Bristol Stroke Victim Finds New Hope in Revolutionary Language Therapy

 Hopefully your doctor has enough clout to find out the specifics of this therapy. They never do say what version of aphasia this treats.

Bristol Stroke Victim Finds New Hope in Revolutionary Language Therapy

In the heart of Bristol, a story of resilience and breakthrough unfurls, marking a beacon of hope for stroke survivors. It's the journey of an individual who, in the silence that followed a devastating stroke, found a way to 'make her voice heard' again. This narrative isn't just about overcoming the odds; it's a testament to the power of human innovation and the relentless pursuit of solutions that can transform lives.

A New Dawn in Stroke Rehabilitation

The innovative therapy that has begun to change the lives of stroke victims in Bristol is not just another treatment; it's a pioneering approach to rehabilitation. For many who have suffered strokes, the loss of language and communication skills is among the most challenging consequences to navigate. However, researchers in Bristol have offered a glimmer of hope through an intensive language therapy tailored specifically for stroke survivors. This therapy, grounded in years of research and development, aims to help individuals regain their ability to communicate, thereby significantly improving their quality of life.

While the specifics of the therapy remain under wraps, its core is designed to stimulate the areas of the brain responsible for language and communication. Through a combination of cutting-edge technology and personalized care plans, this therapy represents a significant leap forward in our understanding of stroke rehabilitation. The success stories emerging from Bristol are not just inspiring; they're a clarion call for the wider adoption of such therapeutic interventions.

The Science Behind the Breakthrough

At the heart of this revolutionary therapy is a profound understanding of the brain's ability to heal and adapt. Known as neuroplasticity, this concept has been the driving force behind the development of the therapy, enabling patients to rewire their brains and reclaim their voices. The approach is holistic, combining elements of speech therapy, cognitive exercises, and sometimes, technological aids to facilitate communication.

The significance of this development cannot be overstated, especially when considering the broader landscape of stroke treatment and rehabilitation. For instance, Milvexian, a novel therapy developed by Bristol-Myers Squibb, is currently making waves in the treatment of acute ischemic stroke. Although it targets the physical manifestations of strokes, such as thrombosis, the complementary nature of language therapy underscores the importance of addressing both the physical and cognitive repercussions of strokes.

Looking to the Future

The journey of the Bristol stroke victim is far from an isolated case. It symbolizes a broader movement towards innovative, patient-centered care in the realm of stroke rehabilitation. As this therapy continues to gain traction, it paves the way for further research and the potential for similar therapies to emerge, offering hope to millions of stroke survivors worldwide.

The narrative unfolding in Bristol is a powerful reminder of the resilience of the human spirit and the boundless potential for medical innovation to change lives. As we look towards the future, it's clear that the interplay between emerging therapies like Milvexian and groundbreaking rehabilitative treatments will play a crucial role in shaping the landscape of stroke recovery.

For stroke survivors, their families, and the medical community, the developments in Bristol represent more than just a new therapy; they signify a new horizon of possibilities, where the ability to speak and communicate can be reclaimed, and the journey of recovery is filled with hope.

Oral Factor XIa Inhibitor Disappoints for Secondary Stroke Prevention

So EXACTLY what is your doctor doing to guarantee no further strokes?

Oral Factor XIa Inhibitor Disappoints for Secondary Stroke Prevention

Milvexian did not reduce strokes or covert brain infarcts in AXIOMATIC-SSP

by Sophie Putka, Enterprise & Investigative Writer, MedPage Today December 28, 2023

Factor XIa inhibitor milvexian did not provide meaningful secondary prevention over dual antiplatelet therapy for stroke survivors, the phase II trial AXIOMATIC-SSP found.

In patients with recent ischemic stroke or transient ischemic attack (TIA), randomization to any one of five doses of milvexian did not significantly reduce the combined incidence of ischemic stroke or covert brain infarct on MRI at 90 days (range from 15.3% for 200 mg twice daily to 16.7% for 25 mg once daily) compared with placebo (16.8%), reported Mukul Sharma, MD, of McMaster University in Hamilton, Ontario, and co-authors.

