Month: November 2023

The 35 Best Cardiology Newsletters, Websites, and Influencers to Follow

Posted on by Jake Fishman

We’re dedicating today’s top story to the people and publications that we rely on to find the most interesting cardiology stories from across the web. Assuming that you already subscribe to Cardiac Wire, these are the 35 other newsletters, websites, and social media accounts to follow if you really want to know what’s happening in cardiology.

I’ll always check the mainstream cardiology news websites (TCTMD, Medscape, et al.) and the major cardiovascular journals (JACC, AHA, JAMA Cardiology, etc.), but in order to find news that you won’t see elsewhere and understand how it impacts care, the juiciest stories usually come from the newsletters and websites run by people of cardiology.

The Best Cardiology Social Media “Influencers” to Follow

Nowadays the juiciest news isn’t even published, it’s posted. And it’s often posted by these legends of cardiology social media.

The Best Healthcare Newsletters and Sites

It can be pretty comfy inside the cardiovascular news bubble, but cardiology is just one part of healthcare. That’s what makes these newsletters and websites from outside the cardiology department so important.

The Takeaway

If you want to stay informed about cardiology news and know what’s going on across healthcare, these sources will give you everything you need. You can also join over 12k cardiology lifers and sign up for Cardiac Wire.

PS – If there’s any cardiology publications or people that should be on this list, let me know!

Bayer Halts Asundexia Factor XI Trial Due to Inefficacy

Posted on by Jake Fishman

The Factor XI inhibitor movement hit a setback last week, after Bayer announced that it halted its OCEANIC-AF trial due to asundexian’s lack of efficacy.

  • Investigative Factor XI inhibitors have sparked optimism among cardiologists for their potential to become safer antithrombotics, avoiding anticoagulants’ typical bleeding risks
  • Asundexian is Bayer’s most advanced Factor XIa inhibitor, and already gained two FDA Fast Track Designations (stroke & systemic embolism prevention in Afib patients, stroke prevention after non-cardioembolic ischemic stroke)

The phase III OCEANIC-AF trial was intended to evaluate asundexian against BMS’ popular anticoagulant apixaban (Eliquis) among 18,000 Afib patients with higher stroke risks.

  • The study was designed to measure asundexian’s effectiveness in preventing stroke or systemic embolism
  • However, an Independent Data Monitoring Committee (IDMC) recommended OCEANIC-AF’s termination just eleven months after enrollment began due to asundexian’s “inferior efficacy” versus apixaban

Bayer didn’t provide more details on the results that prompted the IDMC’s recommendation, but as one prominent cardiologist with a large public platform noted: “To have it stopped this early must have meant there was a serious signal of lack of efficacy.”

Asundexian continued to achieve the safety benefits that Factor XI inhibitors are known for, with similar bleeding reductions as the previous PACIFIC-AF trial.

Despite this setback, the IDMC still recommended that Bayer continue with its OCEANIC-STROKE phase III trial evaluating asundexian’s ability to prevent ischemic stroke in patients who previously experienced a stroke.

  • Bayer will also continue to evaluate “other indications in patients in need of antithrombotic treatment.”

There will also be more eyes on other investigative Factor XI inhibitors from Anthos Therapeutics and Janssen/Bristol Myers Squibb, noting that Anthos’s recent AZALEA-TIMI phase II trial also showed impressive bleeding reductions versus rivaroxaban, but more strokes.

The Takeaway

Some might see this as a sign that Factor XI’s “anticoagulation without bleeding risks” value proposition was too good to be true. However, it’s very possible that different Factor XI and Factor XIa inhibitors have different mechanisms, while the scientific learnings from this setback might actually lead to progress for the overall Factor XI drug class.

Medtronic’s Symplicity Spyral RDN System Lands FDA Approval

Posted on by Jake Fishman

The brand new US renal denervation arena gained its second major competitor on Friday, with the FDA approval and immediate commercial launch of Medtronic’s Symplicity Spyral RDN system.

