Triple Inhaler for Asthma; Hypothermia After Cardiac Arrest: It’s PodMed Double T!

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PodMed Double T is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary.

This week’s topics include hypothermia after cardiac arrest, eating red meat, two drugs for people with diabetes and heart disease, and a triple inhaler for asthma.

Program notes:

0:50 Red meat consumption

1:51 Low certainty evidence only

2:51 Only randomized controlled trial

3:51 Don’t have very good evidence

4:40 Uncontrolled asthma treatment

5:40 Triple therapy over a year

6:42 Cooling people down after cardiac arrest

7:47 A modest survival benefit

8:47 More likely to have minimal or moderate neurologic function

9:40 Aspirin and ticagrelor in people with diabetes

10:40 Do they benefit from two agents?

11:40 Inexpensive and effective

12:44 End

Transcript:

Elizabeth Tracey: What is the impact on health of consuming red meat?

Rick Lange, MD: A new option for uncontrolled asthma.

Elizabeth: Should we cool down people who’ve had certain kinds of heart attacks?

Rick: And do people with diabetes and known heart disease need to take another antiplatelet agent besides aspirin?

Elizabeth: That’s what we’re talking about this week on PodMed TT, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a medical journalist at Johns Hopkins, and this will be posted on October 4, 2019.

Rick: And I’m Rick Lange, president of the Texas Tech University Health Sciences Center in El Paso, where I’m also dean of the Paul L. Foster School of Medicine.

Elizabeth: And also has a bit of a cold having just returned from France, so welcome back!

Rick: Sorry about the raspy voice, but I’m eager to record with you. Where do you want to start, Elizabeth?

Elizabeth: I think we should start with Annals of Internal Medicine, this issue of red meat consumption. I actually wanted to go through all of the headlines I’ve read about in this study this week because the media take on it has really been quite interesting.

This was a meta-analysis. They took a look at randomized trials only where an assessment of red meat products in diets were part of the randomized, controlled trial. When they surveyed the literature, they only found 12 eligible trials and actually included only a single trial, the Women’s Health Initiative, when they talked about their conclusions, as being the only one that actually was credible. They said, “How much red meat are you eating? How does that impact on a number of different health outcomes?” That was the only one that explicitly recorded their consumption of both unprocessed red meat and processed red meats.

Here’s where they made their conclusion. They said low-certainty evidence from the Women’s Health Initiative trial showed that a diet lower in red meat may have little or no impact on all-cause mortality. They said the certainty of the evidence was rated down for a metric I was unfamiliar with called serious indirectness, some things that I’m not familiar with. Maybe you can help me with that.

They found this consumption of red meat also was not impactful with regard to cancer, having little or no effect on cancer mortality. There were slight improvements in quality of life and HDL cholesterol, but these effects were very small. They did say that they thought this was the only trial that was thought to have trustworthy results, and all the rest of them proved to be at high risk for bias or because of lack of blinding and substantial missing participant outcome data.

My view of this is OK, this is the only randomized, controlled trial. It really does not refute substantially all the other previous observational trials that have said we should really reduce our consumption of red meat, and the media spin on this has been, “Maybe you can go ahead and eat your red and processed meats,” and that’s not a conclusion I would agree with.

Rick: I think you’re right. These authors tried to be very rigorous. By the way, in this randomized trial, it was in postmenopausal women. It didn’t randomize women to either more red meat or less red meat. It was a randomized trial, and during that randomization, they assessed their intake of red meat over that time period. They weren’t randomized to different diets. That’s the first thing.

Most of the data we get regarding our diet comes from observational studies. What you’d like to do is take a population and have several hundred thousand people on one diet, [and] the other hundred thousand people, randomize them to a different diet, and follow them over 20 years. That’s just not very practical, so most of our data comes from observational studies, but I would agree with the authors, not with the media take. If you look at randomized trials, we don’t have very good evidence and that’s because the trials weren’t designed to do that. So I totally agree with you. The message isn’t, “You can eat red meat or unprocessed meat with impunity.” The message is, when you look at randomized trials, the data just aren’t there to support a conclusion in either direction. I think you’re absolutely right about that.

Elizabeth: And I guess I would also say there is compelling evidence with regard to environmental impact and resource devotion, the production of red meat and processed meat products is very impactful with regard to that. So on no other basis, if that, I would say, “Eat less red meat.”

Rick: I think you can argue that on many different levels, but again, on the basis of what we both would acknowledge are observational studies, but for the most part, very good studies nevertheless.

Elizabeth: OK. Which of yours would you like to turn to?

Rick: Let’s talk about uncontrolled asthma treatment.

Elizabeth: That’s in the Lancet.

Rick: That affects about 40% of individuals that have asthma. When I say uncontrolled, the conventional treatment is to use inhalers, oftentimes with steroids, and then if it’s still not well controlled is to combine that steroid with a beta agonist. You can get that in a single inhaler, but even 40% of individuals on that therapy continue to have moderate-to-severe exacerbations of asthma over the subsequent years. There’s a third type of agent called a muscarinic agonist. It’s a different receptor. It also dilates the bronchi as well, and you can get that in a different inhaler. What about putting all three of them in a single inhaler, and is that better than having just two of the agents together?

So this is a really extraordinary study in that it combined two trials, one in which people were on medium-dose steroids and the other in which people were on high-dose steroids and a beta agonist, and still had uncontrolled asthma. They were randomized to either continue that therapy or use the triple therapy: prednisone, a beta agonist, and a muscarinic agonist. And they followed them over the course of a year. Those that received the triple therapy in a single inhaler had better lung function, but more importantly, it decreased the risk of having a severe or moderate asthma exacerbation by 15% with no adverse side effects. It makes it easier to take, increases compliance, it improves outcome, and there’s no adverse effects, so this is good news.

