Reteplase Bests Alteplase for Early Reperfusion in Acute Ischaemic Stroke

 Can't tell if this is good enough from what's being reported in this abstract.

Reteplase Bests Alteplase for Early Reperfusion in Acute Ischaemic Stroke

By Gabrielle Mostello

Reteplase is more likely than alteplase to result in an excellent functional outcome in patients with acute ischaemic stroke(Excellent is 100% recovery, did it do that?), according to a study published in The New England Journal of Medicine.

Alteplase is currently the standard agent used in early reperfusion therapy; however, since demand has increased significantly, alternative thrombolytic agents are needed.

For the current study, Shuya Li, MD, Beijing Tiantan Hospital, Beijing, China, and colleagues randomised patients with ischaemic stroke within 4.5 hours after symptom onset 1:1 to receive a bolus of intravenous reteplase 18 mg followed 30 minutes later by a second bolus of 18 mg (n = 707) or intravenous alteplase at 0.9 mg/kg of body weight up to a maximum dose of 90 mg (n = 705).

The researchers found that 79.5% of patients who received reteplase had an excellent functional outcome(Excellent is 100% recovery, did it do that?) compared with 70.4% of those who received alteplase (risk ratio [RR] = 1.13; 95% confidence interval [CI], 1.05-1.21; P < .001 for noninferiority and P = .002 for superiority).

Within 36 hours of disease onset, the incidence of symptomatic intracranial haemorrhage was similar between the 2 groups, occurring in 2.4% of patients in the reteplase group and 2% of those in the alteplase group (RR = 1.21; 95% CI, 0.54-2.75).

At 90 days, the incidence of any intracranial haemorrhage was higher with reteplase than with alteplase (7.7% vs 4.9%; RR = 1.59; 95% CI, 1.00-2.51), as was the incidence of adverse events (91.6% vs 82.4%; RR = 1.11; 95% CI, 1.03-1.20).

The researchers acknowledged several limitations to the study, including its open-label design, enrollment limited to Chinese adults, and under-representation of women. Furthermore, patients aged ≥80 years and patients eligible for thrombectomy were excluded.

“In patients with acute ischaemic stroke who were eligible for intravenous thrombolysis within 4.5 hours after the onset of symptoms, reteplase [is] more likely to result in an excellent functional outcome than alteplase,” the researchers concluded.

Reference: https://www.nejm.org/doi/full/10.1056/NEJMoa2400314

SOURCE: The New England Journal of Medicine

Drugs Go Head to Head for Ischemic Stroke

Does your competent/ doctor and hospital have enough functioning brain cells to know about this and implement it if found useful? Go and ask them before you need this!

Drugs Go Head to Head for Ischemic Stroke

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 expanding the window for treating ischemic stroke, new agents for treating ischemic stroke, managing obesity in children and adolescents, and preventing surgical site infections.

Program notes:

0:36 Expanding the window for treating ischemic strokeopens in a new tab or window

1:33 Complete recovery 10% more

2:33 Routine CT scanning

2:44 Comparing two agents to treat ischemic stroke

3:44 More in the reteplase group had hemorrhage

Transcript:

Elizabeth: Better agents for treating acute ischemic stroke.

Rick: Expanding the time to treat stroke.

Elizabeth: Treating childhood and adolescent obesity.

Rick: And preventing surgical-site infections.

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: Rick, I'm going to turn it to you. Which of these would you like to start with?

Rick: Well, Elizabeth, there were two studies that had to do with stroke, so let me cover the first one. This is an article in the New England Journal of Medicine, a study that was done with the thought of can we increase the time to treat strokes. This study took place in China and they ask a simple question. We know if we treat strokes with tenecteplase, one of these agents that dissolves clots, in the first 4.5 hours you get a good result. We know that if you give a thrombectomy -- and that's done in other countries -- you get a good result. But what about individuals that you do an imaging study and it looks like there is still brain that's viable, but it's been more than 4.5 hours outside the typical window? If you give tenecteplase, do you receive a good outcome?

Five-hundred and sixteen patients, the stroke that occurred more than 4.5 hours after the symptoms presented up to as long as 24 hours. But with a scan, it looked like there was still some part of the brain that was viable. What they discovered was that there was a higher percentage of individuals that had complete recovery with treatment with this agent than in those that didn't receive it. In fact, it was about a 10% absolute difference, more individuals that had complete recovery.

Is there an increased risk of bleeding? There was a slight increased risk of what's called symptomatic intracranial hemorrhage within 36 hours. It was about 3% for those that received the agent versus 0.8% for those that did not. This is important, Elizabeth, because about two-thirds of the patients that present following stroke present after that 4.5-hour window.

Elizabeth: Clearly relying on imaging in order to assess the viability of the brain tissue that's impacted by the stroke. In the absence of the ability to do that kind of imaging, I'm wondering what's the utility of this agent.

Rick: This study certainly doesn't address that. Many of these studies in China were done in hospitals that were relatively rural and almost every hospital has a CT scanner. They showed it didn't need any special equipment, just routine CT scanning. Now, again, these are hospitals that didn't have access to thrombectomy and in that setting extending the time window further out isn't really beneficial.

Elizabeth: Let's turn then to the other article that's in NEJM also looking at the management of stroke, acute ischemic stroke, which is of course what we're talking about, the most common type. This is comparing an agent called reteplase versus alteplase [Activase], which is an agent we've had a lot of familiarity with in their efficacy and in these outcomes.

They had a total of 707 who were assigned to receive reteplase and 705 received alteplase. There is a difference in the administration. The reteplase is intravenous, a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg, and the alteplase is a single dose. They were looking at their efficacy outcome, excellent functional outcome, which is a score of 0 or 1 on the Modified Rankin Scale, and they also looked at symptomatic intracranial hemorrhage within 36 hours after symptom onset.

