John M. Mandrola, MD after the ORBITA-2 trial “saved interventional cardiology” by confirming that PCI is really better for angina than a placebo.

Cardiology

Cardiac Wire’s Top Six Takeaways from AHA 2023

The AHA 2023 Scientific Sessions are officially complete. We hope you had a blast if you attended, and had a great weekend if you stayed home. We also hope you enjoy Cardiac Wire’s top-six takeaways from cardiology’s last big event of 2023:

• SELECT Dominates – AHA 2023 kicked off with the full results from Novo Nordisk’s SELECT trial – and semaglutide’s ability to slash cardiovascular events was still what everyone was talking about as the Scientific Sessions wrapped up on Monday. Many attendees still aren’t totally comfortable with GLP-1s, but most would agree that these drugs are about to have a massive impact on cardiology.

• A New Anticoagulation Factor – An impressive Late Breaker featuring Anthos Therapeutics’ Factor XI inhibitor abelacimab (see coverage in The Wire section) and a strong presence from Bayer and Janssen/Bristol Myers Squibb’s Factor XI research teams had many attendees considering a future where bleeding risks aren’t keeping millions of AFib and stroke patients from receiving anticoagulation meds. Depending on who you talk to, we could be headed towards a completely new anticoagulation standard of care.

• Prevention & Detection – Boosted by GLP-1 obesity buzz and the fact that cardiovascular outcome trends have been headed in the wrong direction, AHA 2023 placed a greater focus on prevention. That preventative focus seems to be bringing an embrace of a wider range of risk factors and risk detection methods (well beyond blood pressure and LDL-C).

• Treatment Evolution – That increased focus on detection might also be due in part to the incredible treatment evolution taking place, including for conditions that had no treatment options just a few years ago (e.g. ATTR-CM, obstructive HCM) and conditions that now have far more advanced treatment options (e.g. heart failure).

• Implementation Science – We have the tools to detect and treat far more diseases, so why are so many people living undiagnosed, and why are so many diagnosed people not receiving proper treatment? That question repeatedly came up during AHA, suggesting that the impact of the latest treatment advances will depend on similar advances in implementation science.

• Long-Term Solutions: A review of the most-discussed Late Breakers suggest that cardiology’s implementation science problems could be improved by embracing one-time (e.g. renal denervation, gene editing) or long-lasting therapies (e.g. zilebesiran, recaticimab). That said, there were still plenty of attendees who had major concerns about one-time therapies (especially gene editing), and many still aren’t sure that long-lasting therapies would solve our adherence problems.

The Takeaway

Cardiology faces its share of challenges, but AHA 2023 made it clear that plenty of solutions are on the horizon, and some of the smartest and most passionate people in medicine are ready to bring these solutions into patient care.

Check out the rest of today’s issue for details on the biggest trials from AHA 2023.

Automating Echo Amyloidosis Assessments

The University College London National Amyloidosis Centre is the world’s largest cardiac amyloidosis care provider, making their echo assessments both crucial and high-labor. See how UCL researchers used Us2.ai’s AI echo software to accurately analyze echos from 1,200 patients with ATTR Amyloidosis in 24 hours, without requiring human interaction.

The Behavioral Science Behind Change Cardiology Hemo

When Change Healthcare set out to design its next-generation Cardiology Hemo monitoring system, they put behavior science at the heart of its product strategy. See how Change’s UX designers applied its behavioral science team’s findings to improve its Hemodynamics solution to help make physicians and technicians even more efficient.

The Wire

• SELECT Trial Stars at AHA 2023: The full results from Novo Nordisk’s SELECT trial on semaglutide’s ability to reduce cardiovascular events absolutely dominated AHA 2023. Although semaglutide’s 20% five-year MACE reduction was already announced in August, the full results also revealed data on its absolute MACE risk reduction versus placebo (-1.5%; 6.5% vs. 8%) and a “pretty good” number of people needed to treat to avoid one event (67). Semaglutide patients had similar serious adverse events as placebo-takers (33.4% vs 36.4%), but way more discontinuations due to adverse events (10% vs 2.0%).

