Expanding the Window: New Trial Finds Clot-Busting Drug Helps Stroke Patients Up to 24 Hours After Onset

 For decades, the clock has been the enemy in stroke care. Every minute without treatment means more brain cells lost — and for patients who arrive at the hospital more than four and a half hours after their symptoms began, treatment options have been frustratingly limited. But a new clinical trial is challenging that boundary in a meaningful way.

What the OPTION Trial Found

Presented at the International Stroke Conference (ISC) 2026 in New Orleans, the OPTION trial tested whether intravenous tenecteplase — a clot-dissolving medication — could help patients with acute ischemic strokes caused by non-large-vessel occlusions (non-LVOs) when given between 4.5 and 24 hours after symptom onset.

The results were striking. Patients who received tenecteplase were significantly more likely to achieve an excellent functional outcome at 90 days — defined as a modified Rankin Scale score of 0 or 1 (meaning little to no disability) — compared to those who received standard care alone: 43.6% vs. 34.2%.

That's a meaningful difference in real human terms: more patients walking, talking, and living independently three months after their stroke.

Who Was in the Trial?

The trial enrolled 566 patients across 48 centers in China. Participants were adults with disabling strokes (measured by NIHSS scores), no large-vessel occlusion, and evidence of salvageable brain tissue on CT perfusion imaging. Crucially, none of them were candidates for endovascular thrombectomy — the gold-standard mechanical clot removal procedure.

The median time from last known well to treatment was 12 hours — well beyond the traditional thrombolysis window.

What About the Risks?

No treatment comes without tradeoffs. All cases of symptomatic intracranial hemorrhage (bleeding in the brain) occurred in the tenecteplase group — 2.8% versus 0% in the control arm. That's a statistically significant and clinically important difference.

However, there were no significant differences in overall mortality (5.0% vs. 3.2%) or serious systemic bleeding between the two groups at 90 days. Leading experts at ISC noted that the degree of functional benefit observed in OPTION appears to justify the relatively low rate of bleeding complications — especially given the lack of other effective options for these patients in the late time window.

The investigators did flag one important caution: two of the bleeding cases occurred in patients who had CT hypodensities larger than the imaging-defined core. Careful review of non-contrast CT scans is advisable before treating patients in this late window.

Why This Matters

More than half of all acute ischemic strokes are caused by non-LVOs. Until now, thrombolysis had only been proven beneficial within the first 4.5 hours for this group — leaving a significant population without effective late-window options.

This trial extends the evidence base considerably. As ISC Vice Chair Dr. Bijoy Menon of the University of Calgary noted, the results are "clearly positive" and represent "one more step in our effort to actually change guidelines and practice."

The Caveats

Experts were quick to acknowledge an important limitation: the OPTION trial enrolled only patients from China. While the biology of stroke is universal, factors including genetics, comorbidities, diet, and healthcare infrastructure can influence both outcomes and risk profiles. Researchers are calling for additional trials in more diverse global populations before these findings can be applied broadly with confidence.

What Comes Next

The OPTION trial findings were published simultaneously in JAMA, lending them significant weight in the medical community. If confirmed in broader populations, this research could reshape how physicians approach stroke care in the late window — offering a lifeline to patients who currently have few options once the traditional treatment clock runs out.

For now, the message is cautiously optimistic: when endovascular treatment isn't available and the right patient is identified, tenecteplase administered up to 24 hours after stroke onset may make a meaningful difference.

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Based on findings presented at the International Stroke Conference 2026 and published in JAMA, February 2026.

2026 AHA/ASA Guidelines Expand Stroke Treatment Options

The American Heart Association/American Stroke Association (AHA/ASA) has released its most comprehensive update to acute ischemic stroke management guidelines since 2018 — and the changes are significant. From expanded eligibility for thrombolysis and mechanical thrombectomy to the first-ever guidance on pediatric stroke, this overhaul reflects years of accumulated clinical trial data and is already reshaping how stroke care is delivered.