  • Renal denervation (RDN) is intended for hypertension that can’t be controlled by conventional therapies, either due to ineffectiveness, side effects, or adherence issues
  • RDN is a minimally invasive procedure that lowers blood pressure by denervating the sympathetic nerves surrounding renal arteries, reducing overactivity that can lead to hypertension
  • Medtronic’s Symplicity Spyral RDN system has been in development for 14 years, and is already approved in over 70 countries globally

The Symplicity Spyral’s approval comes just 10 days after Recor Medical’s Paradise system became the first RDN system to land FDA approval, suddenly introducing two RDN systems to US clinicians and patients who were limited to pharma and lifestyle interventions before now.

The approval also represents somewhat of a comeback story, after an FDA expert panel voted against the Symplicity Spyral in August, finding that its benefits didn’t outweigh its risks (6-7 vote).

  • Recor’s RDN system on the other hand, came away with a panel endorsement through a far stronger 10-to-2 vote

It’s possible that the Symplicity Spyral’s approval was helped by an updated FDA indication, positioning it as an “adjunctive treatment (aka additional treatment) in patients with hypertension in whom lifestyle modifications and antihypertensive medications do not adequately control blood pressure.”

  • That’s the same FDA indication as the Recor Paradise system, but represents a change from Medtronic’s PMA application which didn’t limit the Symplicity Spyral to patients also taking antihypertensives (not just for adjunctive use).

With the Symplicity Spyral’s approval now complete, eyes will be on Medtronic’s powerful commercial organization to see how they can bring RDN into clinical practice, noting the many hurdles that completely new interventions usually face when targeting a disease that’s historically been treated with medications.

Takeaway

Although media coverage might focus on the Spyral Symplicity’s negative panel vote, that will only matter if it doesn’t prove effective in the clinic or for Medtronic’s business.

What might not get enough coverage is how much of a monumental feat this is for the Medtronic RDN team, and what the sudden availability of two different renal denervation systems might mean for hypertension treatment in the US. 

If renal denervation ends up achieving what Medtronic and Recor believe it’s capable of, we just entered a completely new era in hypertension treatment.

Cardiac Wire’s Top Six Takeaways from AHA 2023

Posted on by Jake Fishman

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.

Lilly’s Zepbound (aka tirzepatide) Lands FDA Approval for Weight Loss

Posted on by Jake Fishman

The US obesity management arena gained a major new competitor last week with the FDA approval of Eli Lilly’s Zepbound, giving obese and overweight patients in the US a second (on-label) option beyond Novo Nordisk’s Wegovy.

  • Zepbound is Lilly’s new obesity-targeted brand for tirzepatide, which has been available to US diabetic patients under its Mounjaro brand since May 2022
  • Although often referred to as a GLP-1, tirzepatide uniquely activates both GIP (affects adipose tissue regulation and storage) and GLP-1 (increases feeling of fullness and decreases gastric emptying) hormone receptors

Zepbound already has significant momentum, given the massive popularity of GLP-1s, the fact that many people were already using Mounjaro as an off-label weight loss treatment, and tirzepatide’s impressive weight loss achievements in recent studies:

  • Lilly’s SURMOUNT-3 and SURMOUNT-4 trials showed that tirzepatide allows overweight people who don’t have type 2 diabetes to shed a massive 26% of their weight
  • Before that, tirzepatide drove 13.4% to 15.7% weight reductions among people with T2D in the SURMOUNT-2 trial, and 15% to 20.9% reductions in non-diabetic adults in SURMOUNT-1
  • Like all GLP-1s (so far), tirzepatide also comes with a risk of adverse GI events

Those weight loss results should make Zepbound a formidable opponent to Novo Nordisk’s Wegovy, which might have a first-to-market advantage, but only achieved 10.9% to 14.9% weight reductions in previous trials.

Zepbound’s launch could also improve patient access to GLP-1s, potentially alleviating shortages, and creating more price flexibility.

