The American Heart Association on the need to introduce heart-healthy urban policies as city-living populations continue to surge.

Pharmaceuticals

Silence Therapeutics’ Zerlasiran Shows LP(a) Potential

Silence Therapeutics’ zerlasiran continued to demonstrate its lipoprotein(a) impact, as topline Phase 2 data showed that the injectable siRNA slashed LP(a) levels by over 90% through 36 weeks.

• Zerlasiran is a siRNA (short interfering RNA), designed to reduce LP(a) levels by “silencing” the LPA gene that tells the body to make the apolipoprotein(a) protein. 
• LP(a) is a common and potentially significant cardiovascular disease risk factor, although LP(a)-lowering therapy options are currently limited.

The double-blind placebo-controlled ALPACAR-360 study subcutaneously administered 300mg of zerlasiran every 16 or 24 weeks or 450 mg every 24 weeks to 178 patients with a median baseline Lp(a) of 215 nmol/L who are at high risk of atherosclerotic cardiovascular events.

• After 36 weeks, both doses saw 90% or greater median Lp(a) reductions compared to placebo, while revealing no new safety concerns.

Those results closely match zerlasiran’s Phase 1 trial, which found that patients who received 450mg doses saw a 99% reduction in Lp(a) levels at 90 days, which stabilized at a 90% reduction by 201 days.  

Zerlasiran’s initial Phase 1 and Phase 2 results could be further validated as the ALPACAR-360 study continues, including 48-week data that will show LP(a) reductions through the end of the treatment period and 60-week data that includes post-treatment and secondary endpoints.

The ALPACAR-360 study also adds to the growing evidence supporting siRNA’s potential for LP(a) reduction.

• Amgen’s injectable siRNA olpasiran slashed Lp(a) by as much as 100% in its Phase II trial, and has moved on to Phase III.
• Lilly’s injectable siRNA lepodisiran drove more than 90% LP(a) reductions that lasted almost a year in its recent Phase 1 study.
• Meanwhile, Lilly’s small molecule inhibitor muvalaplin also performed well in its Phase I trial, reducing LP(a) levels by up to 65%, and bringing 93% of participants below 50 mg/dL.

The Takeaway

Although zerlasiran still has plenty to prove, its Phase 1 and 36-month Phase 2 results suggest that it has the potential to be a powerful LP(a)-reducing option, adding to the massive momentum we’re seeing across the siRNA segment.

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!

AHA Honors Stanford & Bunkerhill’s Incidental CAC Paper

Stanford University’s paper exploring how Bunkerhill’s incidental CAC algorithm increased statin use won the American Heart Association’s 2023 Willerson Award for the best clinical paper published in Circulation this year. See how Bunkerhill’s incidental CAC impacted patient care here.

Ready for More Precise ECG Monitoring?

Monebo designs, develops, and licenses complex ECG algorithms for use in a wide variety of monitoring applications. If you’re a medical device developer, monitoring center, or system integrator see why Monebo might be right for you.

The Wire

• Praluent’s Pediatric Approval: The FDA extended Regeneron’s PCSK9 inhibitor Praluent (alirocumab) to include children aged 8 and older with heterozygous familial hypercholesterolemia (HeFH), expanding upon its adult approvals. Praluent is now indicated for use as an adjunct to diet and other LDL-C lowering therapies in children who still have dangerously high cholesterol. The expansion is supported by a RCT that showed pediatric patients taking Praluent had 31% lower LDL-C levels after 24 weeks.

• CABG EXCELs in Left Main Revascularization: In the latest battle between PCI and CABG, the EXCEL trial revealed that readmissions are more common after PCI than CABG for left main coronary artery revascularization (48.6% vs. 41.8% within 5 years). Adjusted stats also showed that PCI is an independent predictor for readmission (HR: 1.22), while readmissions have a far higher risk of all-cause mortality after PCI than after CABG (HRs: 5.72 vs. 2.72).

• Evolut Advantages: New analysis of the Evolut Low Risk Trial presented at CRT 2024 highlighted the Medtronic TAVR device’s economic and clinical advantages. A cost-effectiveness analysis showed that Evolut TAVR had a lifetime incremental cost-effectiveness ratio of $2,119 per quality-adjusted life year gained (under $50k = high economic value), while TAVR’s 30-day costs were $5,189 below SAVR ($45,887 versus $51,075). Meanwhile, the Evolut TAVR had lower four-year rates of all-cause mortality or disabling stroke than SAVR (10.7% vs. 14.2%), and significantly better hemodynamics (9.8 mmHg vs. 11.8 mmHg ).

• AHA Targets the Heart of the City: As the global urban population swells to two-thirds of humanity by 2050, a new American Heart Association policy statement urged efforts to adapt our cities for heart-healthy living. The statement primarily focused on the impact of “urban provisioning systems” (utilities, housing, green infrastructure, transportation), while targeting urban spatial planning and infrastructure upgrades as key strategies for improving urban heart health.