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Why These Guidelines Matter

Seven years have passed since the last full guideline. In that time, a wave of landmark stroke trials produced results that "changed practice and should change practice more," according to Dr. Shyam Prabhakaran of the University of Chicago Medicine and chair of the writing group. The new guideline, published in Stroke and presented at the International Stroke Conference in New Orleans, aims to close that gap — and the AHA has committed to more frequent, real-time updates going forward.

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Mobile Stroke Units: A New Class 1 Recommendation

One of the most headline-worthy additions is a Class 1 recommendation in support of mobile stroke units (MSUs) — specialized ambulances equipped with CT scanners and trained teams capable of administering IV thrombolysis in the field. Supported by trials including B_PROUD and BEST-MSU, MSUs have demonstrated measurable improvements in functional outcomes for patients with suspected acute ischemic stroke.

The challenge? Adoption in the United States remains limited due to staffing constraints and a lack of reimbursement pathways. The hope is that this guideline nudges policymakers toward broader financial support.

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Thrombolysis: Expanded Windows and a New First-Line Option

Tenecteplase Reaches Class 1 Status

Perhaps the most practice-changing update in thrombolysis is the elevation of tenecteplase (0.25 mg/kg) to a Class 1 recommendation alongside alteplase (0.9 mg/kg) for patients presenting within 4.5 hours of stroke onset. Multiple trials established tenecteplase's non-inferiority, and its practical advantages are compelling: it's administered as a single injection rather than a one-hour infusion, simplifying workflows and facilitating rapid interhospital transfer.

Extended Treatment Windows

The guidelines also push the boundaries of when thrombolysis can be considered:

• 4.5 to 9 hours after onset (or wake-up stroke): Class 2a recommendation when advanced imaging confirms salvageable brain tissue (supported by the EXTEND trial).
• 4.5 to 24 hours in select patients with large-vessel occlusions (LVOs) who cannot undergo thrombectomy: Class 2b recommendation, supported by the HOPE and TRACE-III trials (despite the TIMELESS trial's neutral findings for tenecteplase in this window).

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Mechanical Thrombectomy: More Patients, More Conditions

Large-Core Strokes and Extended Windows

Thrombectomy eligibility has expanded substantially. A new Class 1 recommendation supports thrombectomy for patients with anterior circulation LVOs presenting 6 to 24 hours after onset who are under 80, have an NIHSS score ≥ 6, and show an ASPECTS score of 3 to 5 without significant mass effect — based on the SELECT2 and ANGEL-ASPECT trials.

Posterior Circulation

Evidence from the ATTENTION and BAOCHE trials now supports thrombectomy for basilar artery occlusion (Class 1): patients with an NIHSS ≥ 10 and mild ischemic damage presenting within 24 hours should be considered for the procedure to improve outcomes and reduce mortality.

Where Evidence Is Still Limited

The guidelines are more cautious about medium- and small-vessel occlusions (distal vessels), where current device technology has not yet demonstrated consistent efficacy. More trials are anticipated as technologies improve.

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Medical Management Updates

Blood Glucose Control

A Class III recommendation advises against using IV insulin to target blood glucose of 80–130 mg/dL in hospitalized stroke patients with hyperglycemia. The approach hasn't shown functional benefit and raises the risk of severe hypoglycemia.

Blood Pressure Targets After Reperfusion

Two important Class III recommendations address blood pressure management:

1. After IV thrombolysis for mild-to-moderate stroke, do not lower systolic BP below 140 mmHg (vs. the previous 180 mmHg target) — intensive reduction showed no functional benefit.
2. After successful endovascular thrombectomy for anterior circulation LVO, avoid BP goals below 140 mmHg for the first 72 hours post-recanalization, as supported by ENCHANTED2/MT and OPTIMAL-BP — this approach may cause harm.

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Pediatric Stroke: A First Step

For the first time, the guidelines include dedicated guidance on pediatric stroke — addressing diagnosis, and considering thrombolysis and endovascular thrombectomy in younger patients. The evidence base here is still developing, but clinicians now have a starting framework. Further trials in this underserved population are a clear priority.

