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 best medicines for atrial fibrillation when a stent is used, an envelope for cardiac devices to reduce infection risk, psychosis and ADHD medicines, and eggs and cardiovascular disease.
0:54 Eggs and cardiovascular outcomes and death
1:53 Linear relationship with consumption
2:50 Egg consumption associated with other unhealthy behaviors in past
3:56 Tied more to cholesterol
4:34 Cardiac device envelope
5:35 Mesh material with antibiotics
6:36 ADHD medicines and psychosis
7:36 Twice as high in the amphetamine group
8:40 0.1 to 0.2% of patients
9:20 One in five people with a-fib need a stent
10:27 Safest anticlotting was apixiban
Elizabeth Tracey: Are eggs really associated with cardiovascular disease and death?
Rick Lange, MD: Making pacemaker placement safer.
Elizabeth: What’s the relationship between psychosis and medicines for ADHD?
Rick: The appropriate blood-thinning therapy for people that have atrial fibrillation and need a stent.
Elizabeth: That’s what we’re talking about this week on PodMed TT, your weekly look at 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 March 22nd, 2019.
Rick: I’m Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso, where I’m Dean of the Paul L. Foster School of Medicine. Elizabeth, if you hear some background noise, I’m recording in an airport at DFW.
Elizabeth: Let’s hope they don’t do any of those annoying overhead kind of announcements [LAUGHTER] which are really loud. Why don’t we start first, I think I’d like to start, anyway, with the study that’s relative to the consumption of eggs. I don’t know, Rick. In our 15 years of podcasting, it’s unclear to me how many times we’ve talked about this issue. I know at least a couple because a person at Hopkins, Peter Kwiterovich, appeared to have answered this question pretty decisively some time ago. I know we talked about his research and here we are again looking at it again.
In this particular analysis, they pooled data from six different studies and the total included 29,615 participants. They had a mean follow up or median follow up of 17.5 years. They took a look at the association of dietary cholesterol or egg consumption with incident cardiovascular disease and all-cause mortality. Basically, what they came up with was that each additional 300 milligrams of dietary cholesterol consumed per day was significantly associated with higher risk of incident cardiovascular disease and all-cause mortality. This was a linear relationship.
This looks like, once again, we need to pay closer attention to how many eggs we’re consuming. This pooling was called something I was unfamiliar with — The Lifetime Risk Pooling Project — to take a look at this data from these six studies that we’ve talked about exhaustively in the past.
The thing that was also different in this study was that these associations, they took a look at potential confounders. In their discussion, they said, “We’ve been having this talk for a long time, but previous studies didn’t really account for all the potential confounders.” In this case, they did and those included other lifestyle factors and other dietary factors. They feel like this is a fairly robust, although not huge, association.
Rick: I think it’s probably one of the better studies, and every time we report, the studies get a little bit better. Almost 30,000 people followed for over 17 years. As you notice, the egg consumption in the past has been associated with other unhealthy lifestyle behaviors such as low physical activity or smoking or unhealthy dietary patterns. Even cholesterol consumption in the past has been associated with other foods that have a lot of unsaturated fat and animal proteins.
What this study does is it builds upon the other studies. It included a comprehensive assessment of all of those factors, and so we’re able to isolate the role of both cholesterol and egg consumption not just in soft endpoints, but in hard endpoints. That is cardiovascular disease and mortality. The other thing that is even [more] convincing is that the egg consumption related to mortality seems to be related to its cholesterol content and nothing more. That confirms the other finding that cholesterol does contribute to cardiovascular disease and mortality.
Elizabeth: Admittedly, one of the things that they talk about in this study, also, is that eggs are a really good source of protein and they’re not very expensive, so that’s another thing. If we take a look at energy relative to the production of an egg as a food source, it’s significantly less than it is for other high-protein sources. I guess I’m a little concerned about this impugning of eggs as a dietary staple, if you will, relative to this cholesterol relationship.
Rick: It’s tied more to the cholesterol than the egg consumption. When we talk about 300 milligrams of cholesterol, we’re talking about two eggs a day. Currently, in the American diet, about 25% of the cholesterol comes from eggs and about 42% from meat. However we reduce our cholesterol, [such as] by watching the foods we eat, will lower our cardiovascular mortality.
Elizabeth: Are you suggesting that paying more attention to the meat might be a good idea?
Rick: I think cholesterol, no matter how it’s ingested.
Elizabeth: Since we’ve just concluded the American College of Cardiology meeting, of course, other studies this week are relative to cardiology. Which one would you like to start with?
Rick: Let’s talk about this pacemaker — or actually, it’s an implantable cardiac device, because it could be a pacemaker or a defibrillator. These are devices that are typically put underneath the skin, usually underneath the clavicle, and their indications are if somebody needs a pacemaker to make their heart rhythm more appropriate, or a defibrillator to prevent them from having ventricular tachycardia and death, and these devices are fairly common. There will be about 1.5 million patients who will receive these devices worldwide each year, but when you implant these devices, they always have a risk of infection associated with it.
Despite the fact that we give antibiotics before the procedure, we use sterile technique, and there have been a number of different techniques trying to lower that risk of infection, because when it gets infected, oftentimes, the device has to come out and the leads have to come out, and that carries a significant risk in about 1% to 2% of individuals.
What this study did was it took the implantable device and put it inside an envelope. It’s a wire mesh envelope that has antibiotics impregnated in it in almost 7,000 patients that were having an implantable device. Half of them had the device put in this mesh material and had it put underneath the skin. The other half had it done in a routine fashion. What they discovered was that using this antibiotic impregnated envelope decreased the risk of infection by about 40%. That’s immediate. Then if you look at long-term results, infections over the next 12 months, it decreased to right about 37%.
