Month: January 2025

Cardiovascular Disease and Deaths On the Rise

Posted on by Viktor Zarev

Another year, another AHA report reasserting heart disease’s dominance as the number one killer in the United States, and the latest data shows that this trend is still gaining momentum.

  • Every year, the AHA reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors.
  • In 2010, the AHA released a 2020 goal to improve the CV health of all Americans by 20%, while reducing CVD and stroke deaths by 20%.

Four years after that goal’s due date, the burden of CVD in the U.S. is at an all time high, with 942k cardiovascular disease-related deaths in 2022, up by 10k from 2021.

  • Nearly half of all Americans over 20 (48.6% as of 2020) have some form of CVD (comprising CHD, HF, stroke, and hypertension).
  • Excluding hypertension (CHD, HF, and stroke only), just 9.9% of U.S. adults have CVD.

What’s causing this high CVD prevalence? While there’s no one answer for a specific patient group, the AHA’s biggest CVD risk culprits should be pretty familiar – obesity, smoking/tobacco use, and sedentary behavior.

  • From 2017 to 2020, adult obesity prevalence in the U.S. was 41.8%, while obesity-related CV deaths tripled from 1999 to 2020 (2.2 to 6.6 deaths per 100k people).
  • Sedentary behavior is also on the rise in America, with self-reported daily sitting times increasing from 332 min/day in 2007 to 351 min/day in 2017.
  • The percentage of U.S. adult smokers is now down to 11.5% (it was 51% of men in 1965), although smokers still face a nearly three-fold higher all-cause mortality risk (HR: 2.80).

However, there’s light at the end of the cardiovascular tunnel thanks to advancements in drugs like GLP-1s and new cholesterol controls, which mean heart disease isn’t a death sentence like it used to be.

The Takeaway

The AHA’s latest report reads more like a public health problem than a cardiology one, suggesting that prevention could have a greater impact than any drug, device, or treatment.

Why Mechanical AVR Valves Still Matter

Posted on by Viktor Zarev

A presentation at this year’s Society of Thoracic Surgeons (STS) conference suggests mechanical valves might lead to better survival compared to bioprosthetic valves in patients aged 60 or younger undergoing SAVR even though it seems like they’re going out of style.

  • Mechanical SAVR valves have been around in one form or another since the 1960s, but have fallen out of favor in recent years.
  • Previous analyses suggested mechanical valves have advantages over tissue valves in middle-aged patients, but lifelong anticoagulation requirements makes them a hard sell. 

Researchers examined STS registry data on ~109k patients ages 40 to 75 years who received isolated bioprosthetic (94k) or mechanical (15k) AVR over 11 years and found that mechanical valve use decreased by about half (from 20% in 2008 to below 10% in 2019).

Despite the declining use of mechanical AVR, its benefits were clear over the study’s median 5.4 year follow-up, with patients aged 40-59 seeing the most significant mortality benefits.

  • Patients aged 40-49 had a 31% lower all-cause mortality risk when receiving mechanical AVR compared to bioprosthetic.
  • For patients aged 50-59, the benefit was less dramatic, but still significant coming in at a 13% lower all-cause mortality risk.

While these mortality risks might seem convincing, there are several caveats to keep in mind, including the significant differences in patient characteristics between mechanical and bioprosthetic recipients.

  • Patients receiving bioprosthetic valves tended to be older (65.2 vs 55.7 years).
  • They also often had lower BMI (31.0 vs 32.2 kg/m2).
  • Bioprosthetic patients also had higher rates of hypertension (78.7% vs 71.8%) or prior PCI (6.7 vs 3.7%).
  • However, bioprosthetic recipients had severe aortic insufficiency less often (15.3% vs 23.6%).

The study’s design also wasn’t powered to make any certain conclusions due to its reliance on registry data, meaning a randomized head-to-head trial would be needed to confirm these outcomes.

The Takeaway

When it comes to AVR, it’s pretty clear that it’s not a “one-valve fits all” type of situation, especially in the case of mechanical valves. While the data is still less-than-certain, this presentation suggests that there could be benefits to keeping mechanical AVR on the table, at least for healthier patients under 60.

Abelacimab Stops Bleeding, But Stroke Impact Uncertain

Posted on by Viktor Zarev

Anthos Therapeutics published the full results of its Phase 2 AZALEA-TIMI 71 trial for its novel Factor XI inhibitor, abelacimab, confirming the drug’s lower bleeding risks, but leaving researchers uncertain about its ability to prevent stroke in AFib patients.

