Live Shingles Vaccine and Waning Immunity; Semaglutide and CV Events

— Also in TTHealthWatch: sodium and blood pressure; aspirin and LVADs

by Rick Lange, MD, Texas Tech; Elizabeth Tracey, Johns Hopkins Medicine

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, 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.

This week’s topics include aspirin and left ventricular assist devices, semaglutide and cardiovascular events in people without diabetes, sodium and blood pressure, and live shingles vaccine and waning immunity.

Program notes:

0:42 Semaglutide and cardiovascular outcomes
1:42 Once weekly subcutaneous semaglutide or placebo
2:42 Does reduce cardiovascular events
3:42 Side effects at initiation and escalation
4:14 Dietary sodium and blood pressure
5:16 About 8 mm Hg systolic
6:16 All groups ended with a benefit
7:17 You can read on the label
7:32 Live herpes zoster vaccine
8:32 34% vaccinated
9:32 Vaccinated prior to 2017
10:05 Making mechanical cardiac support safer
11:05 Risk of bleeding or clotting
12:10 End

Transcript:

Elizabeth: Semaglutide and cardiovascular outcomes in obesity in people who don’t have diabetes.

Rick: The effect of salt on blood pressure.

Elizabeth: The live herpes zoster vaccine and 10 years of follow-up.

Rick: And making mechanical cardiac support safer.

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

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

Elizabeth: Let’s remind everybody, Rick, that this week the American Heart Association meeting has been providing us with an enormous amount of information and so I’d like to turn first to the New England Journal of Medicine. This is the look at semaglutide, which is a diabetes drug, cardiovascular outcomes in people with obesity who do not have diabetes.

Previous research has already established that if you do have diabetes, this semaglutide, which is a glucagon-like peptide-1 receptor agonist or GLP-1 receptor agonist, has been shown to reduce adverse cardiovascular events. In this case, what they did is they looked at people who did not have diabetes but who did have obesity — is this going to help as far as cardiovascular outcomes are concerned?

It’s a multicenter, double-blind, randomized, placebo-controlled, event-driven, superiority trial. They have patients 45 years or older who had preexisting cardiovascular disease and a BMI [body mass index] of 27 or greater, but no history of diabetes. These folks were randomly assigned 1:1 to either receive once-weekly subcutaneous semaglutide or placebo.

The primary cardiovascular endpoint was composite of deaths from cardiovascular causes, non-fatal MIs [myocardial infarctions], non-fatal stroke in a time-to-first-event analysis. They also looked, of course, at safety.

They had 17,000+ patients enrolled, 8,800 of whom were assigned to the semaglutide arm. The mean duration of exposure was 34 months and they followed them for 39.8±9.4 months. What they found was that this primary outcome occurred in 6.5% of the semaglutide group and in 8% in the placebo group.

Rick: I want to highlight again the patient population we’re talking about. You mentioned the fact they don’t have diabetes but they did have obesity, and more importantly they all had established cardiovascular disease. They had a previous heart attack or a previous stroke, or they had symptomatic peripheral arterial disease.

I think the study is very convincing that in this group of individuals that it does reduce cardiovascular events. We don’t yet know whether in the absence of established cardiovascular disease whether GLP-1 agonists would be useful or not.

The other caveat about this is that only about a fourth of the individuals were women and very few African Americans — 4% of the patient population. I think we needed additional data before we’re giving this to everybody.

Now, the last thing I had mentioned is the average weight reduction was about 10%. However, the cardiac benefits were established long before all the weight was lost. It decreased C-reactive protein, it decreased inflammation, it decreased blood pressure, so there may be some other effects for the GLP-1 agonist besides just weight reduction that are beneficial in reducing cardiovascular disease.

Elizabeth: One of the things I thought was interesting that they speculate on is this gastrointestinal side effects. They talk about that nausea, vomiting, and diarrhea were not uncommon during treatment with these particular receptor agonists, especially when they initiated treatment and as they escalated the dose. The question is whether that’s going to end up being tolerable over the long haul for people.

Rick: Yeah. Elizabeth, notably, as you mentioned, about one out of six individuals that were started on this were unable to tolerate it. By the way, they didn’t start at the highest dose. They started at a low dose and tried to titrate people up. Even with, one out of six were unable to tolerate it.

Elizabeth: Yeah. I think, of course, we’re going to see a whole lot more of these types of agents that are going to be out there — no doubt some that are going to try to overcome that particular side effect.

Rick: Let’s talk about the effect of what I call salt — actually dietary sodium — on blood pressure. We’ve talked before about the fact that dietary sodium recommendations are really still highly debated, especially among people that are already taking a blood pressure medication. Is there any benefit to putting someone on a low-salt or low-sodium diet?

This was a really well-done study in 213 individuals between the ages of 50 and 75. A fourth of them had normal blood pressure, about 20% had controlled high blood pressure, about 30% had uncontrolled hypertension, and about 25% had untreated hypertension.

They randomized them to take a high-sodium diet for a week — that’s 2,200 mg [added daily]; i.e., about one teaspoon of salt — or low-sodium, where it was 500 mg, about one-fourth of a teaspoon. The same individuals, some got low-sodium, then high; and some got high-sodium, then low-sodium diet. They just looked at what the changes in blood pressure were during that time period.

The difference between the high-sodium and low-sodium diet was about 8 mm Hg systolic. That is remarkable. In fact, that’s as much or more than what you get with putting someone on our first-line antihypertensive agents. This group of individuals shows that, really, dietary sodium reduction significantly lowers blood pressure in the majority — that was in three-fourths — of middle to elderly adults.