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What's on the Horizon?

Several knowledge gaps remain ripe for future research:

• Distal vessel thrombectomy as device technology matures
• Advanced imaging to safely guide thrombolysis in extended windows, particularly in low-resource settings
• Neuroprotective agents as adjunctive therapy in the modern reperfusion era — a category that may warrant revisiting given improved patient selection

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The Bottom Line

The 2026 AHA/ASA guidelines represent a meaningful leap forward in stroke care, driven by a decade of robust clinical trial data. The expansion of treatment eligibility — in terms of both time windows and patient profiles — offers clinicians more tools and more opportunities to improve outcomes. As the AHA transitions to real-time guideline updates, clinicians can expect the evidence to keep moving. The key question now is whether health systems, payers, and policymakers will keep pace.

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Source: AHA/ASA Early Management of Acute Ischemic Stroke Guideline, published in Stroke (January 2026). Presented at the International Stroke Conference, New Orleans, LA.

Loberamisal Scores a Rare Win for Stroke Neuroprotection

February 12, 2026  |  International Stroke Conference, New Orleans, LA

A novel drug called loberamisal has delivered a rare breakthrough in stroke neuroprotection, showing significant improvement in patient outcomes in the phase III LAIS trial — the first large neuroprotectant trial to produce positive results.

What the Trial Found

Nearly 1,000 patients with acute ischemic stroke were randomized to receive loberamisal or placebo within 48 hours of symptom onset. At 90 days, 69.7% of patients on loberamisal achieved an excellent functional outcome (modified Rankin Scale score 0–1), compared to 56.4% on placebo. The drug also reduced rates of depression and anxiety at 90 days, with no significant safety concerns.

Why It's Different

Unlike previous neuroprotectants that failed in clinical trials, loberamisal works on two targets — inhibiting PSD-95 and acting on the α2-GABA receptor — reducing both brain injury and mood disorders in stroke survivors. It was also given much later (up to 48 hours) than prior agents, reaching patients who had missed the window for reperfusion therapy.

Why It Matters

Most stroke patients never receive acute treatments like thrombolysis or thrombectomy — they arrive too late or are ineligible. Loberamisal's wide treatment window could offer something meaningful to this large, underserved population. Experts are calling for larger global trials to confirm the results across diverse populations.

"Having something to offer all patients that come in within 48 hours would be a game changer." — Stroke neurologist, Yale School of Medicine

Source: International Stroke Conference 2026; LAIS Trial. This article is for informational purposes only and does not constitute medical advice.

🫀 VESALIUS-CV: Evolocumab Protects the Heart Before Trouble Begins

🌟 A New Frontier in Prevention

A quiet revolution in cardiology took shape at the AHA 2025 Scientific Sessions and in the pages of the New England Journal of Medicine.

The VESALIUS-CV trial is the first to show that a PCSK9 inhibitor — evolocumab (Repatha; Amgen) — can prevent first major cardiovascular events in people who have never had a heart attack or stroke.

It signals a shift from treating damage to preventing disease altogether — a milestone for lipid management.

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🧪 Inside the VESALIUS-CV Trial

12,257 patients, all at high cardiovascular risk but with no prior MI or stroke, were randomized to evolocumab 140 mg every 2 weeks or placebo, on top of statin therapy.
After 4.6 years of follow-up, the results spoke clearly:

💥 Major Outcomes

• LDL-C reduction: 55%, to ~45 mg/dL

• MACE reduction: 25% (HR 0.75; 95% CI 0.65–0.86)

• Expanded endpoint (including revascularization): 19% reduction (HR 0.81)

• Safety: No new concerns observed

These findings validate that pushing LDL even lower — near 40 mg/dL — can save lives long before a first event.

