Damian Fogarty, MBBS after a Phase 1 study showed that one zilebesiran injection can control BP for six months.

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Cardiology Pharmaceuticals

Zilebesiran’s Long-Lasting Antihypertensive Potential

Could the first long-lasting antihypertensive medication be on the way? Results of a Phase 1 study in NEJM suggests that Alnylam Pharmaceuticals’ zilebesiran is a frontrunner to become that drug, showing that a single injection controls blood pressure for up to six months.

Zilebesiran is an investigational RNA interference therapeutic agent that inhibits hepatic angiotensinogen synthesis, which plays a key role in the development of hypertension. 

• That’s how zilebesiran works, but most news headlines and social media comments focused on how long it works, noting the BP control challenges created by poor adherence to daily antihypertensive pill regimens.

The Phase 1 study included 107 adults with hypertension and was performed in three parts, evaluating zilebesiran at different doses, with specific salt intake diets, and when combined with other hypertensives.

• Zilebesiran use was associated with dose-dependent serum angiotensinogen level reductions that sustained over six months
• A ≥200 mg dose of zilebesiran reduced systolic (>10 mm Hg) and diastolic (>5 mm Hg) blood pressure by week 8, which was consistent during day and night, and sustained over six months
• A 800 mg dose of zilebesiran drove the greatest average systolic and diastolic BP reductions (22.5 mm HG & 10.8 mm HG) at month 6
• Zilebesiran’s BP reductions were diminished among participants with high salt diets
• BP reductions were greater when zilebesiran was combined with the BP drug irbesartan 

Adverse events were less common in the zilebesiran group than placebo (72% vs. 88%), most of which were mild or moderate, and there were no reports of hypotension, hyperkalemia, or worsening of renal function.

Although the study was short and small, and some aspects of zilebesiran’s efficacy and safety aren’t confirmed, the authors found these antihypertensive results to be strong enough to justify further research. 

Zilebesiran’s impact might also go beyond BP control, as the associated NEJM editorial suggested that it could also be able to treat other conditions related to renin-angiotensin activation such as kidney and heart disease.

The Takeaway

Although zilebesiran has a lot more to prove, these initial results are promising. And the adherence benefits of a long-lasting antihypertensive drug seems even more promising, once one is developed and approved.

The HeartFlow Story

Shifting the standard of care is a monumental undertaking, and yet physicians across the globe are embracing HeartFlow’s FFRct Analysis. Hear from the co-founder how HeartFlow got its start, and why physicians love it.  

Monebo’s AF ECG Algorithm

Atrial fibrillation is often difficult to characterize with an automated algorithm due to the changing waveform morphology, system, or muscle noise. This is especially true given the size constraints of ambulatory devices to detect AFib. See how Monebo’s Kinetic AF ECG Algorithm overcomes these size limitations without sacrificing accuracy.

The Wire

• Pfizer & Riparian’s Vasoprotection Agreement: Pfizer and Riparian Pharmaceuticals announced a license and research agreement, giving Pfizer exclusive rights to one of Riparian’s preclinical programs focused on novel vasoprotective cardiovascular therapeutics – plus future licensing options. In exchange, Pfizer will make upfront and milestone payments, pay royalties on sales of any resulting therapeutics, and support Riparian’s efforts to discover additional vasoprotective drug targets. 

• Complete Revascularization for Angina: New analysis of the ISCHEMIA study suggests that complete revascularization is superior to incomplete revascularization and conservative therapy for treating angina. The study looked at 5,179 patients with chronic coronary disease and moderate ischemia, including 1,641 who underwent invasive management. Only about half of the invasive management group achieved complete revascularization, but those who did largely experienced greater symptom and health status improvements compared to the other approaches.

• Abiomed Impella Recalled Again: Abiomed’s Impella heart pump is the target of its second FDA Class I recall in two months due to safety issues when used with TAVR patients. Abiomed recorded 27 cases where TAVR struts collided with the Impella device’s spinning impeller, representing 0.7% of TAVR patients who have been treated with an Impella system since 2016. Abiomed won’t actually retrieve Impella devices from hospitals, and instead will update its instructions. The previous recall involved issues with purge fluid leaks.

• MRI Combo for HCM Detection: A combination of two MRI scanning protocols might help detect hypertrophic cardiomyopathy (HCM) before symptoms appear. UK researchers performed cardiac diffusion tensor imaging (cDTI) and cardiac perfusion MRI in 206 patients, finding that people with HCM had altered heart microstructure and microvascular disease (P<0.01). They also found that MRI-based microstructural cardiac abnormalities were present carriers of a genetic mutation for HCM.