Elizabeth: I think this is a truly remarkable study in JAMA in light of all the many times that we’ve talked about dietary sodium and its impact on blood pressure because we’ve seen results that have been kind of all over the map, and this also seems like it happened really quickly in this modification of diet.

Rick: You’re right, Elizabeth. A couple of things. One is this just a 1-week diet, where they took people on a normal diet and put them on a high-salt diet, it didn’t change the blood pressure very much. That’s because we already take too much salt in our diet. However, when they put them on the low-salt diet, it dramatically decreased really in 1 week.

By the way, I talked about the different groups that were studied. It didn’t matter whether you were on blood pressure medicine or not, whether you were normotensive or hypertensive, controlled or out of control — all the groups end up with the same benefit with putting people on a low-salt diet.

Elizabeth: I have to go back to some of the questions that we have identified in the past and those are that we are accustomed to certain tastes in our foods and eliminating sodium, particularly in prepared foods, has always been kind of a real challenge. How are we going to manage that?

Rick: First of all, we shouldn’t be adding salt. Secondly, we ought to be looking at the salt intake of the foods that we’re eating. Foods that are not prepared at home, foods that are ultra-processed, oftentimes have a high-salt intake. Now, most food products indicate how much sodium is in them, even processed or already prepared foods.

Elizabeth: I’m wondering about regulatory bodies that might take this on as at least an advocacy position that sodium somehow has to be reduced in prepared foods.

Rick: I would not disagree with you. I think it’s going to be a tough sell to do that. We have individuals that are trying to get the government to regulate fewer things, but at least knowing you can read on a label to figure out whether this is high salt or not is really incredibly important. But as you mentioned, this is a fairly short study — in 1 week there was dramatic changes. It doesn’t address the issue of if we sustained this over a long period of time are those blood pressure changes still sustained.

Elizabeth: Let’s turn to The BMJ. This is a look at the live herpes zoster vaccine in 10 years following vaccination. This, of course, is an important issue because recrudescence of herpes zoster actually results in shingles. Shingles is a big public health problem, particularly in people who are immunocompromised and in folks as they age.

This is a Kaiser Permanente Northern California study. It looks at more than 1.5 million people who were age 50 years and older, and they were followed for a composite of almost 9.4 million person-years. They were looking at vaccine effectiveness in preventing herpes zoster postherpetic neuralgia, which is a huge problem, this persistent pain after people have an outbreak. Herpes zoster ophthalmicus, of course, can result in blindness and frankly admission to the hospital for fulminant zoster infection.

Of their 1.5 million people, 34% were vaccinated with the live herpes zoster vaccine. They said how did your resistance to all of these things change over time? Vaccine effectiveness waned from 67% in the first year to 15% after 10 years. They look at all of these other things — the postherpetic neuralgia, herpes zoster ophthalmicus, and hospitalization — all of them waned.

Across all their follow-up time, their overall vaccine effectiveness was 46%. I think what we need to note is that now, here in this country, we have a recombinant vaccine so we’re not using the same vaccine anymore, although elsewhere in the world they continue to use this one.

Rick: The live zoster vaccine was the first vaccine against shingles, and over 50 million people have received it. In the United States, it was licensed in 2006. The recombinant one that you mentioned was devised to try to prevent some of this waning effects. It didn’t become available in the U.S. until 2017, so individuals that were vaccinated prior to 2017 in the U.S. or elsewhere undoubtedly got the live virus.

As you mentioned, the effects wane; therefore individuals that haven’t received the recombinant should seriously consider doing that. We know that that is now delivered in a two-dose vaccination scheme. It’s about 98% effective in preventing shingles and if you prevent shingles you can prevent the side effects as well.

Elizabeth: Indeed, because you really don’t want all of the sequelae that follow recrudescence of this infection.

Rick: Yeah. As you mentioned, we have listeners around the world and the live vaccine is still used in the United Kingdom and Australia.

Elizabeth: Finally, let’s turn back to JAMA.

Rick: Elizabeth, I tee this up as making mechanical cardiac support safer. These are devices called left ventricular assist devices or LVADs and they are placed in individuals that have heart failure. We originally used them as a bridge, where you put in a left ventricular assist device to get them to transplant. Well, now these devices are actually destination. This isn’t waiting for transplant. This is really their therapy. Because of the risk of stroke, people got put on aspirin and an oral anticoagulant called Coumadin [warfarin] that causes potentially bleeding side effects.

What’s happened now is the device has become much better, what are known as fully mechanically levitated devices, and that decreases the risk of clotting. The question is do we still need to have that intensive anticoagulation?

To address that, they looked at over 600 patients with heart failure that had one of these left ventricular assist devices. Half of them they treated with Coumadin and aspirin, and the other half they treated with just Coumadin alone. They followed them to see over the next year what was the risk of either have a bleeding or a clot formed. Removing the aspirin did not increase the risk of any clots forming, but it did decrease the risk of bleeding by about 34%. This is great.

Elizabeth: Speaking of safer, we’ve got agents that are used in place of warfarin or Coumadin all over the place. What are we doing still using that in this particular population?

Rick: Well, Elizabeth, it’s interesting, because although these newer anticoagulants are better than Coumadin in some circumstances, in others they are not. Particularly when someone has a mechanical valve put in, we keep them on Coumadin because there is a lower risk of having a clot form. In this case, again, it’s a mechanical device. We have great experience with Coumadin and no experience that the newer anticoagulants are any safer.

Elizabeth: It sounds like for right now it’s really good because you get to take fewer drugs rather than more.

Rick: And without increasing the risk of stroke or having clots form, but decreasing the bleeding risk and that’s always important when people have mechanical devices.

Elizabeth: On that note then, 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.


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