They did see the intracranial hemorrhage within 36 hours in 2.4% of the 

Transcript:

Elizabeth: Better agents for treating acute ischemic stroke.

Rick: Expanding the time to treat stroke.

Elizabeth: Treating childhood and adolescent obesity.

Rick: And preventing surgical-site infections.

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: Rick, I'm going to turn it to you. Which of these would you like to start with?

Rick: Well, Elizabeth, there were two studies that had to do with stroke, so let me cover the first one. This is an article in the New England Journal of Medicine, a study that was done with the thought of can we increase the time to treat strokes. This study took place in China and they ask a simple question. We know if we treat strokes with tenecteplase, one of these agents that dissolves clots, in the first 4.5 hours you get a good result. We know that if you give a thrombectomy -- and that's done in other countries -- you get a good result. But what about individuals that you do an imaging study and it looks like there is still brain that's viable, but it's been more than 4.5 hours outside the typical window? If you give tenecteplase, do you receive a good outcome?

Five-hundred and sixteen patients, the stroke that occurred more than 4.5 hours after the symptoms presented up to as long as 24 hours. But with a scan, it looked like there was still some part of the brain that was viable. What they discovered was that there was a higher percentage of individuals that had complete recovery with treatment with this agent than in those that didn't receive it. In fact, it was about a 10% absolute difference, more individuals that had complete recovery.

Is there an increased risk of bleeding? There was a slight increased risk of what's called symptomatic intracranial hemorrhage within 36 hours. It was about 3% for those that received the agent versus 0.8% for those that did not. This is important, Elizabeth, because about two-thirds of the patients that present following stroke present after that 4.5-hour window.

Elizabeth: Clearly relying on imaging in order to assess the viability of the brain tissue that's impacted by the stroke. In the absence of the ability to do that kind of imaging, I'm wondering what's the utility of this agent.

Rick: This study certainly doesn't address that. Many of these studies in China were done in hospitals that were relatively rural and almost every hospital has a CT scanner. They showed it didn't need any special equipment, just routine CT scanning. Now, again, these are hospitals that didn't have access to thrombectomy and in that setting extending the time window further out isn't really beneficial.

Elizabeth: Let's turn then to the other article that's in NEJM also looking at the management of stroke, acute ischemic stroke, which is of course what we're talking about, the most common type. This is comparing an agent called reteplase versus alteplase [Activase], which is an agent we've had a lot of familiarity with in their efficacy and in these outcomes.

They had a total of 707 who were assigned to receive reteplase and 705 received alteplase. There is a difference in the administration. The reteplase is intravenous, a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg, and the alteplase is a single dose. They were looking at their efficacy outcome, excellent functional outcome, which is a score of 0 or 1 on the Modified Rankin Scale, and they also looked at symptomatic intracranial hemorrhage within 36 hours after symptom onset.

They did see the intracranial hemorrhage within 36 hours in 2.4% of the reteplase group and 2.0% in the alteplase. At 90 days, it was higher in the reteplase group, that's 7.7%, versus almost 5% in the alteplase group. However, with regard to this functional outcome, an excellent functional outcome was achieved in almost 80% of the patients in the reteplase group and in just about 70% of those in the alteplase group. Their conclusion is that this agent is well worth trying.

Rick: This is nice for people who treat strokes. If you just give a single agent, it dissolves the clot, but a clot can reform and there may be some benefit towards giving an agent twice. There was an increased risk of intracranial hemorrhage, but it wasn't symptomatic. That is they could see it on a scan, but it didn't seem to worsen symptoms. That's why the overall outcome was better with the double-dosing agent than the single-dosing agent.

Elizabeth: Right. One question I had about this, of course, is what would have happened if we had dosed alteplase in the same method as the reteplase was dosed?

Rick: The dosing is based upon what we use for treating heart attacks, and so the benefit of the alteplase supposedly is you just give one single dose. You don't have to worry about a double dose. We don't have any experience with double-dosing alteplase at this particular time, not with heart attacks or with strokes.

Elizabeth: I just wonder. The authors assert that we have a need for more of these agents and I'm just wondering, really, is that true or can we just use the ones that we have, but just use them differently?

Rick: I think you're right. What we're doing is we're refining this. Trying to improve the efficacy without increasing the bleeding risk is where the sweet spot lies.

group and 2.0% in the alteplase. At 90 days, it was higher in the reteplase group, that's 7.7%, versus almost 5% in the alteplase group. However, with regard to this functional outcome, an excellent functional outcome was achieved in almost 80% of the patients in the reteplase group and in just about 70% of those in the alteplase group. Their conclusion is that this agent is well worth trying.

Rick: This is nice for people who treat strokes. If you just give a single agent, it dissolves the clot, but a clot can reform and there may be some benefit towards giving an agent twice. There was an increased risk of intracranial hemorrhage, but it wasn't symptomatic. That is they could see it on a scan, but it didn't seem to worsen symptoms. That's why the overall outcome was better with the double-dosing agent than the single-dosing agent.

Elizabeth: Right. One question I had about this, of course, is what would have happened if we had dosed alteplase in the same method as the reteplase was dosed?

Rick: The dosing is based upon what we use for treating heart attacks, and so the benefit of the alteplase supposedly is you just give one single dose. You don't have to worry about a double dose. We don't have any experience with double-dosing alteplase at this particular time, not with heart attacks or with strokes.

Elizabeth: I just wonder. The authors assert that we have a need for more of these agents and I'm just wondering, really, is that true or can we just use the ones that we have, but just use them differently?

Rick: I think you're right. What we're doing is we're refining this. Trying to improve the efficacy without increasing the bleeding risk is where the sweet spot lies.