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🔍 How It Differs from Earlier Trials

Earlier studies such as FOURIER and ODYSSEY Outcomes established PCSK9 inhibitors for secondary preventionafter MI or stroke.
VESALIUS-CV, in contrast, entered unexplored territory — patients with atherosclerosis or high-risk diabetes but no prior events.

It featured:

• Higher baseline LDL (~122 mg/dL)

• Longer follow-up (4.6 years vs 2.2)

• Greater relative and absolute benefit

In essence, it moves PCSK9 therapy upstream, redefining prevention itself.

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💡 Clinical Takeaway

For clinicians, this means one thing: don’t wait for the first plaque to rupture.
Identify the silent high-risk — those with subclinical CAD, diabetes, PAD, or elevated apoB — and treat aggressively early.

With the FDA’s expanded indication for evolocumab in primary prevention, the data now give physicians stronger footing to act before the first heart attack.

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🩺 Key Points for Busy Clinicians

✅ First PCSK9 trial to prove benefit in event-free, high-risk patients
✅ Evolocumab cut MACE by 25%, LDL to ~45 mg/dL, with excellent safety
✅ Longer duration and earlier intervention than prior PCSK9 studies
✅ Supports LDL targets near 40 mg/dL in high-risk, primary-prevention cohorts

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✨ The Takeaway:
VESALIUS-CV brings preventive cardiology full circle — proving that aggressive LDL lowering saves lives even before the first event.
The era of “treat early, prevent completely” has begun.

OPTIMA-AF: One-Month Dual Therapy After PCI in Atrial Fibrillation Matches One-Year Regimen, With Less Bleeding

Results from the OPTIMA-AF trial, presented by Yohei Sotomi, MD, PhD of the Osaka University Graduate School of Medicine, Japan, at the American Heart Association (AHA) 2025 Scientific Sessions and simultaneously published in the New England Journal of Medicine, suggest that one month of dual antithrombotic therapy after PCI may be all that’s needed for many patients with atrial fibrillation (AF) and coronary artery disease (CAD).

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Shorter Therapy, Same Efficacy, Less Bleeding

The study enrolled 1,088 patients (mean age 75; 79% men) with AF and stable or unstable angina or silent myocardial ischemia, but excluded those with acute myocardial infarction (STEMI or NSTEMI). All participants underwent imaging-guided PCI with everolimus-eluting stents (Xience, Abbott).

Patients were randomized to either:

• Short-duration therapy: 1 month of a direct oral anticoagulant (DOAC) plus a P2Y12 inhibitor (clopidogrel or prasugrel), followed by DOAC monotherapy for the remaining 11 months.

• Long-duration therapy: The same DOAC plus P2Y12 inhibitor continued for the entire 12 months.

• Aspirin use was optional but limited to the first month post-PCI.

At 1 year, death or thromboembolic events occurred in 5.4% of the short-duration group versus 4.5% of the long-duration group (P = 0.002 for noninferiority). Major or clinically relevant nonmajor bleeding was cut nearly in halfwith shorter therapy (4.8% vs 9.5%; P = 0.004).

“Patients with AF who receive a stent may only need one month of dual antithrombotic therapy instead of one year,” Sotomi said, highlighting the potential to reduce bleeding complications without compromising protection against ischemic events.

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Implications for Clinical Practice

The results support a de-escalation strategy that balances ischemic protection with bleeding risk, aligning with evolving guidelines that favor early discontinuation of antiplatelet therapy in select patients after PCI.

However, experts urged caution before adopting this approach universally. The study population consisted solely of East Asian patients, who may have different bleeding and thrombotic risk profiles than Western populations. Larger, diverse global studies are needed to confirm safety and efficacy across broader patient groups.

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Key Takeaway

In patients with atrial fibrillation undergoing PCI for stable or unstable CAD, one month of DOAC plus P2Y12 inhibitor, followed by DOAC alone, provides similar ischemic protection and significantly less bleeding than continuing dual therapy for a full year. If validated in more diverse populations, this strategy could redefine post-PCI antithrombotic management—offering simpler, safer, and more individualized care.

