C. Michael Gibson, MD

CeleBrate: Zalunfiban Administration at First Contact Improves STEMI Outcomes, With C. Michael Gibson, MD

Zalunfiban, a subcutaneous glycoprotein (GP) IIb/IIIa inhibitor in development by CeleCor Therapeutics for administration at first contact to patients with suspected 

ST-segment elevation myocardial infarction (STEMI)

, has met its primary efficacy and safety endpoints in the pivotal CeleBrate phase 3 trial.

GPIIb/IIIa inhibitors are the most potent antiplatelet drugs, blocking platelet aggregation induced by all activators including thrombin, thromboxane A2, and ADP. Most GPIIb/IIIa inhibitors must be delivered by an intravenous injection followed by continuous intravenous delivery with an infusion pump. However, zalunfiban can be administered rapidly – during the CeleBrate trial, patients received the medication at home, in the ambulance, or at a hospital emergency department.

 met with C. Michael Gibson, MD, an interventional cardiologist and the chief executive officer of the combined non-profit Baim and PERFUSE research institutes at Harvard Medical School, to discuss the implications of these data for the historically poor mortality rates in STEMI.

“When someone gets to the hospital, we do a great job getting them to the catheterization lab. It’s that time before they reach the hospital where we’re not doing as good of a job,” Gibson told 

. “Sadly, about half the deaths from heart attacks occur before someone even reaches the hospital. So, our goal was to really get the ball moving before someone hits the hospital door.”

CeleBrate is a phase 3, prospective, blinded, randomized, placebo-controlled, international multicenter study conducted at 45 locations worldwide. Patients were screened in the ambulance based on available information; male patients aged ≥18 years and post-menopausal females ≥50 years, weighing between 52 and 130 kg and with STEMI presenting with persistent ischemic chest pain (>10 minutes) and new ≥2 mm ST-segment elevation in 2 adjacent ECG leads within 4 hours were eligible for inclusion. Patients who had systolic blood pressure <90 mmHg and heart rate >100 bpm, who were being currently treated with renal dialysis, oral anticoagulation, direct oral anticoagulants, or thrombolytic agents, or who had a known history of ischemic or hemorrhagic 

Patients enrolled in the trial were randomly assigned in a 1:1:1 ratio to a single subcutaneous dose of zalunfiban 0.11 mg/kg or 0.13 mg/kg, or placebo. The primary efficacy endpoint was a hierarchical proportional odds model ranking 7 endpoints from worst to best. These included all-cause death, stroke, recurrent myocardial infarction, acute stent thrombosis, new-onset or re-hospitalization for 

, larger infarct size, or no endpoint through 30 days.

Ultimately, 2467 patients were included in the trial, with 853 receiving zalunfiban 0.11 mg/kg, 818 receiving zalunfiban 0.13 mg/kg, and 796 receiving placebo. The primary efficacy endpoint was substantially improved in the zalunfiban arm (adjusted odds ratio [OR], 0.79; 95% CI, 0.65-0.98; 

 = .028). Additionally, investigators observed no difference in the primary safety endpoint of GUSTO severe bleeding (1.2% vs 0.8%; 

= .4); however, GUSTO mild to moderate bleeding was increased (6.4% vs 2.5%), as was access site bleeding (9.4% vs 4.4%). Coronary blood flow was significantly faster in the zalunfiban treated groups on arrival to the cardiac catheterization laboratory (median 109 vs 176 frames, 

“A lot of people show up at a hospital that’s not equipped to do primary PCI, and they must be transferred. That often takes more than 2 hours from when they had symptoms,” Gibson said. “We’re not meeting the guideline recommendations in >80% of patients. This drug could really help improve outcomes in those patients, because it can increase the odds that the artery will be opened while you transfer that patient.”

In a press release regarding the study, CeleCor Therapeutics announced their intent to file a New Drug Application for zalunfiban with the US Food and Drug Administration in early 2026.

CeleCor Therapeutics. Rapid zalunfiban treatment at 1st point of medical contact lowered risk of more severe heart damage in combination with other serious heart-attack complications. November 10, 2025. Accessed December 2, 2025. 

https://www.celecor.com/rapid-zalunfiban-treatment-at-1st-point-of-medical-contact-lowered-risk-of-more-severe-heart-damage-in-combination-with-other-serious-heart-attack-complications/

van ‘t Hof A, Gibson CM, Rikken S, et al. Zalunfiban at First Medical Contact in Patients with ST-Segment Elevation Myocardial Infarction. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

CeleCor Therapeutics. A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (CELEBRATE). ClinicalTrials.gov Identifier: NCT04825743. Updated October 23, 2025. Accessed December 2, 2025. 

https://www.clinicaltrials.gov/study/NCT04825743

Videos

Gibson discusses the promising improvements to the composite primary endpoint of mortality, stroke, and recurrent MI as a result of zalunfiban treatment.

