research to this point to try to really zone in on whose most going to benefit by using clot busting medicine because right now physicians still feel wary of using them and I think rightfully so in a broad range of patients.

I'm going to ask just a question that may clarify for our viewers, when you say this is a brain bleed some people may know exactly what that means and some may (not)-- well what does that mean, it sounds bad; what does that do?

Dr. Giri: What it means is that spontaneously patients can have small vessel, a small blood vessel in their head start to bleed. And unfortunately the head is the single worst place where that can happen because there is no space for that to bleed out into. If you bled into your arm it would just cause a little bruise. But a bruise on your arm is no big deal a bruise on the brain is a very, very big deal. And that can result in disability, the need for neurosurgery and even death. So that's something that we are very wary of. So when we're trying balance these risks and benefits we know that the big risk is of when you use these clot buster medications is that some patients are going to be at risk of that brain bleed. The thing we haven't seen with pulmonary embolism treatment in particularly is what the biggest driving risk factors are for that. And I think that we absolutely need to figure that out.

Tell me a little bit about Rosalie, Mrs. O'Neil. You said she seemed to be the perfect candidate. What was it about her condition?

Dr. Giri: So Rosalie I would say is a patient who I looked at when she came in and she was not somebody who was so sick coming in the door that she looked like she was at risk or imminently dying, thank God. However she was in quite a bit of distress. I mean she couldn't even take two steps without being able to breathe well. And we could see her heart was racing and her heart rate was double what it should have been. We could see that her breathing wasn't perfect, that her oxygen levels were low when we measured them. We could see that when we did the cardiac ultrasound that her heart was under strain and half of her heart was not moving well at all because it could not push through this terrible blood clot that was sitting in her lung. And then I looked at her and I said listen -- this is a woman who has not had any kind of major surgeries or anything to start this process in the past. This kind of came out of the blue. She was a relatively young woman in our experience she was under the age of the age of sixty five, which we've shown in our study is kind of a clear-cut point for one patient may be at higher risk of bleeding. When you put that altogether and I saw just how symptomatic she was and how much distress she was in, I talked to her and we had a conversation where I said there's two different ways of handling this. It seems to me that you're somebody who would actually benefit a more aggressive strategy where we give you clot busting medications and if they're successful you're going to be feeling good within a couple hours. On the other hand a more conservative approach would be to kind of give the traditional blood thinning medicines and hope that over days to weeks your symptoms kind of slowly resolve. And after that discussion we made that decision together to go with the clot busters because she had a lot of risk factors for having problems with her heart and lungs. And also not many risk factors or no risk factors whatsoever for bleeding. So when you put those two things together the risk benefits seemed to favor using the clot busters in her. So she's that patient who was in the gray area that would be managed differently in different places. But definitely in her case sustained benefit from our therapies.

Is there anything I didn't ask you that you think people would like to know?

Dr. Giri: Yeah I think that the big picture that I would like to convey is obviously the majority of patients with pulmonary embolism should be treated the traditional way which is with blood thinning medication. However for patients who come in with some high risk feature by think that experienced clinicians who have experience with pulmonary embolism's have to be taken care these patients and be able to clearly make these decisions to balance this tough risk benefit decision in the individual patient for whether to deliver clot busters or not.

What is the clot busting medication?

Dr. Giri: There's a few of them.  In America the two most common used are called Alteplase and Tenecteplase. In America, Alteplase is the most commonly used and in Europe Connectaplase is the most commonly used although both have been used in both places.

Is that what TPA is?

Dr. Giri: TPA is Alteplase.

TPA where does that come from?

Dr. Giri: Tissue Plasminogen Activator.

This was just published in the journal right?

Dr. Giri: Exactly yeah. We published our findings in the Journal of American Medical Association last month. And they've been received with the amount controversy that you might expect which is that there's a lot of doctors who had a very strong opinion in the gray area patients. These therapies should never be considered in them. So we did raise some awareness that there's probably a subgroup at least of those gray area patients who these therapies will benefit those patients.

So in the letters that you're getting, some support and some people, are you getting beaten up a little bit?

Dr. Giri: Absolutely, I've had letters from both sides where I've had doctors who are experts in the field who have e-mailed me and said, thanks for publishing this and then put some messages on Twitter and the whole nine yards. And there have also been some doctors who have, you know, criticized us for maybe pushing things a little too fast, too far in this area. And to those physicians I would say I actually a hundred percent agree that what we did is we raised the specter that we need to have more of all hands on deck approach really tackling pulmonary embolism with the same type of efforts that we've made with heart attacks and stroke. That pulmonary embolism is you know in a lot of ways the overlooked vascular killer.

Why is that?

Dr. Giri: That's a good question I think that not the same amount of research money has been put into it and it's not something with which people are – doctors, patients, are as aware of. It doesn't look as scary to them as a heart attack or stroke. So I'm hoping that the societies and the government, NIH and everybody steps up and starts really getting behind research efforts into pulmonary embolism.

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.


Loading...