(Source: AHA 2025 Scientific Sessions; NEJM 2025)

CRISPR Therapy CTX310 Shows Promise for Hard-to-Treat Dyslipidemia

A first-in-human CRISPR-Cas9 gene-editing therapy, CTX310, targeting angiopoietin-like protein 3 (ANGPTL3), has shown encouraging results in patients with refractory dyslipidemia, according to a phase I study presented at the AHA 2025 Scientific Sessions and published in the New England Journal of Medicine.

Given as a one-time IV infusion, CTX310 produced mean reductions of 48.9% in LDL cholesterol and 55.2% in triglycerides at the highest dose over 60 days. Other lipids—including apolipoprotein B and non-HDL cholesterol—also declined significantly. Importantly, no dose-limiting toxicities or serious treatment-related adverse events were reported.

The therapy uses lipid nanoparticles to deliver CRISPR components to the liver, inducing a loss-of-function mutation in ANGPTL3—a mechanism inspired by people with natural mutations who have lifelong low cholesterol and reduced ASCVD risk.

Experts called the results “a new frontier” in lipid management but urged caution and long-term safety follow-up, especially for potential off-target or liver effects. If proven durable and safe, CTX310 could one day offer a “one-and-done” alternative to chronic statins, PCSK9 inhibitors, or ANGPTL3 antibodies like evinacumab.

Key Takeaway:
Early data show that CTX310 can profoundly lower LDL-C and triglycerides after a single dose, potentially transforming lipid therapy—pending confirmation of long-term safety and efficacy.

Aspirin vs. Anticoagulation After AF Ablation: No Difference, Says OCEAN Trial

The OCEAN trial, presented at the American Heart Association 2025 Scientific Sessions, found no significant difference in stroke, systemic embolism, or MRI-detected cerebral infarctions between aspirinand rivaroxaban (Xarelto) after successful atrial fibrillation (AF) ablation.

Over a 36-month follow-up, both groups showed remarkably low event rates, with primary outcomes occurring in 0.8% (rivaroxaban) vs 1.4% (aspirin)—a nonsignificant difference. Major bleeding was rare but slightly higher in the anticoagulation arm (1.6% vs 0.6%).

Experts noted that these results echo findings from the ALONE-AF trial, suggesting that in low-risk post-ablationpatients (CHA₂DS₂-VASc ≤3, no recent stroke), it may be reasonable to discontinue oral anticoagulation under close supervision.

While current AHA/ACC/HRS guidelines still recommend continued anticoagulation post-ablation, OCEAN provides important real-world evidence to inform shared decision-making between physicians and patients.

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Key Takeaway:
For stable, low-to-moderate-risk AF patients one year post-ablation, aspirin and rivaroxaban appear equally effective in preventing stroke and embolic events—with very low absolute risk. Clinical judgment and individualized discussionremain essential before stopping oral anticoagulation.

Hot Topics at AHA Meeting 2025

 Here is a list of all the hot topics at AHA 2025 based on the latest information:

• 27 late-breaking science (LBS) presentations over seven sessions

• First-in-human CRISPR-Cas9 gene-editing therapy targeting ANGPTL3 (lipid metabolism)

• POLY-HF trial testing polypill strategy in heart failure patients

• OCEAN trial on optimal antithrombotic strategy post-AF ablation (rivaroxaban vs aspirin)

• META-AF trial examining metformin after AF ablation

• DARE-AF trial on SGLT2 inhibitors post-AF ablation

• DECAF trial testing whether quitting coffee reduces recurrent AF risk

• RECOVERY trial comparing early surgery vs conservative management in asymptomatic severe aortic stenosis

• FAVOR IV-QVAS trial investigating FFR-guided CABG outcomes in valve surgery patients with CAD

• CORALreef Lipids study of oral PCSK9 inhibitor enlicitide decanoate

• SSTT study on oral potassium chloride supplementation for blood pressure control in hypertension