  • Lilly executives were sure to point out that Zepbound’s $1,059 monthly price is 20% lower than their “lowest competitor,” and highlighted new programs that can reduce Zepbound to between $25 and $550 per month with commercial coverage 
  • Time will tell if increased competition drives down prices further, or increased adoption drives expanded payor coverage

Particularly notable to CW readers, tirzepatide has also been shown to positively impact key cardiovascular metrics, including cholesterol and blood pressure. 

  • However, its cardiovascular impact might prove to be much greater in the future, given that it’s currently being evaluated in a range of cardiovascular-related studies (MACE, CKD, and HFpEF).
  • One more reason for cardiovascular optimism: Novo Nordisk’s semaglutide was recently shown to reduce major cardiovascular events by a whopping 20% over five years.

The Takeaway

There’s arguably no pharma segment with stronger patient demand than GLP-1s, and Zepbound’s weight loss and cost advantages just made that segment even hotter.

Recor Medical’s Paradise Renal Denervation System Lands FDA Approval

Posted on by Jake Fishman

The renal denervation race hit a major new milestone this week after Recor Medical’s Paradise system became the first to land FDA approval.

  • Renal denervation (RDN) is intended for hypertension that can’t be controlled by conventional therapies, either due to ineffectiveness, side effects, or adherence issues
  • RDN lowers blood pressure by denervating the sympathetic nerves surrounding renal arteries, reducing overactivity that can lead to hypertension
  • Recor’s ultrasound-based Paradise System has been in development for 14 years, and gained European approval all the way back in 2012

Some might have seen this approval coming after an FDA expert panel endorsed the Paradise System in August, voting 10-to-2 that its benefits outweigh its risks.

  • That was a far stronger result than Medtronic’s RDN system, which fell short with a 6-to-7 vote, but is still seen by some as on a path towards FDA approval.

The Paradise System’s FDA approval and panel endorsement were supported by Recor’s pivotal RADIANCE II trial, which found that the RDN system met both primary safety and effectiveness endpoints without any major adverse events.

  • In fact, all three of Recor’s sham-controlled RADIANCE RCTs have met their safety and efficacy endpoints, including two off-medication trials that achieved a -4.5 mmHg average BP reduction.

Being first to market comes with obvious advantages, but online and conference chatter suggests that the Paradise System (and RDN in general) will face its share of post-approval challenges:

  • Earning physicians’ trust in its impact and durability, and their confidence in identifying patients who are most likely to respond to RDN
  • Overcoming physicians’ pharmaceutical-focused approach to hypertension
  • Achieving reimbursements and a spot in clinical workflows

The Takeaway

The staggering number of Americans living with uncontrolled hypertension and the clinicians who care for them now have a new tool to help bring their blood pressure under control. That could be huge for these millions of patients, and for Recor Medical, which is now the clear frontrunner in what might prove to be a multi-billion dollar market.

America’s Cholesterol Awareness Problem

Posted on by Jake Fishman

The prevalence of US adults with high LDL cholesterol levels, and the prevalence of adults who are unaware of their high LDL-C are both declining. However, these improvements aren’t happening nearly fast enough – especially given our expanding cholesterol treatment options.

That’s the takeaway from a new JAMA Cardiology Research Letter analyzing National Health and Nutrition Examination Survey data from 23,667 US adults from the National Health and Nutrition Examination Survey between 1999 and 2020.

Overall, 1851 (7.8%) of the participants had LDL-C levels of 160-189 mg/dL, while 669 (2.8%) had LDL-C levels of 190 mg/dL or greater. Those overall numbers reflect significant age-adjusted declines between the 1999-2000 and 2017-2020 study periods:

  • The prevalence of participants with 160-189 mg/dL LDL-C levels fell from 12.4% to 6.1%, representing a decline from 21.5M to 14M US adults
  • The prevalence of participants with 190 mg/dL or greater LDL-C levels fell from 3.8% to 2.1%, representing a decline from 6.6M to 4.8 US adults

That period also drove notable declines in Americans who were unaware of their high cholesterol and not receiving treatment.

