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CVD Biomarker Bust, SINGLE-AF, and Several FDA Clearances
By Viktor Zarev, Virginia Hunt
September 10, 2026
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Together with
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“Three major cardiovascular readouts in one month. Three different pathways, yet a similar story, the biomarkers moved, but the clinical outcomes didn’t. Perhaps a sign that the biology is more complex than the biomarkers suggest or that today’s standard of care has already absorbed much of the risk these targets were meant to address.”
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Venkat Kris, Chief Scientific Officer at Alloy Therapeutics on Novo and Novartis’ CV drug trial failures.
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Sometimes good science means admitting a hypothesis was incorrect. Other times, it dashes our hopes of an easy target. Either way, today’s top story is a testament to what getting it wrong teaches us.
Thanks for reading,
Vik
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Cardiology Pharmaceuticals
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Cardiology just took back-to-back blows to two of its most promising prevention strategies. One drug for lowering lipoprotein(a) and another targeting interleukin-6 both failed in major trials, even as fresh data reaffirms just how much those factors matter.
This begs the question: are these molecules CVD causes or merely biomarkers?
- First, Novartis announced that pelacarsen, its Lp(a)-lowering drug failed to show a CV risk benefit in its 7-year, 8,000-patient Phase 3 trial.
- Then, Novo Nordisk decided to abandon its IL-6 inhibitor ziltivekimab across multiple trials after the ZEUS study showed the drug failed to provide a meaningful MACE benefit.
Not to be dramatic, but Novartis’ Phase 3 pelacarsen failure genuinely stunned cardiologists.
- That’s because an earlier study showed the drug cut Lp(a) by 80%, making future CV benefits seem certain.
- Now its failure casts doubt on similar trials underway at Amgen and Eli Lilly.
- Some physicians called it a “big bust” while others quickly criticized everything from the drug’s design to the trial’s patient population.
Novo’s IL-6 collapse was less of a blindside but the company’s decision to wrap up the Hermes and Athena heart failure trials early due to ZEUS’ failure rains heavily on the inflammation parade.
- Analysts once dubbed ziltivekimab a $3B drug, due to its ability to effectively lower IL-6 levels.
- But Novo’s choice to jump ship undercuts that potential alongside the inflammation-driven CVD hypothesis.
- Novo’s last ziltivekimab trial standing is Artemis, a post-MI trial reading out in the first half of next year.
Ironically, the science backing these studies looks stronger than ever. A recent JAMA study reinforced both risk factors and even tied them together.
- That study found that IL-6 significantly modifies Lp(a)-associated coronary artery disease risk.
- As a result, patients with the highest combined Lp(a) and IL-6 levels faced a 34% higher CAD risk than those with lowest levels.
- Thus, it seems like the two pathways interact, and inflammation amplifies Lp(a)’s danger.
The Takeaway
Here’s the moral of the story – strong association is not causation, because both pelacarsen and ziltivekimab successfully lowered their respective biomarkers but didn’t change cardiovascular outcomes. With these trial failures, it might be time to reconsider our understanding of CVD risk factors and the molecules we target to fight heart disease.
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How to Streamline Your Reporting Process
Like many medical centers, Baystate lacked a single cardiovascular database to streamline the documentation process and ensure accuracy. Read this Optum case report to learn how Baystate improved its percentage of unsigned charges within a 5-day window from a high of 89% to under 10%.
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Heart Failure Places Enormous Strain on our Healthcare Systems and Patients
There are 3.7 million US patients with HFpEF or HFmrEF, with prevalence only expected to rise. To learn more about the heart failure landscape and Bayer’s commitment to addressing patient unmet need, watch the video here.
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CA Diagnosis Using Echo AI
Diagnosing cardiac amyloidosis using echo can be challenging due to the imaging overlap between CA and more prevalent causes of cardiomyopathy. Read more about how Us2.ai’s echocardiographic score and fully automated deep-learning model overcome this challenge to enable better diagnosis.
