Controlling Hypertension After Intracerebral Hemorrhage; Treating Acute Sinusitis

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 Texas Tech Health El Paso, look at the top medical stories of the week.

This week’s topics include a polypill for hypertension following stroke, clinical impact of rapid tests for gram-negative bloodstream infections, is there any remaining role for nirmatrelvir-ritonavir (Paxlovid), and treating acute sinusitis.

Program notes:

0:30 Controlling hypertension after intracerebral hemorrhage

1:30 Triple pill or placebo

2:30 Only effective treatment is lowering blood pressure

3:32 Serum creatinine levels

4:15 Is there a role for nirmatrelvir-ritonavir?

5:15 Did not reduce hospitalization or death

6:10 Fast antimicrobial susceptibility test for gram-negative

7:10 Desirability of outcome ranking (DOOR)

8:10 Median time to effective therapy reduced

9:10 Was not superior

10:07 Acute sinusitis treatment

11:15 Secondary effects higher with augmentin

12:21 End

Transcript:

Elizabeth: Controlling blood pressure after intracerebral hemorrhage.

Rick: Antibiotic treatment of acute sinusitis.

Elizabeth: Rapid tests for gram-negative infections.

Rick: And is there still a role of Paxlovid in the treatment of COVID-19?

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: And I’m Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: Rick, how about if we turn first to the New England Journal of Medicine? I’d like to start with this controlling hypertension after someone has had an intracerebral hemorrhage, a stroke. And this, of course, is a really important issue because it’s important before strokes. And then afterwards, it’s even more critical in some respects to prevent another one.

In this study, they took a look at patients who had a history of having had an intracerebral hemorrhage previously. They entered the trial if their systolic blood pressure was between 130 and 160 mmHg at baseline, and they were clinically stable. They did a 2-week run-in phase of controlling hypertension after this hemorrhagic stroke using a 3-agent pill: telmisartan at 20 mg, amlodipine at 2.5 mg, and indapamide at 1.25 mg. So a triple pill, a polypill. And they were randomly assigned to continue receiving the triple pill or to receive a matching placebo.

The primary outcome was the first recurrent stroke and, of course, numbers of secondary outcomes, including their blood pressure control, cardiovascular events, death from cardiovascular causes, and safety. They had 833 patients in the triple-pill group and 837 receiving placebo.

They showed that this recurrent stroke occurred in 4.6% of the folks in the triple-pill group and in 7.4% in the placebo group. They also had a pretty pronounced impact on their systolic blood pressure. Cardiovascular events were significantly lower in those who took the polypill. There was also an increase in serum creatinine levels. It sounds really compelling to try this polypill because this is such an important outcome. And the other outcome that wasn’t impacted by this was all-cause mortality.

Rick: We know that if you had an intracranial hemorrhage or intracerebral hemorrhage, the only effective treatment for preventing a second one is lowering your blood pressure. Nothing else works. When we do that effectively, we decrease the risk of intracerebral hemorrhage and mortality related to it. How best to do that?

These investigators took a pill that had 3 different antihypertensive, 3 different pathways: an angiotensin receptor blocker, a calcium channel blocker, and a diuretic. And those that could tolerate it, it could lower the risk of the things that we mentioned. Now, could tolerate it. Remember, they had a 2-week run-in. They gave it to individuals. Those that couldn’t tolerate it — those that had hypotension, those that had an increase in creatinine — were never put on it. And that was about a fourth of patients.

For those that did, they had a better blood pressure lowering than those that were just on a single agent. And by the way, this was conducted in 12 different countries, places where intensive control of blood pressure may not otherwise be undertaken. It’s just that this particular pill did a better job of lowering blood pressure than what they were already doing. Still good news because you can increase compliance if you can take all this in one pill instead of trying to get someone to take 3 different pills, especially if you can make it affordable.

Elizabeth: And, of course, we have that number needed to treat to prevent one stroke was 35, so that’s a pretty compelling number. I thought it was interesting that they noted on this increase in serum creatinine levels that there’s new evidence that suggests that such changes in serum creatinine levels are predominantly the result of a hemodynamic response and not necessarily associated with long-term progression of kidney disease. I think that that’s an important point.

Rick: It is. You have to screen people upfront, though, again, to make sure that the increase in creatinine, because there are some other effects associated with that in terms of how one handles electrolytes like potassium and magnesium, and other things. But I agree with you. It’s a hemodynamic effect, and it’s not a direct kidney effect that would cause chronic kidney disease. I agree. Very convincing efficacy.

Elizabeth: Staying in the New England Journal of Medicine then?

Rick: Is there a role for Paxlovid? It’s a two-agent antiviral that is given to individuals that may have COVID infection. It’s been tested previously in two different populations. One is normal-risk patients and high-risk patients — those that are immunocompromised, those that are old, those that have heart disease, diabetes, chronic kidney disease, obesity. Giving Paxlovid to those individuals that are not vaccinated decreased the risk of death and hospitalization.

Fast-forward now, where almost everybody has either been exposed or they’ve been vaccinated many times, vaccinated multiple times. Now the question is, in those individuals, high-risk, previously vaccinated or infected, is Paxlovid helpful? And by the way, this is important because I have patients that call me and say, “Do I need to take Paxlovid because I have a COVID infection?”

They enrolled a total of over 4,200 individuals. They were over the age of 50, considered to be high-risk. They had had COVID for less than 5 days, and they put them on Paxlovid twice a day and looked at the incidence of death and hospitalization. What they discovered is that Paxlovid did not reduce the incidence of hospitalization or death among these individuals. I’m not sure there’s a role for Paxlovid at all any more.

