Feb 13 2026 This Week in Cardiology

You're listening to This Week in Cardiology from dot org Medscape. Any views expressed are the presentation. And do not necessarily Hi everyone, this is John Mandrola from the Heart.org Medscape Cardiology, and this is This Week in Cardiology for February 14th, 2026. This week, Ticagulor versus Prosagrel, a new left atrial appendage closure device. PFAAF ablation results, lifestyle intervention in AFib, the term provider versus doctor, and coffee.

I'll start with the Tuxedo II trial. JAMOCARY has published Tuxedo II, trial of Ticagular versus Prosagrel as the second antiplatelet drug with aspirin after coronary stenting in patients who have diabetes and multivessal disease. Now one twist on the RCT of eighteen hundred patients was that it was done in India. Now as a neutral Martian, I like to study question because I see much more Ticagulor loose use than Prosagrel.

But the German government funded ISAR React V trial was highly significant thirty six percent higher rate of death MI and stroke with Ticagulor versus Prosagrill. that trial was published in twenty nineteen, now seven years ago. Of course, I get the fact that it's more complex logistics to give with Prosagrill, but gee whiz, as I have said many times, It shocks me that Ticagular use is so much greater than Prosagrill.

Now, but that's not the only knock on Tychagulor, right? In Plato, which was Tychagulor versus Clopidogrill, the top line was that Tychagulor reduced the primary endpoint of CV death MI and stroke by 16%. But the Play Doh trial has legendary criticisms and weaknesses, right? In US patients there were more deaths in the Tychagular group compared to Clopidogril, the opposite of what was seen globally.

This striking regional difference led to AstraZeneca's first FDA application being rejected and raised fundamental questions about the drug's efficacy. Second Plato problem Four countries Israel, US, Georgia and Russia, were monitored by independent contract research organizations rather than by AstraZeneca.

All four independently monitored countries showed numerically higher rates of the primary outcome in the Ticagular group compared to Clopidogril. Third problem. There were also discrepancies between death reports submitted to the FDA, 938 deaths, Versus those provided to trial investigators, 905 deaths. Now some death causes were reclassified in ways that favored Tychagulor.

Clopidogal deaths switched from non vascular to vascular while some ticagular vascular deaths were switched to non vascular or unknown. Fourth problem with Play-Doh, the unprecedented all-cause mortality reduction, hazard ratio zero point. Seven eight or hundred and seven more lives saved was so large it prompted an editorial titled Do You Believe in Magic?

Because this benefit exceeded what had been seen when comparing active drugs to placebo in similar trials and seems biologically implausible. Final problem with Plato, Thomas Marciniac, an FDA reviewer. identified a fundamental paradox. If Tychagulor provided superior platelet inhibition, patients undergoing early PCI should have benefited most, but they actually fared worse in the short term compared to Clobitogral patients. Contradicting the drug's supposed mechanism of action.

Now, my point is that Tychagulor really didn't look much better than Clopidogril and was clearly worse than Prosagril in the ISAR React V trial. Now we go to the tuxedo trial. This was a study with all comers for stents. 60% had MI, 21% unstable angina, and 20% with chronic coronary syndrome. Okay, the main results at one year the primary endpoint of death MY stroke or bleeding occurred in sixteen point six percent taking tychygular versus fourteen point two percent taking Prosagrill.

The risk difference of two point three percentage points worse with Ticagulore failed to meet the prespecified threshold for non inferiority. Both the MACE endpoints, a composite of death MI stroke was

higher with ticagular, 10.4 versus 8.6%. And also major bleeding was higher, 8.4% versus 7.14% with Ticagular compared with Prosagrill. And the authors concluded that, quote, In patients with diabetes and multivessal disease undergoing PCI, Tychagular was not non-inferior to prostagrel for the reduction of the primary outcome at one year follow-up.

Now my comments. I've asked colleagues why they favor Ticagular or Vaprosagrel and what I usually get are fairly weak answers. It's often about logistics. Now you may not want to speculate, but as a cardiologist who does not do stents, I cannot understand why Ticagulor is so dominant over Prosagrill in US markets. And when Plato was so flawed an Isau react clearly showed Prosagrel's superiority. What is it that makes Ticagular so sticky despite the empirical evidence?