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- Pacibekitug Plummets Inflammation: Despite today’s top story, the game’s still on to see if anti-inflammatories can provide cardioprotection, with a new IL-6 antibody offering its own promising results. Novartis’ Phase 2 pacibekitug study randomized 143 CKD patients to the monoclonal antibody or placebo and showed that pacibekitug led to dose-dependent reductions in CRP (+7% placebo vs. −76% 25 mg, −85% 50 mg). But as we discussed above, lowering inflammation hasn’t been shown to reduce MACE risk, so we’ll have to see if pacibekitug’s future clinical results can deliver a rebuttal.
- Another Impella Controller Alert: Yet again, the FDA issued an early alert after Johnson & Johnson’s Abiomed subsidiary recommended removing all Automated Impella Controllers due to purge cassette recognition issues stemming from failures of the purge flag component. These controllers serve as the primary user interface for the Impella heart pump, so servicing will be needed to make them safe again. As of August 17, Abiomed reported 37 serious injuries and three deaths tied to the issue.
- OAC for Intermediate-Risk AFib? We’re seeing a growing clinical trend in cardiology – with all the therapeutic options available, no treatment is one-size fits all. That sentiment also applies to AFib after the SINGLE-AF trial randomized 1.8k AFib patients classified as having an intermediate stroke risk to DOAC or no anticoagulation, finding that the DOAC group had a marginally lower composite rate of stroke, systemic embolism, major bleeding, or CV death (0.5% vs. 1.5%). This means that DOAC can be beneficial, but its effectiveness is likely modified by individual risk factors.
- Relaxin the Heart: A synthetic version of the peptide hormone that loosens muscles during pregnancy helped failing hearts regain function in a Phase 2 study. AstraZeneca’s relaxin agonist (yes it’s really called relaxin) reduced markers of cardiac remodeling and strain in heart failure patients with minimal side effects. Novartis, Eli Lilly, and Moderna have shelved similar drugs for clinical and financial reasons, but there’s hope yet for a relaxin-based heart failure therapy.
- Heartvue’s AI Imaging Approval: Cardiologist-founded Heartvue.ai earned its first FDA approval for an AI-enabled cardiovascular MRI platform called Heartvue.Proton. The software independently streamlines measurement and analysis of 2D linear dimensions, ventricular volumes, ejection fraction, and blood flow while still giving cardiologists the final say on reports. The platform may not be the only time-saver here: The FDA’s clearance also included a Predetermined Change Control Plan, which allows Heartvue to update the machine learning solution without having to go through another approval process.
- Updated CCTA Guidelines: Since 2014, CCTA has moved from a helpful diagnostic test to the gold-standard for non-invasive CAD detection. Now the SCCT’s updated guidelines reflect that shift, plus the growth of new CCTA technologies that move beyond stenosis into factors like plaque burden and non-atherosclerotic abnormalities. Reporting those factors became easier when CAD-RAD 2.0 was released in 2022, and now the standardized framework is also incorporated into SCCT’s updated guidelines. The update also touches on topics from imaging artifacts to artificial intelligence.
- CSP Keeps Pace With BiV: Biventricular pacing (BiV) is the recommended go-to for cardiac resynchronization therapy, but a JACC study showed conduction system pacing (CSP) could be just as effective for some patients. Among 150 patients with HFrEF and left bundle branch block randomized to either BiV or CSP, the average reduction in left ventricular end-systolic volume was nearly identical (34% BiV vs. 35% CSP). The methods also showed similar improvements among fitness, symptoms, and LVEF, but larger trials are needed before CSP can be viewed as BiV’s equal.
- FDA Clears an Expanded Cardiac Imaging Platform: LUMA Vision received expanded FDA clearance for its VERAFEYE procedural intelligence system for cardiac ablation. The clearance now allows LUMA to unify imaging, visualization, catheter tracking, and guidance into a single platform. It works by using one 360° imaging catheter to reconstruct real-time 3D models of the atria with CT-like accuracy. This lets physicians document where the ablation is delivered while using electromagnetic tracking to continuously know the position of both imaging and ablation catheters.