  • Current guidelines recommend direct-acting oral anticoagulants (DOACs) for AFib because they reduce ischemic stroke with a lower risk of brain hemorrhage. 
  • Unfortunately, DOACs often cause gastrointestinal bleeding, which prompted the development of new stroke-prevention methods like Factor XI inhibition.
  • By inhibiting Factor XI (an anticoagulation enzyme), drugs like abelacimab potentially prevent thrombosis without increasing spontaneous bleeding risks.

To see if abelacimab was a safer alternative, researchers randomized 1,287 AFib patients at risk of stroke to receive abelacimab (either 150mg or 90mg) or rivaroxaban (20mg), and indeed found that abelacimab treatment substantially reduced bleeding during a 2.1 year follow-up.

  • Abelacimab 150mg led to a 62% reduction in major or clinically relevant bleeding and an 89% reduction in gastrointestinal bleeding compared to rivaroxaban.
  • This bleeding reduction was so overwhelming that IDMC stopped the whole trial after only 21 months.
  • Monthly 150mg doses of abelacimab also led to 99% inhibition of Factor XI that was sustained over 2 years.

While abelacimab aced its primary outcome, and AZALEA-TIMI 71 wasn’t designed for evaluating clinical efficacy, its exploratory endpoints didn’t show stroke advantages versus DOACs.

  • Both abelacimab 150mg and 90mg led to higher incidence rates of stroke than rivaroxaban (1.21 & 1.36 per 100 person-years vs. 0.83). 
  • Abelacimab’s ischemic stroke incidence rates were similar (1.21 & 1.24), far higher than rivaroxaban’s rate of 0.59 per 100 person-year.

However, lingering questions about abelacimab’s stroke impact should be clarified by the LILAC Phase 3 study, which launched in 2023 and is designed to further explore abelacimab’s clinical efficacy.

These early glimpses into abelacimab’s stroke prevention aren’t unique, with both Bayer and Bristol Myers-Squibb running into similar study issues for their Factor XI inhibitors.

  • Bayer terminated its OCEANIC-AF trial for its Factor XI inhibitor, asundexian, due to 3X greater stroke (1.3% vs. 0.4%) and 4X ischemic stroke rates (csHR = 4.06).
  • Results from BMS’ AXIOMATIC-SSP study found that its factor XI inhibitor, milvexian, failed to meaningfully reduce ischemic stroke. 

The Takeaway

AZALEA-TIMI 71 provides incredibly strong evidence that Athos’ abelacimab reduces bleeding risks (the study’s primary endpoint), but we’ll need to see the results of the LILAC study before drawing conclusions on stroke prevention. Ultimately, without strong stroke results in future studies, abelacimab and other factor XI inhibitors may struggle to replace DOACs.

The Potential Risks of GLP-1s

Posted on by Viktor Zarev

Although GLP-1s have proven to significantly help with weight loss and cardiometabolic disorders, a new Nature Medicine study shed light on the drugs’ potential side-effects.

  • GLP-1s have skyrocketed in popularity due to their weight loss impact, while their potential heart benefits could make GLP-1s a common cardiology drug.
  • However, little is known about the long-term risks of this “wonder drug” class due to its relatively short time on the market and a lack of studies on the topic.

To tackle this problem, researchers compared Veteran’s Affairs data on 2 million T2D patients (2017-2023) taking either GLP-1s, DPP4is, SGLT2is, or usual care antihyperglycemics over a 3.68 year follow-up.

Starting with the good news, GLP-1s lowered risks for 42 health outcomes while increasing risks for 19 outcomes.

  • As expected, GLP-1s reduced MI risk by 9%, cardiac arrest by 22%, incident HF by 11%, ischemic stroke by 7%, and hemorrhagic stroke by 14%.
  • GLP-1s also led to an 8% lower risk of dementia and 12% lower risk of Alzheimer’s disease.

The less good news? There’s still no free lunch in healthcare.

  • The risk of GERD, gastritis, noninfectious gastroenteritis, gastroparesis, diverticulosis, and diverticulitis all increased with GLP-1s.
  • Other risks like hypotension, syncope, and nephritis also increased, as well as a 2.46X higher risk for drug-induced acute pancreatitis.

On the clinical side, these outcomes can help physicians make more personalized patient treatment decisions, as the researchers pointed out “people without diabetes and obesity likely wouldn’t experience many of these benefits.”

  • It’s also worth noting that the data came from military veterans who were older and mainly white, so the outcomes might not apply to other populations.

The Takeaway

Bearing in mind the current benefits of GLP-1s, it’s not likely that the side-effects examined by this study will slow down the pace of adoption. That said, it could serve as an early look into the long-term health outcomes of using GLP-1s to treat obesity and T2D.

