John Mandrola, MD, on the ESC’s new guidelines restricting statin eligibility.

Preventive Cardiology

New Findings Reignite REDUCE-IT Concerns

The cardiology community is revisiting the controversial 2018 REDUCE-IT study in light of new evidence that suggests the study’s placebo, mineral oil, is harmful. 

REDUCE-IT researchers originally found that icosapent ethyl (IPE), a fish oil product, reduced the risk of major adverse cardiac events (MACE) in high-risk statin users. Researchers randomized 8,000 participants into an IPE group and a mineral oil placebo group, and tracked them over five years. 

The researchers determined that IPE reduced the relative risk of MACE by 25%, shocking the cardiology community. Some wondered if the differences in risk reduction were driven by adverse effects from mineral oil rather than the benefits of IPE.

In the latest analysis, researchers used stored blood samples from the 2018 REDUCE-IT trial to investigate important biomarkers and compounds in the inflammatory cascade. The IPE group had no significant changes over time. However, the mineral oil group saw increases in the following atherosclerosis-associated biomarkers:

• 16.2% for interleukin-6
• 28.9% for interleukin-1β
• 21.9% for high-sensitivity C-reactive protein
• 18.5% for lipoprotein-associated phospholipase A2

The authors were noncommittal when discussing how these findings should influence the original study’s conclusions. But electrophysiologist and This Week in Cardiology host John Mandrola, MD, said the authors were being “extremely cautious,” adding, “It isn’t the [IPE] that drove the results of REDUCE-IT, it was the harm of the control arm.”

Deepak L. Bhatt, MD, lead author of the REDUCE-IT study and senior author of the recent substudy, is unconcerned by the findings. In an interview with TCTMD, Bhatt explained that without the mitigating effects of IPE, both groups may have experienced worsening biomarkers during follow-up. He points out that the current study does not provide any true mechanistic insight. 

The Takeaway

The REDUCE-IT trial established fish oil product IPE as a crucial heart disease deterrent. But new evidence suggests that the placebo may have inadvertently increased heart disease risk factors, bringing the landmark study under scrutiny once again.

Us2.ai Automates the Fight Against Heart Disease

See how Us2.ai cuts echocardiography’s manual work, subjectivity, and turnaround times to automate the fight against heart disease.

Transformation Through Structured Reporting

Ready to realize the benefits of cardiovascular imaging structured reporting? Check out these quick and powerful Change Healthcare videos detailing the efficiency gains provided by structured reporting and what it takes to drive adoption.

The Wire

• Eko’s EMAS FDA Clearance: Smart stethoscope startup Eko announced the FDA clearance of its Eko Murmur Analysis Software (EMAS), an AI algorithm designed to improve the identification and diagnosis of heart murmurs. Performing with an overall sensitivity of 85.6% and specificity of 84.4%, EMAS works with the company’s smart stethoscope to accurately and consistently catch heart murmurs indicative of valvular heart disease. 

• CAD-RADS 2.0: A new expert consensus document, CAD-RADS 2.0, expands on the 2016 coronary CTA reporting guidelines. A critical update emphasizes that plaque burden should be estimated whenever present through visual assessment, segment involvement score, coronary artery calcium evaluation, or total plaque burden quantification. Other updates include new modifiers, including assessment of FFR-CT or myocardial CT perfusion when performed.

• PCOS & CV Complications: A new study in Journal of the American Heart Association found that people with polycystic ovary syndrome (PCOS) are more likely to have cardiovascular complications during childbirth. Researchers identified 71.4M childbirth hospitalizations, 0.3% of which were patients with PCOS (n=195k), and found that people with the hormone disorder were more likely to have diabetes, obesity, and dyslipidemia. Even after correcting for confounding factors, PCOS remained an independent predictor of CV complications, including preeclampsia, eclampsia, peripartum cardiomyopathy, and heart failure.

• Aetna’s Cardiac PET/CT Reversal: Aetna reversed its cardiac PET/CT policy and will cover the exams in the future. Aetna historically declined hybrid PET/CT for coronary artery disease evaluation, calling the exams “experimental/ investigational.” However, Aetna changed its policy following lobbying efforts from the SNMMI and ASNC. They argued that cardiac PET/CT is accepted by medical associations and covered by CMS and other major payors.

• Echocardiographer Radiation Risk: A recent JAMA study suggests interventional echocardiographers face more head-level radiation exposure during heart disease interventions than the cardiologists performing the procedure. After measuring exposure during 30 transcatheter edge-to-edge mitral valve repair (TEER) and 30 left atrial appendage occlusion (LAAO) procedures, researchers determined that echocardiographers received ~5 times more radiation overall than the cardiologists (10.6µSv vs. 2.1µSv).

• Movn Series A Funding: Virtual and remote cardiac rehab company Moving Analytics (Movn) secured $20M in Series A funding (total funding now $30M). The Irvine-based company provides patients with a cellular-enabled scale, an AHA handbook, exercise bands, a blood pressure cuff, and a fitness tracker. Armed with fresh funding, Movn plans to expand its coverage, hire new staff, and begin implementing bilingual services to better serve marginalized communities.

• New Rural Provider Type: In the wake of record closures of rural hospitals, CMS released the conditions of participation for the new Rural Emergency Hospital (REH) provider type that would enable them to participate in Medicare and Medicaid programs. The proposed rule requires REHs to provide emergency, laboratory, and radiologic services to meet the needs of patients in a manner consistent with Critical Access Hospitals but adds more flexibility to staffing and outpatient service requirements to preserve access to care in rural communities.

• CTA & TAVR: Germany-based researchers found that coronary CTA-derived LV long axis shortening predicted mortality after TAVR procedures in patients with severe aortic stenosis. Using CCTA images from 175 patients, researchers determined that LV-LAS independently predicted mortality (hazard ratio: 2.83) and improved the STS-PROM score’s predictive power. The trend persisted in the sub-analysis of patients with normal LVEF (HR: 3.98). 

• CardiaTec Funding: CardiaTec, a University of Cambridge spin-out developing a cardiovascular disease drug discovery platform, recently closed a €1.6M pre-seed funding round. The company aims to use AI, biological modeling, and multi-omics cardiovascular data to identify, characterize, and evaluate potential drug targets and treatments.  

• Reduced Statin Eligibility: Danish researchers revealed that the 2021 European Society of Cardiology guidelines dramatically reduced statin therapy eligibility for primary prevention of atherosclerotic cardiovascular disease. While the new policies improved ‘discriminatory performance’ for ASCVD events, the new risk thresholds dramatically reduced class I statin eligibility to only 4% (vs. 20% – 34% in other guidelines) and essentially eliminated statin indication in women. 

• Support for CVD Startups: Novartis Pharmaceuticals UK announced a new partnership with Medtronic to support digital cardiovascular disease startups, combining Novartis’s drug development expertise with Medtronic’s global telehealth experience. The program, dubbed Novartis Biome UK Heart Health Catalyst, is currently taking applications from CVD startups, who could receive up to £3M.

Lighting New Population Health Pathways

See how Nanox AI’s population health solutions are helping health systems and payers to improve the quality and cost of care through early disease detection.

A New Standard of Heart Care

Open to a more personalized and proactive approach to cardiovascular care? Check out this video detailing Cleerly’s unique approach to heart disease risk assessments and care.