🫀 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.

---

🧪 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.

---

🔍 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.

---

💡 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.

---

🩺 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

---

✨ 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).

---

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.

---

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.

---

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.

---

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.

---

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.

---

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.

---

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.

---

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.

---

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).

---

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.

---

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.

Looming CMS Cuts Threaten Future of Cardiac Amyloidosis Imaging

 Introduction

The Centers for Medicare & Medicaid Services (CMS) has proposed a 57% reimbursement cut for pyrophosphate (PYP) scintigraphy, a cornerstone imaging test for diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM). This reduction, buried in the 2026 Hospital Outpatient Prospective Payment System (HOPPS) proposed rule, has triggered urgent protests from the American Society of Nuclear Cardiology (ASNC) and nuclear cardiologists nationwide. With the comment period closing September 15, the stakes are high: patient access, equity in care, and the very momentum of amyloidosis recognition and treatment may be jeopardized.

---

Why PYP Imaging Matters

PYP/amyloid imaging transformed amyloidosis from a rare diagnostic curiosity to a mainstream, noninvasive test. It allows cardiologists to confirm ATTR-CM without biopsy in nearly 85% of cases. This has fueled:

• Early detection of a disease more common than previously thought

• Recruitment into clinical trials of novel therapies

• Patient access to FDA-approved drugs such as tafamidis (Vyndamax/Vyndaqel, Pfizer), vutrisiran (Amvuttra, Alnylam), and acoramidis (Attruby, BridgeBio)

Importantly, PYP imaging does not require high-cost infrastructure; any center with a SPECT camera used for coronary artery disease stress testing can perform it—provided trained nuclear imagers are available.   

---

The Proposed Cut and Its Impact

CMS plans to reassign CPT code 78803—currently reimbursed at $1,305.48—to a lower ambulatory payment classification (APC), slashing reimbursement to $558.70. The rationale ties to a policy requiring separate payments for isotopes exceeding $630.

This broad reclassification ignores the relatively low isotope cost for PYP scans, yet still imposes the same drastic cut. Consequences include:

• Reduced institutional interest in offering the test

• Widening healthcare disparities, especially among underserved African American populations disproportionately affected by hereditary ATTR-CM

• Diminished clinical adoption at a time when amyloidosis programs are expanding nationwide

---

Expert Voices: A Growing Field at Risk

Leaders in nuclear cardiology warn that the cuts would be “devastating” for the field. Just a decade ago, ATTR-CM lacked effective treatments; today, the combination of PYP imaging and life-prolonging therapies has redefined patient care.

If implemented, the CMS proposal could:

• Stall further recognition of amyloidosis prevalence

• Threaten the nascent pipeline of amyloid programs in U.S. hospitals

• Undermine equitable access to diagnosis for at-risk populations

---

Policy Solutions on the Table

ASNC urges CMS to:

1. Delay reclassification of CPT 78803 until more data are available.

2. Consider a new dedicated CPT code for PYP imaging, separating it from unrelated and costlier nuclear medicine procedures.

3. Allow time for geometric mean cost data collection over several years before implementing cuts.

---

Key Takeaways

• PYP imaging is central to diagnosing ATTR-CM and enabling access to new therapies.

• The proposed 57% CMS cut would drastically reduce reimbursement, potentially stalling a field that has only recently gained momentum.

• Healthcare disparities could worsen, especially for underserved populations at higher risk.

• ASNC and nuclear cardiologists are calling for urgent action before the September 15 comment deadline, advocating for either delaying the cuts or establishing a dedicated CPT code to protect patient access and innovation.

AI-Powered Coronary Plaque Analysis Enhances CCTA, Changes Care, and Cuts Long-Term Costs: Insights from the DECIDE Registry

Introduction

As artificial intelligence (AI) continues to transform cardiovascular diagnostics, its integration into coronary CT angiography (CCTA) is showing compelling promise. The DECIDE registry, presented at the 2025 Society of Cardiovascular Computed Tomography (SCCT) meeting, demonstrates that AI-based coronary plaque analysis (AI-CPA) can lead to meaningful changes in clinical management for over half of symptomatic patients—while simultaneously reducing long-term costs. This marks a significant step forward in personalized cardiovascular prevention and risk stratification.

---

AI-Driven Insights Go Beyond Stenosis Severity

The DECIDE registry assessed the clinical utility of AI-enabled plaque quantification using a commercial platform (HeartFlow) in 972 symptomatic patients undergoing CCTA. The analysis remained blinded until 90 days post-index CCTA, at which point clinicians were provided AI-derived plaque burden and staging (mild, moderate, severe, or extensive).

• Primary finding: In 51.3% of patients, AI-CPA led to a change in medical management.

• Treatment escalations occurred in 36%, including increased statin dosing or new lipid-lowering therapy.

• Management changes were more frequent in patients with higher plaque burden, diabetes, hypertension, hyperlipidemia, and CT-FFR < 0.80.

This demonstrates how quantitative plaque analysis, independent of luminal stenosis, can recalibrate treatment intensity more effectively than risk calculators alone.

---

Better LDL Targeting and Lipid Control

In patients whose management changed, 44.1% started a new lipid-lowering agent, while 23.5% had dosage intensifications. Among those with serial cholesterol testing, significant improvements in LDL and HDL were observed only in patients who had management changes (P ≤ 0.01), reinforcing the downstream effect of AI-informed care on biomarkers and adherence.