The Finer Points of FINEARTS-HF

Posted on by Viktor Zarev

Bayer’s FINEARTS-HF study revealed that finerenone could be poised to become the next big heart failure treatment at ESC 2024, and a new series of JACC sub-studies just further strengthened its case.

  • FINEARTS-HF explored the effects of finerenone in ~6k HFmrEF/HFpEF patients and found that the drug significantly reduced worsening HF events and CV death versus placebo.
  • Finerenone (Bayer’s Kerendia) got its start with CKD, and is the first mineralocorticoid receptor antagonist to be used for HF.

The first of the featured studies revealed that patients treated soon after experiencing a worsening heart failure (WHF) event saw greater benefits.

  • Finerenone lowered the risk of CV events most in patients enrolled within one week (RR: 0.74) or three months of WHF (RR: 0.79).

The second sub-study discovered that finerenone reduced HF events and improved patient health, regardless of baseline KCCQ score.

  • Finerenone reduced the risk of CV death and WHF events across all KCCQ ranges from scores of 0-<57 (RR: 0.82), to 57-<81 (0.88), and 81-100 (0.88). 
  • The drug also significantly improved KCCQ from baseline by an average of 1.62 points at 12 months.

Finerenone proved effective regardless of baseline bodyweight, reducing CV death and WHF events across all BMI groups (underweight/normal, rate ratio: 0.80; overweight: 0.91; obesity class I: 0.92; obesity class II-III: 0.67).

Despite the strong benefits, finerenone was not without its side effects, as the fourth and fifth sub-studies found that the drug led to a mild initial decline in eGFR, although it wasn’t significant enough to warrant stopping treatment. 

  • Nearly a quarter of finerenone patients experienced a ≥15% decline in eGFR compared to 13.4% on placebo. 
  • Notably, eGFR decline was associated with higher risk of CV death and HF events in patients on placebo but not in those on finerenone (aRR: 1.07 vs. 1.50). 

The Takeaway

After an impressive primary study and several supportive sub-studies, all signs seem to be pointing in the direction of finerenone as a frontline HF treatment. That’s pretty big considering how relatively empty the HF pharmaceutical space was a decade ago.

AI-CCTA Beats SPECT, Again

Posted on by Viktor Zarev

A recent study out of UCLA seemed to add to the body of evidence supporting AI-assisted CCTA as an alternative to SPECT for diagnosing obstructive coronary artery disease, although holes in the study suggest that CCTA AI has more to prove

  • SPECT continues to be a first-line test to diagnose coronary ischemia, often instead of or before invasive coronary angiography.
  • However, SPECT’s cost, necessary radiotracers, lower image quality, and radiation exposure have raised doubts about its continued dominance.

To determine if AI-CCTA could hold its own, researchers analyzed CCTA images from 175 patients using Cleerly’s AI-QCT ISCHEMIA model and found it outperformed SPECT when compared to invasive angiography.

  • AI-CCTA showed a sensitivity of 75% and specificity of 70% for predicting coronary ischemia, outperforming SPECT (70% & 53%).
  • AI-enhanced CCTA also surpassed SPECT’s negative predictive value among female patients (91% vs. 68%).
  • However, AI-CCTA’s AUCs were only slightly higher than SPECT (0.81 vs. 0.76).

One important caveat is how the researchers reached these results, as one of our readers pointed out that “coronary angiography was used as the gold standard for comparison” but only 16 patients in the study received ICA.

  • As a result, comparative analysis would only be based on those 16 patients.
  • Yet, the study reports sample sizes of 17 and 25 for sensitivity and specificity, and also varied on the NPV endpoint.
  • This led to all of the proportions reported not matching the study’s final sensitivity and specificity results.

Even though the study misses the mark and AI is still somewhat unproven, AI-CCTA has been gaining momentum versus SPECT in recent years. 

  • CCTA’s biggest step forward was the 2021 AHA/ACC chest pain guidelines that established it as a front-line coronary artery disease test, potentially instead of SPECT.
  • Then a JACC study from 2023 found that AI-ISCHEMIA was superior to SPECT and similar to PET and FFRCT in ischemia prediction (AUCs: 0.91 vs. 0.71).
  • Another 2024 JACC study found the AI-ISCHEMIA + CCTA approach more accurately diagnoses coronary ischemia (AUCs: 0.80 vs. 0.72).

The Takeaway

AI assisted CCTA is still relatively new and in some ways unproven, but its growing usage, new reimbursements, cost-effectiveness, and greater accuracy are worth keeping in mind as the modality matures in comparison to more established scans like SPECT. However, it will take stronger results than this study in order to drive a more meaningful shift in exam volumes.