I can't know for sure, but there are potential reasons. Uh here's what I could think of. Ticagulor had the first mover advantage. That seems like a weak argument because the Bigotran had the first mover in oral anticoagulants, but has been crushed by a pixeban and riveroxaban. Tacagular, of course, had marketing and messaging. In fact, a twice daily dosing, which is clearly inferior, was positioned as quote more consistent coverage.

They had a guidelines initial inertia, right? So once Tychagular was embedded in the guidelines as a class one recommendation, uh, it was hard to change. Uh there's course issues with hospital formulary lock in. Once hospitals negotiate contracts and build protocols, there's no Can become resistance to change. There's the issue of cognitive biases, right? So cardiologists who adopted Ticagulor early maybe became invested in the decision.

There's always a status quo bias and in in meaning that if something is working and patients do fine, it's continu it's continued. The main quibble I have with tuxedo though is the choice to do non-inferiority design. Non-inferiority design means that the new treatment should have some advantage, right? Less costly, less invasive, less burdensome. Uh I don't really see tychacular would justify a non-inferiority trial.

The PI, Professor Bangalore, wrote to me that the hypothesis started after I saw React V, where there was a diabetic subgroup, and that in that subgroup it seemed to be similar outcomes between Tychagulor and Prosygrill. Nonetheless, the results are clear. The mace outcomes were better on Prosygroil, bleeding was lower on Prosagral. I wonder what a meta analysis of trials would look like. To me, Prosagil looks to be the better drug when doctors feel they need more than clopitogril.

Ticagular stickiness despite the evidence is a worthy study for students of evidence-based medicine. It's just something curious to think about.

All right, next topic is the Veritas study of a dual-sealing left atrial appendage closure device.

Jackie P has published results of the Veritas study of a left atrial appendage closure with a newer generation dual-seal occluder made by Abbott. But before I tell you about this single-arm study of 400 patients, we should mention the irony of calling anything in this space by the Latin word for truth I say that because the seminal regulatory trial prevail missed making non-inferiority and its first co-primary endpoint of stroke, systemic embolism, and CV death against Warthrin.

I'm not going to go into that whole thing again. Let's not relitigate that. Left atrial appendage closure, like any procedure, is going to iterate. This is a good thing. Procedures iterate and they usually get better. then the proponents of appendage closure will argue that engineering and technology are going to improve closure rates, and if you do that you should improve outcomes.

Now I don't doubt the former, it's going to improve, but I highly doubt that that we're going to have better outcomes. Now, the Abbott bioengineers have come up with a next generation amulet device. The study was designed to assess 45-day safety and performance outcomes. It's a single arm study, though they screened 650 patients to include 400 patients, and that's sort of important because one in three patients were excluded.

The implant success rate was very high, near one hundred percent. Procedure time was short. Uh two thirds of the patients were in sinus rhythm, one third were in AFib, and I want to just Pause there. This is strange because if two-thirds were in sinus rhythm, they must have had PAF. Paroxysmoleph.

So if they have paroxysmal AFib, I'm wondering why weren't they ablated to get rid of the AFib? And then if you get rid of the AFib, there's two trials showing that it's reasonable to stop anticoagulation, and then you don't have to have a foreign body in your heart. Now the main findings were that device related thrombus was found in two point four percent of patients, major bleeding in three point three percent, any periodice leak small

uh including were six percent. There were two pericardial effusions in four hundred patients that required drainage, and twenty-four of four hundred patients did not have an adequate TEE for assessment. The authors and editorialists called these results quote promising. Now, while they were clearly better than previous amulet data, I'm not sure that they are all that promising, right? If you have device related thrombus, y it's a failure, an utter failure, because it quadruples stroke risk.

and it requires oral anticoagulation, which is uh the point of the procedure to avoid oral anticoagulation. So two point four percent to me is a lot of device related thromus, given that only super expert implanters participate in this study. So a 2.4% DRT rate would likely be much worse in less experienced hands. Also, a peri device leak rate of 6% is less than ideal. And this was with TEE. We know that if CT had been used, the peridive leak would likely be higher.

Now the proponents will say they're small leaks, and I say, okay, small leaks are better than large leaks, but even small leaks increase the risk of stroke. And then there's the business 3.3% had major bleeds. That seems like a lot to me. How many of these patients would have had major bleeds if they went to lunch instead of having a major invasive procedure? Now 24 or 400 patients did not have a TE, so we have no results for six percent of this group, which is a lot.

