DAPT Maintains Early Neurologic Function in Mild-Moderate Stroke

 NOT GOOD ENOUGH! You do realize survivors want 100% recovery? Not just less early neurologic deterioration! Or don't you ever talk to survivors without using the tyranny of low expectations on them??

DAPT Maintains Early Neurologic Function in Mild-Moderate Stroke

— Do benefits of clopidogrel-aspirin apply when going up a notch in stroke severity?

by Sophie Putka, Enterprise & Investigative Writer, MedPage Today March 13, 2024

In certain patients with mild-to-moderate acute ischemic stroke, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel (Plavix) reduced early neurologic deterioration better than aspirin alone, the Chinese randomized multicenter ATAMIS trialopens in a new tab or window found.

Early neurologic deterioration -- as measured by an increase of 2 or more points on the National Institutes of Health Stroke Scale (NIHSS) at 7 days -- occurred in fewer of those on DAPT (4.8% vs 6.7%, P=0.03), reported Hui-Sheng Chen, MD, of the General Hospital of Northern Theater Command in Shenyang, China, and colleagues in JAMA Neurologyopens in a new tab or window.

Yet there were no differences in secondary endpoints including excellent functional outcome at 90 days, defined as a modified Rankin (mRS) score of 0-1; occurrence of new ischemic or hemorrhagic stroke within 90 days; change in NIHSS score at 14 days; or occurrence of other vascular events or death within 90 days.

Patients in the study were not eligible for intravenous thrombolysis or endovascular therapy, and DAPT or aspirin therapy was initiated within 48 hours of symptom onset.

"Treatment with clopidogrel plus aspirin was superior to aspirin alone(Superior is 100% recovery! Did you get there?) with regard to reducing early neurologic deterioration at 7 days with comparable safety profile," Chen and colleagues concluded.

"Given a lack of improvement of 90-day clinical outcome and the benefit of earlier dual antiplatelet treatment observed in this study," they noted, "future clinical trials focusing on patients with mild-to-moderate stroke presenting within 24 hours of symptom onset are needed."

Current stroke guidelines recommend aspirin monotherapy for patients with mild-to-moderate ischemic stroke. Early neurologic deterioration remains a challenge to overcome in this population, however, and is associated with clinical outcome.

ATAMIS was the first large-scale DAPT trial that enrolled patients with NIHSS scores of 4-10 who were not eligible for intravenous thrombolysis or endovascular therapy.

Notably, investigators tested a brief 10-14 day course of DAPT in order to avoid excess bleeding in patients. Indeed, safety was comparable between the two groups, with a bleeding event rate of 0.7% for the DAPT group and 1% for controls in this study. Nor were there any differences in other adverse events.

Prior work showed that clopidogrel-aspirin treatment quickly turned a benefit of reduced major ischemic eventsopens in a new tab or window compared with aspirin alone for people with high-risk transient ischemic attack (TIA) or minor ischemic stroke (NIHSS score 3 or less), based on a pooling of the CHANCE and POINT trials.

Last year, the ARAMIS trial had shown that DAPT was noninferior to IV alteplaseopens in a new tab or window for people with minor nondisabling strokes, the median NIHSS score being 2 for this group.

For the ATAMIS study, 3,000 patients from 66 Chinese sites were randomized from 2016 to 2022 to either clopidogrel plus aspirin (n=1,541) or aspirin alone (n=1,459).

Patients were included if they were adults with acute ischemic stroke at the time of randomization, had been functioning independently before the stroke, and were enrolled within 48 hours of stroke symptom onset. Patients who met eligibility criteria for thrombolysis or endovascular therapy were given this treatment and excluded from the study. Others with a clear indication for anticoagulation or a history of intracerebral hemorrhage, among other criteria, were excluded.

The clopidogrel group got a loading dose of 300 mg plus 100 mg aspirin, then 75 mg of clopidogrel and 100 mg of aspirin per day from day 2-14, followed by the same doses of clopidogrel or aspirin for days 15-90. The control group was given 100-300 mg aspirin until day 14, followed by 100 mg aspirin per day until day 90.

Crossovers, poor compliance, and other exclusion criteria shrank the randomized trial cohort to a modified intention-to-treat population of 1,502 in the DAPT arm and 1,413 in aspirin monotherapy.