AI-ECG’s 2025 Kickoff

Posted on by Viktor Zarev

The buzz around artificial intelligence’s impact on cardiology keeps growing louder, and that’s proving to be particularly true in the AI-ECG segment, with 2025 already off to a strong start from ECG startups and researchers alike.

  • AI and ECG pair well due to the strong pattern recognition that machine learning algorithms can achieve.
  • This AI-ECG pairing is bringing the modality into a wider range of diseases and allowing integration with new device form factors.

One pertinent example is AccurKardia’s recent FDA breakthrough designation for its ECG-based, AI-powered AK+ Guard hyperkalemia detection software. 

  • AK+ Guard uses Lead I ECG data to alert patients and clinicians of moderate to severe episodes of excess blood potassium (hyperkalemia) that can lead to sudden cardiac arrest.
  • Accurkardia designed AK+ Guard for consumer and clinical wearables to support remote hyperkalemia monitoring for patients with renal disease, CKD, and other risk factors.
  • For reference, 37M people in the U.S. suffer from CKD, and hyperkalemia is associated with a 16.6% higher mortality rate in those patients.

Tackling another CV complication, researchers developed an AI-ECG risk estimator for hypertension (AIRE-HTN) that could become a useful tool for predicting future CV events. 

  • AIRE-HTN was trained on ~190k patients at Beth Israel Deaconess and validated on 65k patients from UK Biobank.
  • Ultimately, the study found that patient AIRE scores accurately predicted CV death (HR: 2.24), HF risk (HR: 2.60), MI (HR: 3.13), ischemic stroke (HR: 1.23), and CKD (HR: 1.89) compared to traditional risk factors.

The commercial side of the AI-ECG arena is similarly heating up, including a new partnership between AliveCor and ECG AI developer Anumana.

  • The partnership will focus on AliveCor’s Kardia ECG devices and Anumana’s ECG-AI algorithms, and apparently includes both AI development and integration.
  • Their first target will be Anumana’s ECG-AI algorithm, which detects low ejection fraction using 12-lead ECG data, and recently landed CMS reimbursement.

The Takeaway

Though there’s no shortage of AI skeptics in healthcare, it’s becoming clear that AI is bringing ECG into new disease areas and form factors. For a modality as established as ECG, that’s a big deal, and it could have a major impact on both disease detection and patient access.

Cardiologists Busted for Overbilling Nationwide

Posted on by Viktor Zarev

Adding to a relentless trend of Medicare schemes, 16 cardiology practices agreed to pay more than $17.7M to resolve allegations that they overbilled for diagnostic radiopharmaceuticals and violated the False Claims Act.

  • In 13 states and D.C., Medicare Part B reimburses providers for radiopharmaceuticals based on self-reported acquisition costs, leaving billing up to the honor system.
  • This structure was abused in 12 of these 13 states, highlighting the pervasiveness of cardiac radiopharmaceutical overbilling.

The DOJ accused these practices of reporting “inflated acquisition costs” to Medicare for materials needed to perform cardiovascular imaging.

  • Radiopharmaceuticals like sestamibi and tetrofosmin, which are used for cardiac SPECT scans, made up the bulk of overbilling.
  • The questionable conduct occurred for at least a year, and in some cases for more than 10 years.

The three largest settlements accounted for nearly two thirds ($11.7M) of the total payment, covering restitution, fines, and accrued interest.

  • Western Kentucky Heart & Lung Associates came in first, paying a whopping $6.75M.
  • Heart Clinic of Paris paid $2.6M.
  • Scranton Cardiovascular Physician Services paid $2.3M.
  • Meanwhile, some practices paid as little as $50k to $160k.
  • The whistleblowers will make off with $2.7M of the settlement money.

Although the settlements don’t represent an admission of guilt from the practices, they are part of a larger trend of Medicare overbilling that has plagued the U.S. healthcare system. That’s certainly been true within cardiology over the last year.

  • Cardiac surgeons at Baylor St. Luke’s fraudulently billed for over 5,000 concurrent surgeries while using residents to perform the procedures.
  • Cape Cod Hospital paid an eyewatering $24.3M to resolve billing allegations for pre-TAVR evaluations that didn’t meet requirements.
  • An NJ cardiologist submitted $1.9M worth of false claims for office visits that either never happened or were shorter than claimed.
  • Cardiac Imaging of Illinois was charged for a kickback scheme that paid referring cardiologists as if they were supervising PET scans when they weren’t.

The Takeaway

While overbilling continues to find new ways to creep into the U.S. healthcare system, the bigger issue is the inevitable strain it puts on Medicare’s ability to help the patients who are actually sick, which begs the question: what will it take for us to stop robbing Peter to pay Paul?

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