  • The prevalence of unaware/untreated participants with 160-189 mg/dL LDL-C levels fell from 52.1% to 42.7%, representing a decline from 11.9M to 6.1M US adults
  • The prevalence of unaware/untreated participants with 190 mg/dL or greater LDL-C levels fell from 40.8% to 26.8%, representing a decline from 3M to 1.4M US adults

At first glance, these cholesterol declines and awareness improvements seem like a public health success story, however the authors were more focused on the 7.5M million Americans with high cholesterol who remain unaware and untreated

These cholesterol awareness and treatment gaps are (unsurprisingly) deepest among Black, Hispanic, and socioeconomically disadvantaged people, as well as among younger people who would benefit most from early treatment. 

  • These disparities are likely due to challenges with access to primary care, low rates of screening in primary care, lack of consensus on screening recommendations, insufficient emphasis on LDL-C as a quality measure, and hesitance to treat asymptomatic individuals. 

The Takeaway

Cholesterol awareness and treatment rates might be improving, but they’re still “suboptimal,” and they highlight America’s continued challenges with LDL-C education, screening, and action.

Chinese Medicine Tongxinluo Improves STEMI Outcomes, Sparks Debates

Posted on by Jake Fishman

Could the next major heart attack treatment come from a traditional Chinese medicine? A new JAMA study suggests that might be more realistic than many of us think, after showing that the Chinese medicine Tongxinluo significantly improves outcomes among patients with acute ST-segment elevation myocardial infarction (STEMI). 

  • Tongxinluo has been cleared in China to treat angina and stroke since 1996, and has shown to have cardioprotective effects in over a dozen previous clinical studies
  • It also has a list of ingredients that’s sure to raise Western eyebrows (plants, cockroach, scorpion, cicada, centipede, leech)

CTS-AMI trial researchers randomized 3,777 patients from 124 hospitals in China to take either Tongxinluo or a placebo within 24 hours of STEMI, and then receive guideline-directed treatments (antiplatelet therapy and coronary reperfusion) for one year.

As you might have guessed, the results were far stronger in the Tongxinluo group.

  • MACCE at 30 days (3.4% vs. 5.2%)
  • Cardiac death at 30 days (3.0% vs 4.2%)
  • Myocardial reinfarction at 30 days (0% vs 0.5%)
  • MACCE at 1 year (5.3% vs 8.3%)
  • Cardiac death 1 year (4.5% vs. 6.1%)
  • All cause death at 1 year (5.1% vs. 6.6%)

The Tongxinluo group did have more adverse drug reactions than placebo-takers (2.1% vs 1.1%), largely due to GI issues like stomach discomfort and nausea.

The Tongxinluo group’s 36% lower MACCE rate is quite remarkable, avoiding one major adverse event for every 55 patients who took it, which is even below alirocumab’s “number needed to treat” of 62.

However, the CTS-AMI study generated far more pushback than we typically see when a drug shows these types of improvements in a double-blind RCT.

  • An accompanying JAMA editorial expressed doubts about whether these results could be repeated outside of China given genetic, diet, and health differences, while emphasizing that Tongxinluo’s mechanisms are unknown. 
  • An Editor’s Note discussed the challenges JAMA faced when deciding whether to even publish this study, given that none of Tongxinluo’s ingredients are known to benefit STEMI patients.
  • Other online comments suggested that the Chinese government pressures researchers to show positive results in traditional Chinese medicine studies. 

The loudest proponent of the CTS-AMI trial ended up being John Mandrola, MD, who suggested that this might be “selective skepticism” given the trial’s solid design and outcomes, and considering that we don’t understand the mechanisms behind a number of major Western cardiovascular pharmaceuticals without similar concerns.

The Takeaway

Tongxinluo has been approved to treat angina and stroke patients in China for over 26 years, and based on the results of the CTS-AMI trial it might also reduce post-STEMI events by a very significant 36%. 

However, responses to this study suggest that Western clinicians and scientists will need a lot more evidence that Tongxinluo (and its individual ingredients) actually improve MI outcomes before they’re ready to accept it. It is made out of centipedes after all…

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