🫀 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.