• BETTER-BP, GoFresh, and Healthy Family Program trials on dietary and lifestyle interventions for blood pressure reduction

• CELEBRATE trial on zalunfiban pretreatment in STEMI patients undergoing PCI

• CorCMR trial on noninvasive endotyping in angina without obstructive coronary disease

• CAVIAR trial assessing PCSK9 inhibitor for cardiac allograft vasculopathy inhibition

• SURPASS-CVOT trial comparing tirzepatide vs dulaglutide on heart failure outcomes in type 2 diabetes with cardiovascular disease

• Five late-breaking basic science sessions covering genetics, coagulation, lipid research, bioartificial organs, pregnancy-related hypertensive disorders, and artificial intelligence

• Short, punchy "TED talk"-style special sessions focusing on key takeaways from complex science accessible to general cardiology audience

• Hypertrophic Cardiomyopathy Medical Society program running all day Saturday

• Plenary sessions hosted by TCT including intravascular imaging, hemodynamic support, coronary physiology, renal denervation

• Resuscitation Science Symposium running November 8 and 9

• Nobel Laureate Ardem Patapoutian lecture on mechanical sensing receptors

• Paul Dudley White lecture by Susan R. Davis on sex hormones in cardiometabolic health

These topics highlight a broad and cutting-edge agenda addressing clinical trials, basic science, technology innovations, and practical cardiology discussions at AHA 2025.

Zalunfiban’s Breakthrough in STEMI: Positive Top-Line Results from the CELEBRATE Prehospital Trial

Introduction

Reperfusion delay remains a central challenge in ST-elevation myocardial infarction (STEMI) care. Despite the advances in percutaneous coronary intervention (PCI), the time between symptom onset and coronary artery opening often dictates infarct size, microvascular injury, and clinical outcomes. To that end, the idea of initiating potent antiplatelet therapy in the prehospital setting has long been attractive, but prior strategies (especially with oral agents) have fallen short.

The CELEBRATE trial now offers a compelling proof-of-concept: administration of the novel glycoprotein IIb/IIIa inhibitor zalunfiban (aka Disaggpro) by emergency medical services (EMS) before hospital arrival has reportedly met its primary safety and efficacy endpoints. Top-line results were recently released ahead of their formal presentation at the American Heart Association 2025 meeting. (tctmd.com)

Here, we review the trial design, mechanistic rationale, implications, caveats, and future directions for this potentially practice-changing approach.

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Mechanism & Pharmacology of Zalunfiban (RUC-4 / Disaggpro)

Rationale for GPIIb/IIIa Inhibition Prehospital

• Platelet aggregation via the glycoprotein IIb/IIIa (αIIbβ3) receptor is a final common pathway in thrombus formation. In STEMI, where an occlusive thrombus is the culprit, early blockade of this pathway has strong mechanistic appeal.

• Prior trials of upstream oral P2Y₁₂ inhibitors (e.g., clopidogrel, prasugrel, ticagrelor) in the prehospital or early phase failed to show robust benefits in terms of early vessel patency, in part because the onset of action is delayed and absorption may be unpredictable in shock states. (PubMed)

• Traditional intravenous GPIIb/IIIa inhibitors (e.g., abciximab, tirofiban) have been used in-hospital or during transport, but their bleeding risk, duration of effect, and logistical challenges limit widespread adoption, especially in out-of-hospital settings. (PMC)

Zalunfiban is designed to overcome these limitations:

• It is a small-molecule, non-activating GPIIb/IIIa antagonist, amenable to subcutaneous administration, intended for rapid onset of platelet inhibition at the point of first medical contact. (PubMed)

• The onset is rapid (within 5–15 minutes), and the duration is short (effects wane over ~1–2 hours)—a profile that may enhance safety, particularly if urgent surgery becomes necessary. (CeleCor Therapeutics)

• In early-phase studies, doses of 0.110–0.130 mg/kg achieved ≥77% platelet inhibition within 15 minutes in the majority of STEMI patients. (CeleCor Therapeutics)

• In a post hoc angiographic analysis from a phase IIa cohort, higher doses of zalunfiban administered just before angiography correlated with improved TIMI flow, myocardial perfusion grade, and lower thrombus burden. (PMC)

Thus, zalunfiban may bridge the time between symptom onset and mechanical reperfusion by initiating potent platelet inhibition early, improving microvascular and macrovascular reperfusion, and potentially reducing infarct extent and downstream complications.