Dr Taub, Dr Patel, and Dr Kohli look ahead to the future of the management of cardiovascular risk and hyperlipidemia

Looking Into the Future of Lipid Management

The experts envision increased use of targeted therapies like siRNA that allow less frequent dosing for hypercholesterolemia and other conditions. Exciting data on “one-and-done” gene editing may enable permanent PCSK9 inhibition in familial hypercholesterolemia. Such innovations promise elegant, well-tolerated long-term solutions.

However, while much progress is being made in developing novel therapies for cardiovascular prevention (“first mile” investigations), major global burden exists in implementation and uptake (“last mile”). Even long available treatments take about a decade to achieve 50-70% adoption. Thus, reducing health inequities and accelerating real-world access remains key.

Beyond scientific advances, addressing rising obesity rates holds great potential to impact cholesterol management and overall risk. With obesity now recognized as a disease, more aggressive multifactorial treatment may emerge, benefiting lipids as well. Lipoprotein(a) is also garnering increasing interest as a causal risk factor amendable to new targeted therapies that may soon demonstrate cardiovascular improvements.

In summary, the experts express excitement about the future scientific pipeline while emphasizing the immense implementation challenges ahead in equitable delivery of cardiovascular prevention. Realizing the full potential of powerful emerging therapies will require overcoming barriers in dissemination and uptake among diverse populations. Continued innovation in treatment must therefore be matched by innovation in health systems’ ability to connect the right interventions with the right patients.

This summary was AI-generated and edited for clarity and readability. 

Cardiologists discuss how to select the right treatment for your patient with hyperlipidemia

How to Select Between Available LDL-C Lowering Therapies

The experts discuss considerations around selecting non-statin therapies for high cholesterol, either as add-on options to maximally tolerated statins or alternatives for statin-intolerant patients. The choice depends on the degree of additional LDL lowering required to reach one's personalized LDL "end zone" or target.

If the LDL is not too far from goal, options like ezetimibe, which reduces LDL around 20%, may suffice. The new agent bempedoic acid lowers LDL 17-24% and has demonstrated cardiovascular event reduction in a large outcomes trial in statin-intolerant patients. For larger LDL reductions around 50-60%, injectable PCSK9 inhibitor immunotherapy like evolocumab and alirocumab may be utilized. The recently approved siRNA inclisiran, while highly effective at lowering LDL, lacks outcomes data thus far.

Contraindications are minimal with these newer agents apart from hypersensitivity reactions. However, small creatinine elevations are expected with bempedoic acid due to mild renal effects, while inclisiran and the PCSK9 monoclonal antibodies are not affected by kidney or liver dysfunction given their targeted mechanisms.

In summary, newer non-statin agents provide varying degrees of additive LDL lowering, allowing clinicians to appropriately intensify therapy depending on just how far a patient's LDL level stands from their recommended treatment target. Ongoing assessment of changing cardiovascular risk helps determine the appropriate LDL "end zone" to guide medication selection.

Expert cardiologists discuss the recent clinical trials results of the CLEAR-OUTCOMES trial and thee sub analysis on the inflammatory marker hcCRP.  

Clinical Trial Results on Novel Nonstatins Agents.

The experts discuss the CLEAR Outcomes trial results for the newer cholesterol-lowering agent bempedoic acid in statin-intolerant patients. This 14,000-patient trial included a mix of primary and secondary prevention patients and demonstrated a significant reduction in 3-point major adverse cardiovascular events (MACE). While LDL lowering was modest, the MACE reduction aligned with expectations based on the degree of LDL lowering. Bempedoic acid also reduced inflammation, measured by hsCRP, without increasing diabetes risk, unlike statins.

There was additional analysis showing more benefit in the 30% of trial subjects who were high-risk primary prevention patients. Notably, there was a reduction in all-cause mortality for bempedoic acid in these patients. This reinforces the concept of a continuum of residual risk, where apparently healthy people can still be at high latent cardiovascular risk in the absence of cholesterol lowering therapy.

Beyond LDL, the experts emphasize assessing residual inflammatory risk with hsCRP, residual thrombotic risk, residual cholesterol risk as measured by triglycerides for icosapent ethyl therapy, and emerging risk markers like Lp(a). They advocate a personalized approach to matching specific therapies to a patient's dominant driver of residual risk. This more holistic, multi-pathway framework for risk reduction stands to optimize outcomes compared to focusing on LDL alone.

C. Michael Gibson, MD

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