The two treatment groups had well balanced baseline characteristics in both the modified intention-to-treat and per-protocol analyses. Study participants were 64.6% men, with a mean age of 65.9 years, and a mean NIHSS score of 5 at admission.

Chen's group acknowledged that study limitations included an imbalance in sample size between groups, open-label design, and a large proportion of patients with mild neurologic deficit enrolled in the trial. The results cannot be generalized to patients receiving thrombolysis and endovascular treatment, who were excluded, and need to be confirmed in other populations.

• 

  Sophie Putka is an enterprise and investigative writer for MedPage Today. Her work has appeared in the Wall Street Journal, Discover, Business Insider, Inverse, Cannabis Wire, and more. She joined MedPage Today in August of 2021. Follow

Disclosures

Funding for the study came from the Science and Technology Project Plan of Liao Ning Province.

Chen reported no financial conflicts of interest. One co-author reported serving as associate editor for Stroke and on advisory boards for Idorsia and Brainomix.

Primary Source

JAMA Neurology

Source Reference: opens in a new tab or windowChen H, et al "Clopidogrel plus aspirin vs aspirin alone in patients with acute mild to moderate stroke" JAMA Neurol 2024; DOI: 10.1001/jamaneurol.2024.0146.

DAPT Stays Helpful for Minor Stroke Even With Later Presentation, Worse Symptoms

 Once again the research failed to measure 100% recovery. Survivors want 100% recovery! WHY THE FUCK ISN'T THAT YOUR GOAL?

“What's measured, improves.” So said management legend and author Peter F. Drucker 

The latest here:

DAPT Stays Helpful for Minor Stroke Even With Later Presentation, Worse Symptoms

— But a signal of excess bleeding is noted in the INSPIRES trial

by Nicole Lou, Senior Staff Writer, MedPage Today December 27, 2023

The benefit of dual antiplatelet therapy (DAPT) for a minor ischemic stroke seems to apply outside the 24-hour time window and minimal stroke symptoms for which the treatment is currently recommended, based on results from the INSPIRES trial.

Administered within 72 hours after onset of mild ischemic stroke or high-risk transient ischemic attack (TIA), the combination of clopidogrel (Plavix) plus aspirin resulted in a decrease in any new stroke within 90 days compared with aspirin alone (7.3% vs 9.2%; HR 0.79, 95% CI 0.66-0.94).

The downside was a doubling in moderate-to-severe bleeding at 90 days (0.9% vs 0.4%; HR 2.08, 95% CI 1.07-4.04), reported Yilong Wang, MD, PhD, of Beijing Tiantan Hospital in China, and colleagues in the New England Journal of Medicine.

"The results of our trial potentially broaden the time window for the initiation of treatment, although there was more bleeding with the dual regimen than with the monotherapy," the INSPIRES authors concluded.

For their trial, Wang and colleagues enrolled people with minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5) and high-risk TIA (score of 4 or higher on the ABCD² [age, blood pressure, clinical features, duration of symptoms, and presence of diabetes] scale), which marks a step up from the NIHSS threshold of ≤3 that had been used in the POINT and CHANCE trials that established DAPT's benefit for secondary stroke prevention.

INSPIRES also expanded the pool of patients receiving DAPT by testing it within 72 hours. POINT and CHANCE had tested this therapy within 12 and 24 hours, respectively, as this early period is thought to carry the highest risk of recurrent stroke.

Based on these two older trials, the American Heart Association in 2019 updated its guidelines with a class Ia recommendation for a 21-day course of aspirin plus clopidogrel starting within 24 hours for patients with noncardioembolic ischemic stroke and NIHSS scores of 3 or less who didn't get IV thrombolytics.

With the addition of INSPIRES, there is evidence to support expanding the time window for DAPT to 72 hours, commented Anthony Kim, MD, of University of California, San Francisco.

"This timing should nevertheless be interpreted as 'as soon as possible, but within 72 hours' and still necessitates a loading dose of clopidogrel, since its omission would be akin to delaying treatment," Kim urged in his accompanying editoria.

"Overall, for every 1,000 patients with TIA or mild stroke who were treated with clopidogrel–aspirin, approximately 19 fewer strokes and 5 additional moderate-to-severe bleeding events would be expected as compared with aspirin alone, by my rough calculation," he wrote.

For now, DAPT appears to be underutilized in practice: a recent study found that from 2018 to 2021, just over 40% of stroke patients with an NIHSS score of 3 or less were prescribed DAPT after minor stroke or transient ischemic attack in a population-based registry from the University of Maryland Medical System.