• PCI Officially Improves Angina Symptoms: Interventional cardiologists breathed a collective sigh of relief at AHA 2023, after the ORBITA-2 trial showed that PCI does indeed improve stable angina symptoms. The researchers randomized 301 patients who were receiving little or no antianginal medication to either undergo PCI or take a placebo, finding after 12 weeks that the PCI group had a lower angina score (2.9 vs. 5.6) and fewer cases of ACS (4 vs. 6 patients). These results surprised few, but its potential implications for PCI procedures and interventional cardiology got plenty of people’s attention.

• Abelacimab’s Dramatic Bleeding Data: Details of the AZALEA-TIMI study, comparing Anthos Therapeutics’ Factor XI inhibitor abelacimab against rivaroxaban (J&J’s Xarelto), were released at AHA 2023 following a top-line release in September. What’s new? In the study of 1,287 patients with mild or moderate stroke risks, the rate of major or nonmajor bleeding was 67% lower with abelacimab (2.7 vs. 8.1 per 100 patient-year), while rates of major bleeding and gastrointestinal bleeding were 74% and 93% lower with abelacimab.

• Cleerly Looks to Transform Personalized CVD Care: Cleerly is launching perhaps the first large-scale randomized imaging AI trial, as it seeks to prove that AI-guided cardiovascular care reduces heart attacks. The five year TRANSFORM trial aims to enroll 7,500 patients (100-200 US sites) who have CVD risk factors, but not heart disease. The investigative arm will receive treatments based on results from Cleerly’s investigational AI-based plaque staging system at baseline and 24 months, and the usual care arm will be treated based on their CVD risk factors.

• AHA AI Innovator Panel: Amid all the pharma-focused AHA Late Breakers was a compelling panel on AI’s current and future impact on cardiology, featuring a roster of leaders from the trenches of cardio AI (Cleerly’s James Min, MD, AccurKardia’s Juan C. Jimenez, AliveCor’s David Albert, MD., and more). The conversation revealed some key insights into why more cardiovascular AI use is coming, including: 1) CVD is too often “detected” after patients have major events, 2) Significant therapy advancements require similar advancements in AI-based detection and staging, 3) AI’s value will be driven by how well it’s implemented into workflows.

• VERVE Cuts LDL, Raises Concerns: AHA 2023 brought new evidence that gene editing can reduce LDL-C in patients with HeFH, while also reinforcing concerns about the treatment. The phase 1b trial used Verve Therapeutics’ VERVE-101 CRISPR editing to inactivate the PCSK9 gene in ten patients with HeFH and ASCVD. The three patients treated with therapeutic doses (0.45, 0.45, 0.6 mg/kg) had 39%, 48%, and 55% LDL-C reductions, although two of those patients had severe cardiac events (MI after one day, cardiac arrest after 5 weeks) and several recorded increases in liver transaminases.

• Cutting LDL-C Doesn’t Drive Cognitive Declines: Open-label extension study data for the PCSK9i evolocumab (Amgen’s Repatha) might alleviate concerns about the cognitive risks of reducing LDL-C. In a sub-study of 306 patients in the FOURIER trial followed for about five years, their median LDL-C was reduced to 34 mg/dL, but they experienced no significant change in the spatial working memory strategy index of executive function scores (SWMI). Among 152 patients, there was no significant change in SWMI from baseline up to 7.2 years.

• Should We Treat Subclinical AFib? Treating subclinical AFib with the oral anticoagulant apixaban (Bristol Myers Squibb’s Eliquis) can reduce the risk of stroke by 37%, but at what cost? That’s the question people are asking following the ARTESIA study presented at AHA. Of 4,012 patients with subclinical AFib, 55 patients (0.78% per patient-year) on apixaban had a stroke compared to 86 on aspirin (1.24% per patient-year). However, rates of major bleeding were 1.71% per patient-year with apixaban versus 0.94% per patient-year with aspirin.