Elizabeth: We know that people who have acute and sometimes even moderate exacerbations of their asthma, especially if that’s concomitant with flu infection or pneumonia or what have you, that can be life-threatening. So as far as I’m concerned, being able to manage this a priori sounds like a great strategy.

Rick: What our listeners need to be aware of is it doesn’t make the quality of life or your breathing necessarily any better at the time you’re taking an inhaler, but what this does is it prevents future exacerbations, and that’s the major benefit. Now, I’d be remiss if I didn’t say that also, in addition to this, there are biologic agents that are available for specific patients that have, for example, high antibodies to IgE. Oftentimes, those we can decrease the steroid dose.

Elizabeth: On to the New England Journal of Medicine, a look at whether cooling people down after they’ve had cardiac arrest actually improves survival and their neurological function. This has been an ongoing issue. We’ve talked about it so many times, this issue of hypothermia or cooling folks down in these situations. In this case, this is in people who’ve had cardiac arrest with a non-shockable rhythm or asystole. Their heart is just not working at all. In addition to that, there were a lot of exclusion criteria for people to be enrolled in this particular study, which was in France.

They had almost 600 people who were randomized to either be in the hypothermia group, and this was moderate hypothermia of 33 degrees Centigrade for 24 hours when they were in that non-shockable rhythm state and identified. They followed these folks out to 90 days. At that time, 29 out of 284 in the hypothermia group were alive with a score that they considered to be reasonable, 1 or 2 with regard to their neurological function, while 17 out of 297 in the normothermia group were alive at Day 90 in that same state. So basically, they come to what I’m going to call kind of a tepid, and I don’t mean that to be with regard to temperature any kind of a pun, conclusion that yeah, it does seem to help modestly.

Rick: When we talk about cardiac arrest with non-shockable rhythm, what that means is when you come upon someone that has a cardiac arrest and, for example, you put an AED (automatic external defibrillator) on them and it senses the rhythm, if there’s a particular rhythm, it can shock at will, because the shock can actually restore normal rhythm. In these particular cases, people did not have a rhythm that the shock would be beneficial. What that means is oftentimes these are non-cardiac causes for arrest. We called it a cardiac arrest. How can you have a non-cardiac cause? Let’s say someone has excessive bleeding, for example, or may have had sepsis or pulmonary embolism.

This is the first study to show whether hypothermia helps those individuals, and as you said, there was a modest benefit. Those that received hypothermia were more likely to survive with either minimal or moderate neurologic disability. That was 10% versus those that had normal temperature of 5.7%. You’re right. It’s a very modest benefit. There was no difference, by the way, in mortality at 90 days.

Elizabeth: I want to ask you because you, of course, have all these clinical exposures, how problematic it is to render them hypothermic. I guess one of my conclusions is, is this like chicken soup? It can’t “hoit” [hurt], so why not just go ahead and employ it if it’s not that big a deal.

Rick: You’re absolutely right. It won’t necessarily hurt and there is a very modest benefit, but not all facilities have access to it. The most important thing, by the way, for cardiac arrest is to initiate CPR as quickly as possible. Get the individuals to a center that has as much expertise as possible.

Elizabeth: OK. Let’s turn to your final one also in the New England Journal of Medicine.

Rick: We know that aspirin is beneficial in many patients that have cardiac disease or are at risk for cardiac disease. Now besides aspirin, there are other antiplatelet agents that are a little bit more effective: clopidogrel, prasugrel, and ticagrelor. The question is in which individuals should they receive aspirin, which we know is effective and is relatively inexpensive, and when should we add another antiplatelet agent? We know that individuals that have a heart attack or an impending heart attack, those that have an acute coronary syndrome, benefit from having two antiplatelet agents. We know those that have a recent stent put in, they benefit from it as well.

But what about other high-risk groups? In the past, it looked at people with stroke. They don’t receive benefit from having two antiplatelet agents. What about those with peripheral arterial disease? They don’t benefit. What about those with a heart attack in the past? They don’t benefit. The last group to look at is those that have diabetes and known coronary artery disease, that is they had a stent or a bypass in the past or they’ve had a picture that demonstrated they have a blockage. Do they benefit from having two antiplatelet agents? That’s what this study assessed.

They did it in over 19,000 patients, so this was a really big study. They randomized them to either aspirin or aspirin plus ticagrelor and they followed them for a median of about 40 months. There was a little bit less incidence of heart events, about a 1% difference between those that received aspirin and both agents. But on the other hand, the risk of bleeding and intracranial bleeding was higher, about 1%. So when you look at what’s called irreversible harm, that is death from a heart attack or a stroke or fatal bleeding or an intracranial hemorrhage, there was no difference between the two. That suggests that diabetics, even those that have known coronary artery disease, benefit from aspirin, but don’t benefit from the addition of another antiplatelet agent.

Elizabeth: And that’s another issue, of course, we’ve been circling around for many years, and it, at least, makes me feel like that’s great because aspirin is cheap. We have abundant experience with it, and those are always good things as far as I’m concerned.

Rick: You’re right. It’s inexpensive. It’s easily available and it’s very effective in patients that have coronary disease or [are] at high risk of coronary disease like diabetics. Anybody that’s considering aspirin needs to look at the risk and benefit. The higher the risk of having a heart attack or stroke, the more benefit. If there’s less of a chance of that, then obviously the risk of GI bleeding or other bleeding with aspirin, the harm associated with that could overweigh any benefit. That’s why it’s important to weigh the risk and benefit. These are studies that have been going on for a number of years trying to identify which patients benefit from the most potent antiplatelet effects, that is two agents, and it appears to be those that either have a stent put in or those that have an impending or ongoing heart attack.

Elizabeth: OK. On that note, that is a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.

2019-10-05T14:00:00-0400

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