No significant dose-response was observed for the primary efficacy outcome, nor was one observed for major bleeding, the investigators reported in Lancet Neurology.

Paradoxically, a prior analysis showed that milvexian numerically lowered the risk of clinical ischemic strokes, not counting covert brain infarctions, in the four lower dose groups but not in the highest dose group.

Milvexian's promise as an antithrombotic rests on evidence that people with factor XI deficiency have lower rates of ischemic stroke than the general population and infrequent spontaneous bleeding, the authors noted. Milvexian is an oral inhibitor of activated factor XIa and is rapidly absorbed after oral administration, with a half-life of approximately 12 hours. The hope is that it would carry a lower risk of complications compared with available anticoagulants.

Previous phase II trials had supported milvexian as an effective anticoagulant with a good safety profile. In another phase II trial, milvexian showed a dose-response relationship with prevention of venous thromboembolism after elective knee arthroplasty alongside low bleeding.

However, in AXIOMATIC-SSP, the highest dose of milvexian was associated with renal adverse events and subsequent study discontinuation, Pooja Khatri, MD, of the University of Cincinnati, pointed out in an accompanying editorial.

"As expected, most of the primary outcome events within the trial were covert brain infarcts and, disappointingly, the results showed that milvexian had no dose-response effect," she wrote.

Another dose-finding study, PACIFIC-Stroke, showed similarly disappointing efficacy results for another factor XIa inhibitor, asundexian, over placebo.

"Together, the results of these trials suggest that factor XI and factor XIa inhibitors might not prevent noncardioembolic stroke. This possibility becomes more likely if covert brain infarcts are considered as part of the same biological spectrum as symptomatic cerebral ischaemia, but smaller or in less eloquent areas of the brain," Khatri suggested.

Hints of efficacy in these trials may have been "spurious," she noted, though phase III trials may "tip the balance towards benefiting patients with non-cardioembolic cerebral ischaemia."

Milvexian is now under investigation in the phase III LIBREXIA-STROKE trial that is testing the 25-mg twice-daily dose against placebo in a targeted population of 15,000 stroke or TIA patients.

AXIOMATIC-SSP was conducted from 2019 to 2021 in 367 hospitals in 27 countries. Enrollees were adults ages 40 and older, with acute ischemic stroke or high-risk TIA, seen within 48 hours of symptom onset. Participants had imaging evidence of interior or exterior atherosclerosis in a feeding artery and a premorbid modified Rankin scale score of 3 or lower.

Sharma and colleagues ultimately had 2,366 individuals in the study cohort. Their median age was 71 years, 36% were women, and 80% were white.

Patients were randomized to one of five doses of milvexian, or placebo, for 90 days. All participants also received clopidogrel (Plavix) 75 mg daily for the first 21 days and aspirin 100 mg daily for 90 days.

An MRI scan was performed at baseline and at 90 days.

The researchers were limited by a study completion rate of 75% due to adverse events and COVID-19 pandemic-related difficulties. Another limitation was the low representation of women in the trial population.

Sharma's group also acknowledged the trial's reliance on covert brain infarcts as a surrogate for clinical ischemic stroke in the composite primary outcome, as these infarcts contributed most of the primary outcome events. The validity of this surrogate marker is still unclear, the authors wrote.

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  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 trial came from Bristol Myers Squibb and Janssen.

Sharma disclosed relationships with Janssen, HLS Therapeutics, Bayer, and the Canadian Stroke Consortium.

Study co-authors had multiple relationships with industry, including several as employees of Bristol Myers Squibb.

Khatri disclosed relationships with Bayer, Cerenovus, the National Institutes of Health, UpToDate, Basking Biosciences, Lumosa, and Shionogi.