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Design of the CELEBRATE Trial

Overview

The CELEBRATE trial is a phase III, randomized, double-blind, placebo-controlled, multinational trial evaluating prehospital administration of zalunfiban in STEMI patients destined for primary PCI. (PubMed)

Key design features:

• Inclusion criteria: patients presenting with chest pain < 4 hours, ECG evidence of STEMI. (tctmd.com)

• Randomization in a 1:1:1 ratio to zalunfiban 0.110 mg/kg, zalunfiban 0.130 mg/kg, or placebo, administered by EMS prior to hospital arrival. (tctmd.com)

• The primary efficacy endpoint is a ranked 7-point clinical outcome scale at 30 days, capturing events from death to adverse biomarker elevation:

  1. Death

  2. Stroke

  3. Recurrent MI

  4. Acute stent thrombosis

  5. New-onset or rehospitalized heart failure

  6. MI with hs-troponin ≥ 10× upper limit of normal (ULN)

  7. None of the above (CeleCor Therapeutics)

• The primary safety endpoint is severe or life-threatening bleeding (GUSTO criteria) at 30 days. (tctmd.com)

• Enrollment target was ~2,499 patients, with modified enrollment completed by Q2–Q3 2025 and unblinding planned soon thereafter. (CeleCor Therapeutics)

• Regulatory alignment: the FDA accepted the 7-point clinical scale as a primary endpoint that could potentially support a novel drug application (NDA) if a statistically significant effect is demonstrated. (CeleCor Therapeutics)

• In the U.S., the trial is conducted under exception from informed consent (EFIC) guidelines due to the time-sensitive nature of STEMI and patient incapacity to provide consent in emergent settings. (CeleCor Therapeutics)

Thus, CELEBRATE is purposeful in marrying a pragmatic trial design (prehospital delivery by EMS) with a clinically relevant composite endpoint.

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Top-Line Results & Their Interpretation

Based on the recent news release, the trial “has met its primary safety and efficacy endpoints.” (tctmd.com)

What we do know:

• The primary endpoints (both efficacy and safety) were achieved. (tctmd.com)

• Full detailed data (effect sizes, subgroup analyses, bleeding rates, absolute event rates) have not yet been disclosed; these will be presented at the upcoming AHA Scientific Sessions in November 2025. (tctmd.com)

• The timing is consistent with prior planning: unblinding and data release in Q3 2025. (CeleCor Therapeutics)

• The press release underscores that both primary safety (i.e. severe or life-threatening bleeding) and primary efficacy were met, suggesting no unacceptable hemorrhagic risk burden. (tctmd.com)

What we don’t yet know (and must await):

• Absolute and relative event rates (e.g., reduction in mortality, MI, stent thrombosis)

• Bleeding event breakdown by dose, access site, or subgroup

• Impact on infarct size, microvascular injury, left ventricular function, or imaging endpoints

• Subgroup effects (e.g., patients with long transport times, renal dysfunction, older age)

• Safety in patients requiring surgical intervention

• Comparisons across the two zalunfiban doses

• Long-term outcomes beyond 30 days

Thus, while the topline statement is encouraging, rigorous peer-reviewed publication and detailed scrutiny will be necessary before integrating zalunfiban into guidelines or clinical practice.

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Potential Clinical Implications & Challenges

Opportunities

1. Time-to-reperfusion gains
   Administering a potent antiplatelet agent in the ambulance could shift the time–disease curve substantially, especially in settings with prolonged transport times or where in-hospital delays are common.