- Implicity Raises $40M for U.S. Push: Remote patient monitoring software company, Implicity, secured a $40M financing round to fund its next phase of U.S. growth. The funds will back commercial hiring, U.S.-specific features, and continued AI development. Implicity’s AI software aggregates and analyzes cardiac data across device manufacturers, and has shown it can lead to a 26% mortality reduction versus conventional monitoring. THe company also has an FDA-cleared heart failure prediction algorithm, and an ECG analyzer that can reduce false alarms by up to 76%.
- CRISPR Cholesterol Fix Holds at One Year: A Cleveland Clinic Phase 1 first-in-human trial found that CRISPR Therapeutics’ CTX310, a one-time gene-editing therapy, durably lowered LDL-C and triglycerides in patients with medication-resistant lipid disorders. Among 15 patients, the highest CTX310 dose cut LDL-C by 52.5% and triglycerides by 47.8% from baseline with the effects lasting throughout the study’s 12 month follow-up. No serious therapy-related adverse events were reported even though the infusion works by switching off the liver’s ANGPTL3 gene.
- Functional Angio for STEMI: The body of evidence is building when it comes to functional guidance for STEMI revascularization. Researchers in the AIR-STEMI trial randomized 1.8k STEMI patients with multivessel disease to revascularization guided by either functional coronary angiography or conventional angiography and found that the physiology-guided group had a lower composite rate of death, MI, stroke/TIA, or ischemia-driven revascularization (8.9% vs. 13.7%). Physiology guidance also reduced the risk of contrast-associated kidney injury or major bleeding (4.6% vs. 7.1%).
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Fujifilm’s Ultrasound for every Cardiovascular Ultrasound Environment
From academia to clinical diagnostics, versatility in cardiac ultrasound is essential. Discover why clinicians are choosing Fujifilm’s LISENDO 880 for exceptional image quality, comprehensive strain analysis, stress imaging, and innovative Virtual Contrast technology — all while delivering outstanding value.
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Merge Cardio 12.5 is Officially Available!
From AI-generated echo measurements to upgraded UI and reports, Merge Cardio 12.5 brings a long list of new innovations to the table. Find out more about how Merge Cardio’s latest version streamlines workflows to make your cardiovascular service line more cost-effective and patient-centered.
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State-of-the-Art Cardiac Monitoring at Scale
Cleared for 13 different heart rhythm interpretations, AccurKardia’s AccurECG 2.0 shortens the time from an arrhythmia incident to clinical intervention. Watch here to find out how AccurKardia and Specialized Medical are teaming up to bring the AccurECG 2.0 technology to clinicians across the U.S.
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- Canon’s 30 Years of Caring: For over 30 years, Canon has helped advance pediatric interventional cardiology through innovation and a commitment to better care. Learn more about how and why modern pediatric cardiac angiography came to be from one of its founding members, Dr. John P. Cheatham.
- The VASCADE MVP XL: Sometimes EP procedures call for a venous vascular closure system that is simply bigger. Haemonetics’ VASCADE MVP XL closure system comes with 58% more collagen and a 9% larger disc compared to the VASCADE MVP system as well as an expanded indication for utilizing 10-14F inner diameter sheaths.
- Redefining Cardiac Analytics: More data doesn’t equal deeper insight. There’s a fundamental distinction between measuring the timing of heart beats and understanding how the heart recovers electrically after each beat. Monebo is using that distinction to define the next frontier of cardiac analytics.
- Circle CVI’s cvi42 v6.5 is Now Live! Cardiovascular imaging plays a critical role in helping care teams with everything from prevention to procedural planning. That’s why Circle Cardiovascular Imaging released v6.5 of its cvi42 software with features like automated phase offset correction, editable plaque segmentation, and quantitative perfusion to support every aspect of CV imaging workflows.
- How AI Expands the Role of CMR Experts: If you’re an MRI technologist, AI could be the best thing that ever happened to your career. Read here to learn about the benefits of AI for CMR experts and how it can accelerate both your training and career.
- Outsourced Post-Processing with PIA: Behind each study is a patient whose care is a top priority. That’s why each PIA out-sourced imaging client is assigned a lead technologist responsible for ensuring study customization while allowing cases to be received 24/7 in a secure and scalable way.
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