Elizabeth: And that’s, of course, good news because it does have some side effects.

Rick: It does. In fact, almost everybody had some side effect, usually gastrointestinal or a difference in taste. There were some that had severe reactions. Most of them were minor. But you’re right. If it’s not helpful at all, you shouldn’t be exposed to any risk at all.

Elizabeth: Well, I will have to say, though, that I think it was quite a success story, or at least it was helpful, when we were having all the multiple variants of COVID coming across the transom and people were not uniformly vaccinated. So it was a success story for that.

Rick: It was, but it’s like most therapies; it’s targeting toward the group that receives either the most or any benefit.

Elizabeth: We like those things that you get to give a miss to.

Let’s turn then to JAMA, a fast antimicrobial susceptibility test for gram-negative bacteremia. This is called the FAST randomized clinical trial. If you’ve got somebody who’s got bacteremia, is it helpful to use one of these rapid antimicrobial susceptibility tests, or ASTs, compared with standard tests when the suspicion is it’s gram-negative bacilli?

They looked at patients who lived in areas where there is a high prevalence of antimicrobial resistance and the causative organisms are normally gram-negative. This also is an international study with centers in Greece, India, Israel, and Spain. They looked at hospitalized patients with bloodstream infections that were caused by gram-negatives, and they looked at the utility of this rapid test versus just their standard testing.

They used this metric that I’m completely unfamiliar with. That is the acronym DOOR, D-O-O-R. That’s the desirability of outcome rankings. And there’s 3 categories in that: alive without deleterious events, alive with deleterious events, and death. This has been previously validated according to the authors. That was the primary outcome. Secondary outcomes included their 30-day mortality, length of hospitalization, ICU admission, acquisition of additional hospital-acquired infections, and a couple of other things. They had 850 patients included in their primary analysis.

The probability that the DOOR outcome was more favorable in the rapid testing group was 48.8% and their previously established threshold was 50%. Their median time to effective antibiotic therapy was not different between the groups in the randomized population. However, there were other metrics that were different. Their median time to antibiotic escalation or de-escalation was faster in that rapid group by 14 hours. And their median time to effective therapy was 9.5 hours in the rapid-testing group versus 28 hours in the standard-testing group.

Because they had that previously established threshold of 50%, they conclude that this rapid testing was not superior to standard testing. However, the editorialist disagrees with that and says that this is pretty compelling evidence that we ought to be using this thing to make sure that we’re employing the right antibiotic therapy.

Rick: Aside from this fast testing, you have to get the blood, you have to identify the organism, it takes a while to grow, and then identify which antibiotics that might be susceptible, and that may take 2 or 3 or 4 days. And this fast testing, one can get within minutes after the person with sepsis has presented.

This DOOR outcome, I mean, basically what they’re saying is, “Okay, the major outcome you’d like is, are you alive? Two is, did you have a clinical response? Well, after that, were you discharged? And lastly, are there any deleterious effects?” So it’s ranking from most to least important. And I have to agree with the authors on this. There was really no difference between the two. It was not superior.

One of the reasons he said it may not have been superior is, let’s say, you identify the organism, you know what it’s susceptible to. If you don’t have the right antibiotics to treat the patient with, it doesn’t really matter. And in some of these countries, they didn’t have access. I can understand why the editorials will say, well, it may have a place, but it only has a place if it can change therapy.

Elizabeth: The editorialist points out that these antibiotic stewardship programs are activated in this whole paradigm of, hey, how are we going to treat this patient? And opines that if we have a tool that will help those antibiotic stewardship programs support clinicians and optimizing therapy faster, then we ought to be doing it.

Rick: Hypothetically, that’s great. But we would have predicted that we’d have better outcomes. And what we’re saying is, well, we really actually don’t have any better outcomes. That should be tested. And then one needs to look at the cost effectiveness as well, especially in countries that have limited resources. Is this the best place to put their resources? I don’t think it’s ready for primetime yet.

Elizabeth: Then let’s go on to yours, which is also in JAMA.

Rick: Acute sinusitis is associated with the highest rate of antibiotic prescribing in the U.S. for adults aged 18 to 65. They’re oftentimes treated with either amoxicillin or amoxicillin combined with clavulanate, which is a beta-lactamase inhibitor that’s supposed to extend the antimicrobial coverage to organisms that are resistant to amoxicillin, which often goes by the name Augmentin. Is one better than the other?

It was a retrospective cohort study. They used a nationwide healthcare utilization database. They identified individuals that got treated with antibiotics. Did those individuals need to go on to a second antibiotic? Did they have complications or did they need to be hospitalized? And they compared those that received amoxicillin versus those that received Augmentin. They included over 500,000 eligible patients.

And what they found out is that treatment failure occurred in about 3% of patients overall and 0.03% had an emergency department visit or inpatient encounter. And by the way, it was no different between amoxicillin and Augmentin. No difference between the two.

Elizabeth: What about side effects and what about cost?

Rick: They’re relatively inexpensive because they’re generics, but the risk of secondary effects was higher for Augmentin than for amoxicillin. This has included yeast infections and C. diff, less than 1.5% for both of those combined. About 50% fewer secondary infections with amoxicillin.

Elizabeth: I’m just going to mention that one of the studies that we rejected for this week was one that was taking a look at the impact of any antibiotic use whatsoever on the gut flora. And I think we’re going to be seeing a whole lot more about that. I’m wondering about that with regard to these two different agents.

Rick: Yeah. I can’t address that, but your point’s well taken. Let’s use targeted antibiotic therapy that if we can narrowly focus on whatever we’re treating, that’s better overall. I agree with you, Elizabeth.

Elizabeth: On that note then, that’s 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.

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