2. Microvascular and infarct protection
   Early platelet inhibition might reduce distal embolization, microvascular obstruction, and reduce infarct size beyond what mechanical reperfusion alone can achieve.

3. Bleeding risk balance
   The short half-life of zalunfiban (1–2 hours) may afford a better safety margin compared to prolonged-acting oral agents, especially if urgent surgery is needed. (JEMS)

4. Broad EMS deployment
   Because the drug is administered subcutaneously and does not require intravenous access or infusion pumps, it may be more deployable in diverse EMS systems (urban, rural, resource-limited). (JEMS)

5. Regulatory path
   The agreement that a positive CELEBRATE trial alone could support an NDA is a favorable regulatory design. (CeleCor Therapeutics)

Challenges & Caveats

• Operational logistics
  Training EMS staff, dose-weight calculation in the field, kit supply, and maintaining blinding are nontrivial in emergency settings.

• Bleeding risk & patient selection
  Identifying patients at high bleeding risk or contraindications in the field is challenging.

• False activations / over-treatment
  In patients without true STEMI (e.g., ECG mimic, non–coronary chest pain), exposing them to potent platelet inhibition has inherent risk.

• Surgical crossover
  Patients who require urgent coronary artery bypass grafting may pose management dilemmas if high platelet inhibition is present.

• Cost / reimbursement
  The cost of the drug, EMS infrastructure, and operational overhead must justify incremental benefit.

• Generality & external validity
  The trial will need to demonstrate benefit across geographic regions, EMS systems, and varying patient populations to drive guideline adoption.

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Future Directions & Unanswered Questions

1. Peer-reviewed publication and independent review
   The full dataset, methodology, and subgroup analyses must undergo rigorous peer review before practice-changing recommendations.

2. Imaging and mechanistic substudy
   Data on infarct size, myocardial salvage index, microvascular obstruction (e.g., via MRI) would strengthen the mechanistic justification.

3. Long-term follow-up
   Outcomes beyond 30 days, especially mortality, heart failure, recurrent events, and bleeding, are crucial for clinical decision-making.

4. Dose optimization
   Head-to-head comparisons between the 0.110 and 0.130 mg/kg doses may reveal the optimal balance of efficacy and safety.

5. Regulatory submissions and pathway
   If CELEBRATE is robust, an NDA submission to FDA (and equivalent agencies globally) is likely, possibly paving the way for label expansion beyond STEMI.

6. Implementation trials
   Real-world trials evaluating cost-effectiveness, EMS workflow integration, and impacts in diverse healthcare systems will be critical.

7. Exploration beyond STEMI
   The design may be extended to high-risk non–ST-elevation ACS, or even ambulatory high-risk patients as a prophylactic measure (although that is speculative).

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Conclusion

The positive top-line results from CELEBRATE mark a potential paradigm shift in STEMI care: bringing high-grade, rapid platelet inhibition to the point of first medical contact. If the full data uphold the safety and efficacy signals, zalunfiban (Disaggpro) could become the first antiplatelet therapy routinely deployed before hospital arrival in STEMI. That said, encouraging reports must be weighed cautiously—detailed peer-reviewed data, external validation, and implementation studies will ultimately determine whether this innovation becomes standard practice.

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Key Takeaways

• The CELEBRATE trial has reported that prehospital subcutaneous zalunfiban met its primary efficacy and safety endpoints in STEMI patients receiving it via EMS prior to PCI.

• Zalunfiban’s pharmacologic profile—rapid onset, short duration, and subcutaneous administration—is purpose-built for early intervention during transport.

• The trial’s 7-point clinical composite endpoint and FDA alignment with an NDA-enabling design underscore its regulatory and clinical ambitions.

• Pending full data release, key questions remain about absolute benefits, bleeding risk, operational logistics, and long-term outcomes.

• If validated, this approach could alter the standard of care by compressing the timeline from symptom onset to effective platelet inhibition, particularly in settings with delayed hospital access.