• Quarterly PCSK9i Dosing Works: AHA 2023 brought positive Phase 3 data for the long-acting PCSK9 injectable recaticimab (Jiangsu Hengrui Pharmaceuticals), which is dosed every 1-3 months. In the REMAIN-2 study of 689 people with high cholesterol, those dosed every four and twelve weeks with recaticimab had 59% and 51% LDL-C reductions, versus 0% and +2% with placebo. Safety data were similar. Putting the positive results aside, some at AHA questioned whether long-term dosing actually improves compliance. 

• iCardio.ai in Butterfly Garden: Echo AI startup iCardio.ai announced that its AI suite will be compatible with Butterfly Network’s famed handheld ultrasound and will be included in its recently launched Butterfly Garden AI marketplace. iCardio.ai’s FDA 510(k)-pending AI suite produces a preliminary echo report, with dozens of heart measurements, detection of valvular disease, and image quality assessments. 

• Zilebesiran’s Six-month BP Control: Detailed data from the KARDIA-1 study presented at the AHA meeting, support Alnylam’s RNAi drug zilbesiran’s potential to control blood pressure via a single subcutaneous injection every six months. In the dose-ranging study of 394 patients with average systolic BP of 142 mm Hg, zilbesiran’s change versus placebo ranged from -11.1 mm Hg for 150 mg to -14.2 mm Hg for 600 mm Hg. Alnylam recently announced the trial met its endpoints, but didn’t provide details before AHA.

Optimizing Your Post-Processing Workflow

The growth of cardiac CT and CMRI volumes and continued shortages in the imaging technologist workforce can mean big challenges for imaging organizations. Join this Cardiac Wire Show starring Precision Image Analysis’ Jim Canfield and Cleveland Clinic’s Scott D. Flamm, MD, MBA to see how outsourcing cardiac image post-processing can solve this problem, while improving efficiency, accuracy, and standardization.

Measuring True Cardiac Risk

How can AI help physicians “see” beyond conventional lipid profiles? Tune in to this on-demand webinar showcasing how Cleerly’s AI-QCT solution complements conventional approaches to evaluating heart disease risk factors, and improves coronary artery disease diagnosis and heart attack risk assessments.

The Resource Wire

• A Solution for Your Entire Cardiology Service Line: The pace of change in healthcare can be dizzying, creating new and more complex challenges for cardiology departments to overcome. See how Merge Cardio and Merge Hemo can turn those challenges into opportunities for greater workflow efficiency and improved care.

• Evolving Coronary Disease Imaging Pathways: HeartFlow’s PRECISE trial showed that their precision approach for evaluating stable chest pain avoids unnecessary testing and improves care – without risking missed heart disease diagnoses. In this Cardiac Wire Show, HeartFlow’s Chief Medical Officer Dr. Campbell Rogers dives into the PRECISE trial results and its implications for clinical practice.

• How to Identify and Treat More CVD Patients: Do you know how many patients with high CVD risks are in your chest CT archive? See how the Stanford Health Care System used Bunkerhill Health’s Incidental CAC algorithm to screen its previous non-gated chest CTs, identify patients with coronary calcium, and get them on statins.

• Precision QRS Detection: QRS detection is essential for any ECG algorithm, and Monebo’s Kinetic QRS ECG Algorithm sets the standard for accuracy. Kinetic QRS accurately detects the QRS complex, no matter the amplitude, waveform, or noise levels.

• Experience the future of learning: Medtronic Academy 2.0 is here! Unlock your ultimate destination for structural heart medical education with the newly redesigned Medtronic Academy 2.0. Gain access to expert-led courses, webinars, and a wealth of resources to stay ahead in cardiovascular care. Visit now!