Primary Source

Lancet Neurology

Source Reference: Sharma M, et al "Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial" Lancet Neurol. 2023; DOI: 10.1016/S1474-4422(23)00403-9.

Secondary Source

Lancet Neurology

Source Reference: Khatri P, "Anticoagulants to prevent recurrent non-cardioembolic stroke" Lancet Neurol. 2023; DOI: 10.1016/S1474-4422(23)00464-7.

Milvexian appears safe for secondary prevention of stroke

FYI.  Ask your doctor is this is better than warfarin, aspirin or Eliquis, Pradaxa, Savaysa, Xarelto. And what the reversal agent is if needed

Milvexian appears safe for secondary prevention of stroke

In the AXIOMATIC-SSP trial, milvexian, a novel factor XIa inhibitor, was protective against ischemic stroke with no increased risk for intracranial hemorrhage compared with placebo in patients requiring secondary prevention.

“Milvexian ... has the potential to reduce stroke without an increase in intracranial hemorrhage,” Mukul Sharma, MD, MSc, deputy director of clinical affairs and health policy, director of regional stroke program in the Canadian Stroke Network and assistant professor of medicine in the department of neurology at University of Ottawa in Ontario, Canada, said during a press conference at the European Society of Cardiology Congress. “If we think about the type of hemorrhages that occur in the setting of antithrombotics, the one type that is most comparable to ischemic stroke is hemorrhagic ... Compared to placebo, all doses of milvexian had a lower risk of having a symptomatic ischemic stroke, apart from the 200 mg [twice daily] dose arm. We did not see a dose relationship between the dose of milvexian and intercranial hemorrhage.”

Source: Adobe Stock

Milvexian (Bristol Myers Squibb/Janssen) was previously tested in the phase 2 AXIOMATIC-TKR trial, published in The New England Journal of Medicine, for the prevention of venous thromboembolism after knee arthroplasty compared with enoxaparin.

As Healio previously reported, oral milvexian effectively prevented venous thromboembolism and was associated with a low rate of bleeding following knee arthroplasty.

For the phase 2 AXIOMATIC-SSP trial, researchers tested the dose-response relationship of milvexian for the secondary prevention of stroke, with the primary outcome being symptomatic ischemic stroke and covert brain infarction. Covert infarcts were identified by comparing baseline and 90-day MRIs.

Sharma and colleagues enrolled 2,295 patients with acute stroke or transient ischemic attack who, within 48 hours of symptom onset and MRI, were randomly assigned to placebo, once-daily milvexian 25 mg or twice-daily milvexian 25 mg, 50 mg, 100 mg or 200 mg.

All participants received the same background therapy of 21-day dual antiplatelet therapy (clopidogrel 75 mg and aspirin 100 mg) followed by aspirin monotherapy out to 90 days.

For twice-daily milvexian 25 mg, 50 mg and 100 mg, researchers observed an approximately 30% relative risk reduction for symptomatic ischemic stroke compared with placebo; however, no dose response was observed:

• 25 mg twice daily (RR = 0.69; 95% CI, 0.36-1.3);
• 50 mg twice daily (RR = 0.72; 95% CI, 0.39-1.33); and
• 100 mg twice daily (RR = 0.65; 95% CI, 0.33-1.25).

The risk reduction was lesser for patients assigned to milvexian 25 mg once daily compared with placebo (RR = 0.83; 95% CI, 0.46-1.49) and researchers reported an increased risk for stroke within the 200 mg twice daily group (RR = 1.4; 95% CI, 0.87-2.25).

Sharma and colleagues observed no increase in fatal bleeding or covert brain infarction associated with milvexian compared with placebo.

“The primary endpoint [of AXIOMATIC-SSP trial] did not achieve significance because covert infarcts weren’t affected by factor XI inhibition,” Sharma said during the press conference. “However, the important endpoint of symptomatic ischemic stroke was affected. Based on this signal of efficacy for symptomatic ischemic stroke with a [safe] fatal bleeding profile, milvexian will be studied further in phase 3 trials.”