Elizabeth: I really like this study, too. We should note that it was published in the New England Journal of Medicine. Would you be suspicious that over the long haul there might be an increased risk of other potential adverse events? I’m thinking about things like even fibrosis that would develop around the mesh.
Rick: Elizabeth, that’s a good point. They looked at acute infections and they followed these patients up for at least a year. Over the 12 months, there was no increased risk associated with it at all. I would expect that if we’re going to see a complication we’d see within the first 12 months. We’ll follow these patients for a longer period of time, but the preliminary data looked very good.
Elizabeth: Yeah, and some way to get our arms around this infection rate, which is really important. Staying in the New England Journal of Medicine, but switching out of cardiology, then, let’s go to my second one this week, which is a look at the stimulants methylphenidate, an amphetamine for the treatment of ADHD in children. In this case, it’s in adolescents and young adults. This is a really important issue because there’s a relationship with psychosis relative to these medicines, and this was something that was a little novel for me. I was not aware of that. Were you, previously?
Rick: No, I wasn’t, Elizabeth.
Elizabeth: They used data from two commercial insurance claims databases to look at patients 13 to 25 years of age who received the diagnosis of ADHD and who started taking either methylphenidate or amphetamine for that indication. There were 337,919 adolescents and young adults in this particular analysis. Actually, the study population consisted of 221,000+ who actually took the medicines. Of those, about half were taking methylphenidate and half were taking the amphetamines.
At the end of the day, while the rate was really low, it was actually twice as high in the amphetamine group as it was in the methylphenidate group. I thought the editorial was noteworthy that in the U.S. it turns out that amphetamines are used more often, where in Europe, methylphenidate is used more often. I think that if we’re trying to reduce even this really small risk of psychosis development in these folks it may be better to go ahead and switch to methylphenidate instead.
Rick: The other thing that’s worth mentioning, Elizabeth, is that the psychotic episode didn’t occur usually within the first several days or even weeks. It usually occurred several months. In fact, about 4 months after exposure to the medication. Now the nice thing about this is that once it’s recognized, the psychotic symptoms, first of all, they’re short lived and they resolve after discontinuing the medicine in about 92% of the patients even without treatment with any antipsychotic medications.
But your point is well taken. If a person started on an amphetamine and develops psychosis, then they ought to be switched to methylphenidate. The other thing we don’t know is if the person is receiving methylphenidate and develops psychosis will it happen on an amphetamine? But at least there are two different choices. Fortunately, it happens relatively infrequently. It was 0.1% to 0.2% of individuals treated with these medications.
Elizabeth: That’s the good news. I guess one of the other things in this study that they noted is that it was not possible to determine apriori who might develop psychosis secondary to the use of this medicine.
Rick: That’s a good point. It’d be nice if we could predict the risk and it’d be nice to happen fairly early on. But, again, what I want our listeners to understand is it happens infrequently, usually months afterwards and it is reversible.
Elizabeth: Let’s turn to your final one, again, sticking with the New England Journal of Medicine.
Rick: This comes out of the recent heart meetings. In about 1 in 5 individuals that have atrial fibrillation, the irregular heart rhythm that’s oftentimes treated with a blood-thinning agent to prevent a stroke, they’re subsequently going to need to have a stent, or [they] have what’s called an acute coronary syndrome. That is a near heart attack that requires them to have a stent. Usually when we put a stent in, we use antiplatelet agents, usually two of them. In the person that has atrial fibrillation and a stent, they could end up on both antiplatelet agents and anticlotting agents called antithrombotic agents. That increases the risk of bleeding.
What’s the safest regimen to use in these individuals? The investigators looked at over 4,600 patients from 33 countries that all had atrial fibrillation and subsequently needed to have a stent put in. They randomized them to what’s called a “2×2” trial. With regard to the blood thinner, they either put them on the old standard, coumadin, or one of the newer agents called apixaban. In the second part, they put them on either aspirin or a placebo. By the way, all these were getting another antiplatelet agent called a P2Y12 inhibitor, usually clopidogrel.
When they did all their analysis, here’s what they found. The safest anticlotting agent was apixaban. Secondly is do you need to add aspirin to these blood-thinning agents when the patient is already receiving clopidogrel? The addition of aspirin caused increased bleeding, and it didn’t significantly reduce the risk of what’s called ischemic symptoms, that is a heart attack or another acute coronary syndrome. In essence, what this means is probably the safest regimen in most individuals is to use apixaban and one of the P2Y12 inhibitors like clopidogrel to avoid coumadin and to avoid aspirin after the first week.
Elizabeth: That’s sounding like a take home in many venues that we’ve talked about recently, both the avoidance of coumadin and the avoidance of aspirin. I guess I have to ask, though, what about side effects relative to this strategy?
Rick: The side effect is, actually, a reduced risk of bleeding because the more intensive the anticoagulation regimen increases the risk of bleeding. Then with apixaban versus coumadin, it’s easier, I’m going to say, to regulate it because you don’t have to follow the blood numbers, and you’re more likely to be in a therapeutic range with apixaban than you are with coumadin.
Elizabeth: And it’s a lot more expensive, however.
Rick: It is more expensive. There’s no question about it. Fortunately, most insurance companies cover it, again, because the outcome is better and it also avoids the patient having to have frequent blood draws to measure whether their blood is adequately thinned or not.
Elizabeth: Then, on that note, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.
Rick: I’m Rick Lange. Y’all listen up and make healthy choices.