INSPIRES was a double-blind 2x2 factorial trial conducted at 222 hospitals in China.

Participants were 6,100 people with mild ischemic stroke or high-risk TIA -- largely the former -- presumably caused by atherosclerotic stenosis of extracranial or intracranial artery ipsilateral to the ischemic field, or multiple infarctions with nonstenotic atherosclerotic plaque ipsilateral to the ischemic field.

Study protocol had people randomly assigned within 72 hours after symptom onset to DAPT with clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100-300 mg on day 1 and 100 mg daily on days 2 to 21) or aspirin plus placebo.

The cohort had a median age of 65 years, with just over 35% women. Three in four individuals had a NIHSS ≤3, and the remaining quarter had severity scores reach 4 or 5. Approximately 13% of patients were treated within 24 hours of stroke onset.

Subgroup analysis suggested that DAPT prevented recurrent strokes mainly in people randomized between 48 hours and 72 hours -- no earlier.

Additionally, the risk of any bleeding was higher in the clopidogrel-aspirin group (3.1% vs 2.1%, HR 1.50, 95% CI 1.09-2.06).

"This bleeding signal is a reminder that the appropriate duration of dual antiplatelet therapy to balance early benefit and bleeding risk seems to be approximately 21 days and that long-term use of clopidogrel-aspirin is not recommended, given that this approach has not proved beneficial and almost certainly increases bleeding risk," Kim noted.

Chief among the limitations of INSPIRES was a selected cohort that excluded people with presumed cardioembolic TIA or ischemic stroke, people with moderate or severe stroke, patients already on DAPT or intensive statin therapy before the trial, and those who had undergone thrombolysis or thrombectomy. Results may have limited generalizability given a study population that was predominantly Han Chinese.

Furthermore, other antiplatelet regimens were not studied in this trial.

"The incremental expansion of indications for [DAPT] that was shown in this trial is welcome. Perhaps new, more targeted antithrombotic agents on the horizon may hold promise for delivering an even more favorable balance of benefits and risks among patients with stroke," Kim wrote.

• 

  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The trial was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, the Beijing Outstanding Young Scientist Program, the Youth Beijing Scholar Program, the Beijing Talent Project–Class A: Innovation and Development, the National Ten Thousand Talent Plan-Leadership of Scientific and Technological Innovation, Sanofi, and Beijing Jialin Pharmaceuticals.

Wang disclosed institutional grants from Beijing Jialin Pharmaceuticals and Sanofi.

Kim disclosed receiving institutional research grants from the American Heart Association, NIH, and PCORI.

Primary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowGao Y, et al "Dual antiplatelet treatment up to 72 hours after ischemic stroke" N Engl J Med 2023; DOI: 10.1056/NEJMoa2309137.

Secondary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowKim AS "Extending dual antiplatelet therapy for TIA or stroke" N Engl J Med 2023; DOI: 10.1056/NEJMe2311961.

DAPT noninferior to alteplase in minor nondisabling acute ischemic stroke

So both pretty much failed at 100% recovery but your writeup failed to acknowledge that, for that lie I'd fire you all. The only goal in stroke is 100% recovery, when will you quit being a blithering idiot?

DAPT noninferior to alteplase in minor nondisabling acute ischemic stroke

Key takeaways:

• At 90 days after minor nondisabling acute ischemic stroke, there was no difference in functional outcomes between treatment with DAPT or alteplase.
• Safety outcomes were slightly better with DAPT.

In patients with minor nondisabling acute ischemic stroke, treatment with dual antiplatelet therapy was noninferior to treatment with IV alteplase, according to the results of the ARAMIS trial.

The researchers randomly assigned 760 patients (median age, 64 years; 31% women) with minor nondisabling acute ischemic stroke — defined as NIH Stroke Scale score of 5 or less, plus 1 point or less on single-item scores such as vision, language, neglect or single limb weakness, and a score of 0 in the consciousness item — to DAPT or IV alteplase. The patients, who were treated at 38 hospitals in China, underwent randomization within 4.5 hours of symptom onset and had a median NIH Stroke Scale score of 2.

At 90 days after minor nondisabling acute ischemic stroke, there was no difference in functional outcomes between treatment with DAPT or alteplase.
Data were derived from Chen HS, et al. JAMA. 2023;doi:10.1001/jama.2023.7827.