---

Visualizing Disease for Patients and Providers

Physicians noted that AI-generated arterial images helped bridge the gap between diagnosis and behavior change, facilitating shared decision-making. Presenting visual evidence of coronary plaque, LDL targets, and personalized risk empowered patients to better understand their disease and adhere to medication.

“It simplifies the discussion into one or two sentences. Showing patients their actual arteries and plaque burden improves compliance,” one investigator noted.

---

Real-World Economic Value: $719 Saved Per Patient Over 10 Years

Using Medicare fee-for-service data from the FISH&CHIPS study, a cost-effectiveness model projected:

• All-cause mortality reductions of 0.3% to 1.1% over 3.5 to 10 years.

• Cost savings per patient of:

  • $263 at 3.5 years

  • $373 at 5 years

  • $719 at 10 years

These projections assume a one-time AI-CPA cost of $950 and account for downstream healthcare expenditures including PCI, ambulance transport, and inpatient care. Despite increased use of statins or PCSK9 inhibitors, the model suggests that upfront investments in AI-CPA are justified by lower event rates and hospitalizations.

---

Implications for Clinical Practice and Future Research

The DECIDE registry supports the growing sentiment that AI-augmented CCTA may soon redefine preventive cardiology. While long-term outcome trials are underway, the current findings suggest that quantifying coronary plaque offers actionable intelligence beyond traditional metrics.

"This isn’t just about plaque detection; it’s about precision therapy and early intervention," experts said. "We're witnessing the convergence of imaging and lipidology."

 

---

Key Takeaways for Busy Clinicians

• AI-based coronary plaque analysis (AI-CPA) changed management in over 50% of symptomatic patients post-CCTA in the DECIDE registry.

• Changes included new or intensified lipid-lowering therapies, which translated to better cholesterol control.

• AI-CPA improved patient engagement and provided a visual tool to guide shared decisions.

• Cost-modeling studies suggest $719 per patient savings over 10 years, despite the initial cost of AI analysis.

• These findings support broader adoption of AI-enhanced plaque staging to guide personalized secondary prevention.

---

References

• HeartFlow AI-Powered Coronary Plaque Analysis

• DECIDE Registry Overview

• TCTMD Conference Coverage

AI-Driven Coronary CT May Help Close Gaps in ASCVD Prevention, Especially for Women

 Introduction:

Despite decades of progress in the prevention of atherosclerotic cardiovascular disease (ASCVD), disparities persist—particularly in women. A promising innovation, AI-based quantitative computed tomography (AI-QCT), may offer a new solution. Recent results from the CERTAIN study, presented at the 2025 Society of Cardiovascular Computed Tomography (SCCT) meeting, suggest that AI-QCT may not only improve cardiovascular risk stratification but also influence therapeutic decision-making. However, a disconnect remains between AI-based recommendations and actual implementation in clinical practice.

---

How AI-QCT Is Reshaping Preventive Cardiology

AI-QCT, exemplified by platforms such as Cleerly, automates the quantification of coronary plaque burden from coronary CT angiography (CCTA). It stages plaque by total volume, helping identify high-risk patients earlier. In the CERTAIN study, 700 symptomatic patients from five US centers underwent AI-QCT, which generated personalized medication recommendations.

• Plaque staging:

  • Stage 0: No plaque (1%)

  • Stage 1: 0–250 mm³ (61%)

  • Stage 2: 250–750 mm³ (28%)

  • Stage 3: >750 mm³ (10%)

Physicians were unblinded to AI findings, and 61.6% of patients received new preventive therapy recommendations, most often statins and aspirin.

---

Real-World Implementation Remains a Barrier

Despite clear AI-guided recommendations, only 29.7% of patients actually initiated new medications by 90 days. The gap was especially wide for:

• Statins: Recommended for 30.1%, but only 7.7% filled prescriptions

• Aspirin: Recommended for 35%, with just 4.7% filling them

Importantly, these gaps were consistent across all plaque stages, underlining a system-wide issue in translating risk stratification into treatment.

---

Persistent Gender Disparities

Although AI-QCT generated similar treatment recommendations for women and men (59.8% vs. 60.9%), women were less likely to receive prescriptions:

• Prescription fill rate at 90 days:

  • Women: 25.8%

  • Men: 32.7% (P < 0.001)

• Overall uptake of preventive therapies:

  • Women: 43.2%

  • Men: 53.8% (P = 0.031)

This suggests a persistent gender gap in cardiovascular care, possibly exacerbated by under-recognition of risk and suboptimal follow-through in clinical settings.

---

Future Directions and the Role of Patient Engagement

One major limitation of the CERTAIN study is that AI-QCT results were not shared with patients. The study investigators speculate that empowering patients with their own imaging data may enhance treatment adherence and shared decision-making.

Additionally, while AI-QCT shows great promise, standardization across vendors remains a challenge, as different software platforms may yield different plaque volumes. The TRANSFORM study, due to report in 2028, aims to validate how AI-driven tools translate into better clinical outcomes.

---

Key Takeaways for Clinicians:

• AI-QCT shows promise in identifying patients at risk of ASCVD and guiding preventive therapy.

• A significant gap remains between AI-guided recommendations and actual medication use, especially for statins and aspirin.

• Women are less likely than men to receive prescribed preventive therapies, even when recommended by AI.

• Patient engagement and standardization of plaque quantification across vendors are critical next steps.

• Clinicians should consider using AI-QCT outputs in shared decision-making to enhance treatment adherence and outcomes.