• Cardiology Private Equity On the Rise: Bailey & Company highlighted the rise of private equity cardiology practice acquisitions, counting nine acquisitions between January and June 2023, nearly matching 2021 and 2022’s full-year totals (10 & 11), and surpassing 2018-2020 (6 in 3yrs). The firm attributed the increased PE interest to rising CVD rates and CMS’ expanded outpatient cardiology coverage, while attributing rising valuation multiples to the limited supply of independent cardiology practices. Unsurprisingly, PE firms are favoring practices that cover multiple subspecialties and own at least one ASC or cath lab.

• But Does Private Equity Harm Patients? A new study in The BMJ suggests the answer is Yes, at least when it comes to cost and quality of care. Researchers performed a meta-analysis of 55 studies over the past 20 years, most looking at PE investment in nursing homes and hospitals. Nine of 12 studies looking at costs showed higher costs to patients or payors with PE ownership. Of the 27 studies that assessed care quality, 12 found harmful impacts (reduced staffing, shift to lower nursing skill mix), three found beneficial impacts (operational efficiencies), nine found mixed impacts, and three were neutral.

• BVS Scaffolds’ 3-Year Struggles: Data from the ABSORB IV trial shows that Abbott’s discontinued Absorb bioresorbable vascular scaffolds (BVS) performed worse than the company’s Xience cobalt chromium everolimus-eluting stents (CoCr-EES), even after adopting an improved BVS implant technique. Among 2,604 patients with ACS, BVS had higher 5-year target lesion failure (17.5% vs. 14.5%) and device thrombosis rates (1.7% vs. 1.1%). However, BVS challenges were isolated to the first three years, and the devices had similar event rates during the fourth and fifth years.

• CathVision Adds Another $9M: Electrophysiology analytics startup CathVision added $9M in funding (total raised now nearly $30M) to help expand its commercial operations and add more AI-based analytics to its ECGenius System. Positioned as a modern reimagination of EP recording systems, the FDA-cleared ECGenius System uses proprietary hardware and AI to capture clean EP signals and provide electrophysiologists with automated analysis during cardiac ablation procedures.

• Cardiology, The Imaging AI Market Leader: Signify Research estimates that the medical imaging AI market increased by 15% to $576M in 2022 and will soar to $1.73B by 2027 – with cardiology AI leading all clinical segments throughout both periods. Cardiology AI tools generated $192M in global revenue in 2022 for a 33% share of the imaging AI market, and are forecasted to maintain that 33% share through 2027 when cardiology revenues would surpass $570M.

• TTE AI for LAT Detection: A Poland-based team developed an AI model that uses transthoracic echo (TTE) images to detect left atrial appendage thrombus in patients on chronic oral anticoagulants, potentially avoiding uncomfortable transesophageal echo exams (TEE). The researchers trained the model using 2,827 TEE exams and tested it with TTEs from 1,284 patients at two sites, finding that the TTE AI model spotted LAT in 5.5% of patients and could spare 40% of patients from undergoing TEE exams without missing any thrombus.

• Big Tech Fights AI Healthcare Regulation: Tech giants including Google, Amazon, and Epic are pushing back against proposed AI regulation that would increase oversight of tools guiding patient care. While the ONC wants training data publicly disclosed as part of federal certification, Epic argues that there would be less “incentive to innovate” if certified health IT developers “have to disclose publicly their intellectual property, while non-certified predictive model developers are not required to make the same disclosure.”

AI Echo Copilot – The Future of Echocardiography

New technology from Us2ai called Us2.connect allows you to add AI automation to any echo device. Any echo machine can now have 100% automated reporting with disease detection and editable measurements – all generated in realtime as you scan.

Cleerly Revealed What Other CAD Tests Couldn’t

“I could have had a heart attack.” Florida-based registered nurse, Sharon Bruno BSN, RN, had a zero CAC Score and no known heart disease symptoms, but she learned through Cleerly’s AI-enabled CCTA analysis that she actually had moderate plaque burden. See how Sharon’s proactive detection allowed her to make lifestyle changes early enough to reduce her CVD risks.

The Resource Wire

• Using an outsourced cardiac image post-processing solution doesn’t have to mean sacrificing control of the results. Discover how PIA’s customizable post-processing workflow can help you get the most out of your images.

• 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!

• Check out this Change Healthcare video discussing the importance of user experience in the adoption of structured reporting, and how it can lead to improvements in imaging speed, quality, and cardiologist workflow.