The DAPT group received clopidogrel 300 mg and aspirin 100 mg on the first day followed by clopidogrel 75 mg and aspirin 100 mg for 12 days, and then guideline-based antiplatelet therapy until 90 days. The alteplase group received IV alteplase 0.9 mg/kg up to 90 mg on the first day followed by guideline-based antiplatelet therapy starting 24 hours after the alteplase dose.

The primary endpoint was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1, at 90 days.(1 is not excellent according to survivors, you can't let your stroke medical 'professionals' use the tyranny of low expectations on you!)

At 90 days, 93.8% of patients in the DAPT group and 91.4% of those in the alteplase group had excellent functional outcome (risk difference, 2.3%; 95% CI, –1.5 to 6.2; crude RR = 1.38; 95% CI, 0.81-2.32), Hui-Sheng Chen, MD, from the department of neurology, General Hospital of Northern Theatre Command in Shenyang, China, and colleagues wrote.

The unadjusted lower limit of the 97.5% CI was –1.5%, beating the noninferiority margin of –4.5% (P for noninferiority < .001), according to the researchers.

Symptomatic intracranial hemorrhage at 90 days occurred in one patient (0.3%) from the DAPT group and in three patients (0.9%) from the alteplase group, the researchers wrote.

Various sensitivity analyses did not change the results.

“This finding, along with better safety outcomes, provides robust evidence for the effectiveness of DAPT being noninferior to intravenous alteplase in patients with minor nondisabling acute ischemic stroke,” Chen and colleagues wrote.

DAPT noninferior to alteplase in minor nondisabling acute ischemic stroke

 Well, you're not measuring 100% recovery, so you're not even doing correct research, get some retraining.

DAPT noninferior to alteplase in minor nondisabling acute ischemic stroke

Key takeaways:

• At 90 days after minor nondisabling acute ischemic stroke, there was no difference in functional outcomes between treatment with DAPT or alteplase.
• Safety outcomes were slightly better with DAPT.

In patients with minor nondisabling acute ischemic stroke, treatment with dual antiplatelet therapy was noninferior to treatment with IV alteplase, according to the results of the ARAMIS trial.

The researchers randomly assigned 760 patients (median age, 64 years; 31% women) with minor nondisabling acute ischemic stroke — defined as NIH Stroke Scale score of 5 or less, plus 1 point or less on single-item scores such as vision, language, neglect or single limb weakness, and a score of 0 in the consciousness item — to DAPT or IV alteplase. The patients, who were treated at 38 hospitals in China, underwent randomization within 4.5 hours of symptom onset and had a median NIH Stroke Scale score of 2.

At 90 days after minor nondisabling acute ischemic stroke, there was no difference in functional outcomes between treatment with DAPT or alteplase.
Data were derived from Chen HS, et al. JAMA. 2023;doi:10.1001/jama.2023.7827.

The DAPT group received clopidogrel 300 mg and aspirin 100 mg on the first day followed by clopidogrel 75 mg and aspirin 100 mg for 12 days, and then guideline-based antiplatelet therapy until 90 days. The alteplase group received IV alteplase 0.9 mg/kg up to 90 mg on the first day followed by guideline-based antiplatelet therapy starting 24 hours after the alteplase dose.

The primary endpoint was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1, at 90 days.

At 90 days, 93.8% of patients in the DAPT group and 91.4% of those in the alteplase group had excellent functional outcome (risk difference, 2.3%; 95% CI, –1.5 to 6.2; crude RR = 1.38; 95% CI, 0.81-2.32), Hui-Sheng Chen, MD, from the department of neurology, General Hospital of Northern Theatre Command in Shenyang, China, and colleagues wrote.

The unadjusted lower limit of the 97.5% CI was –1.5%, beating the noninferiority margin of –4.5% (P for noninferiority < .001), according to the researchers.

Symptomatic intracranial hemorrhage at 90 days occurred in one patient (0.3%) from the DAPT group and in three patients (0.9%) from the alteplase group, the researchers wrote.

Various sensitivity analyses did not change the results.

“This finding, along with better safety outcomes, provides robust evidence for the effectiveness 

(It's not effective is it? Not getting to 100% recovery. I hate your tyranny of low expectations!)of DAPT being noninferior to intravenous alteplase in patients with minor nondisabling acute ischemic stroke,” Chen and colleagues wrote.