• Distinct Exercise Patterns in ATTR: Using exercise testing, researchers have found distinct impairment patterns in patients with transthyretin amyloidosis (ATTR). Among 506 patients, those with ATTR with cardiomyopathy or ATTR with both cardiomyopathy and polyneuropathy showed peak mean oxygen consumptions of 14.5 and 15.7 mL/kg/min, both significantly below healthy levels (>25 mL/kg/min). Additionally, peak VO2 and peak systolic blood pressure emerged as key predictors of survival in ATTR patients, with respective hazard ratios of 0.89 and 0.98.

• Healthcare Workers Lack AI Fluency: Amazon Web Services released new findings around the state of AI fluency among healthcare leadership and employees, based on survey results from over 4,600 respondents. Healthcare execs expect AI to boost productivity by up to 44%, and just over half believe improving workflow and outcomes will be the top AI productivity benefit. That said, 78% of healthcare employers said they lack knowledge on how to provide AI training to employees and only 9% of healthcare employees reported having “advanced” AI fluency.

• Resilia’s Real-World Success: Edwards Lifesciences revealed excellent real-world outcomes for its SAPIEN 3 Ultra RESILIA valve at CRT 2024. With over 10,000 patients analyzed across 800 sites, the latest SAPIEN TAVR valve had no paravalvular leak in 88.3% of patients treated with the 29mm size. Smaller SAPIEN valves exhibited equally impressive outcomes, with 20mm valves demonstrating mortality and stroke rates akin to larger valves over 3 years.

• Full AGENT DCB Data: JAMA published full results from the AGENT IDE study of Boston Scientific’s AGENT drug-coated balloon (DCB), just a few weeks after its FDA approval. Among 600 patients with ISR, AGENT DCB was superior to balloon angioplasty for target lesion failure (17.9% vs. 28.6%, the primary endpoint), while also outperforming balloon angioplasty on ischemia-driven target lesion revascularization (13% vs. 24.7%) and target vessel MI (5.8% vs. 11.1%). However, the coated balloons had a higher cardiac death rate (2.9% vs. 1.6%).

• Donepezil’s HF Benefit: The dementia and Alzheimer treatment donepezil could improve heart failure outcomes. That’s the takeaway from a study on hypertensive rats with CHF after MI, in which donepezil treatment improved 7-week survival rates from 41% to 80%. The acetylcholinesterase inhibitor also slashed heart rates and arterial hypertension, while reducing cardiac hypertrophy and coronary remodeling. 

• Conformal Claas’ Thrombosis Advantage: Conformal Medical’s Claas LAAO implant appeared less risky for device-related thrombosis than Boston Scientific’s Watchman FLX in a lab study presented at CRT 2024. In the study of six devices (three of each brand) inserted into an acute radiolabeled in-vitro blood loop system for 90-120 minutes, the Claas device demonstrated incomplete coverage with thinner thrombus and 44% lower platelet deposition. Conformal is now enrolling a randomized pivotal study evaluating the Claas LAAO implant.

• February Hospital Flash Report: Kaufman Hall’s February Hospital Flash Report showed a continuation from previous months, as average margins ticked up to 5.1% while the leading hospitals continued to separate from the pack. An interesting call out was that hospitals’ net revenue hasn’t risen as fast as gross revenue, which might reflect payors negotiating more aggressively and a further shift to VBC. Total expenses on a volume-adjusted basis improved despite the persistent climb in drug and supply costs, largely due to labor expenses getting reined in.

Advancing CAD Risk Assessments

When HeartFlow used its Plaque Analysis solution to analyze more than 11,000 CCTAs in the DECODE Study, the solution achieved 95% agreement with IVUS and led to changes in two out of every three patients’ treatment plans. See how HeartFlow Plaque Analysis can help you accurately assess your patients’ CAD risks and personalize their treatment

Transform CVIS Workflows

See why Merge Cardio is a 2024 Best in KLAS cardiology solution, and how it can help improve your cardiology workflows, simplify data collection, and automate cardiology reporting.

The Resource Wire

• Leveraging a Proven Echo AI Platform: Us2.ai has developed a promising new pathway for bringing custom echo AI applications into widespread clinical and commercial use – historically a challenge for algorithms produced by health systems and academic institutions. Find out how it worked in a Ugandan RHD program here.

• Can AI Improve How We Prevent Heart Disease Progression? Tune in to Cleerly’s upcoming webinar (March 19, 2pm ET) where study leaders will discuss how the landmark TRANSFORM randomized controlled trial will test whether an AI-personalized care strategy can outperform traditional risk factor management and prevent cardiovascular events.

• The Benefits of Outsourced Post-Processing: 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.

• TeraRecon’s Structural Heart Enhancements: Detecting and addressing mitral valve and LAA conditions can be challenging. Check out TeraRecon’s Structural Heart white paper and discover how improving workflow and pretreatment planning can streamline these processes and potentially improve patient outcomes.