In sum, I'm not as impressed by these numbers as the proponents. And again, my friends, if you think probabilistically, and this is really a probabilistic problem, right? Because Patients have to accept an upfront risk of an invasive procedure, that's X, to get a probabilistic benefit in the future. And that future benefit has to be greater than the upfront risk.

So even if you were to assume there is some future stroke benefit or bleeding reduction from this procedure, I don't believe that, but let's say there is a tiny benefit in the future, these early complications put patients in the hole probabilistically. And then this is the fatal flaw of appendage closure. If there is a two or three or four or five percent complication rate with this device,

There has to be an even greater percentage risk reduction in stroke or bleeding, and that's not been shown. So if I were at the FDA, I would not look favorably on these data. Next topic is pulse field ablation over four years.

As many of you know, I've been transformed from a PFA skeptic to PFA enthusiast. I've now done A couple hundred PFAF. And for ablation in the left atrium, PFA is really much better and amazing. It's faster, it's easier on the patient, and it's largely devoid of the esophageal disaster worries. But we should have data, and recently Nature Medicine has published four-year results of the advent RCT comparing PFA to thermal ablation.

It's an important question because until now the four RCTs of PFA versus thermal ablation had only one year follow up, and to briefly review The Advent, published in New England, PFA versus thermal ablation, no difference in efficacy. The sphere persistent AFib, published in Nature, PFA versus RF, PFA was not inferior to RF.

The single shot champion published in New England Journal was PFA was slightly better than Cryoballoon. And then just recently the beat paroxysmal Aphib published in European Heart, PFA was similar to RF. In the original advent trial, about six hundred patients were randomized. For this follow up four year study, sixty percent of the patients, about three hundred and sixty four

were re enrolled, re enrolled at least three years after their initial ablation. Of these, one hundred eighty three randomized to PFA, one hundred eighty one were randomized to thermal ablation. About half of thermal ablation was RF, the other half cryoballoon. Most patients consented to medical chart review and Holter while a handful just consented to chart review.

The baseline characteristics of these two groups were similar in the two re-enrolled groups, which is kind of important because there could be bias in patients who consented versus did not consent to more follow-up or to be re enrolled. The mean follow-up was three point six years in both groups, and the main finding was that the estimated probabilities of four year treatment success.

were seventy-three percent for PFA, 64% for thermal boblation, and although better for PFA, the p-value was 0.12. They did a time to failure analysis, and this was by Kaplan Meyer Kerr's and it demonstrated an early decline with most failures occurring within the first six months, followed by a relative plateau, and then the landmark analysis demonstrates that Only 9% of patients who were without recurrences in the first year with post-PFA will have recurrences in the four-year follow-up.

They also looked at antiarrhythmic drug use and the need for hospital based AF treatment and these were also similar between the two. Treatment strategies. Repeat ablation was slightly higher for thermal ablation, but it was close, 17% versus 10%. As for stroke outcomes, there were zero events in the thermal group and only one intracranial hemorrhage and one TIA in the PFA group.

These are extremely low stroke stroke rates or similar to the recent Ocean and Alone AF trials, and it's A good news and B The fact that stroke rates are so low after ablation argues strongly against concominant left atrial appendage closure at the time of ablation because if stroke rates are that low you can simply stop anticoagulation.

So my comments. I have to be complimentary to Vivek Reddy and his co-authors because getting longer term data on PFA is important and then this was a fair amount of work. While re-enrollment could lead to bias and that those who consent to re-enroll may be different than those who don't consent, it does seem to have been balanced in the two arms. And even with these limitations, it does seem like the results with PFA hold up.

To be sure, AF ablation remains a humbling procedure because despite 20 years of iteration, we failed to achieve success in about a third of our patients. Now the authors in the paper spent a lot of words making the case that PFA may be slightly better than RF. For instance, AF burden reduction looked a bit better. The redo rates were a little bit better with PFA, but

I don't think the differences are that great, but it also doesn't matter because PFA is faster, it's easier on patients, and you don't have to worry about the patient dying at three to four weeks from an atrial sophageal fistula. So PFA is here to stay. I can't imagine going back to doing RF uh in the left atrium for AF ablation. Now I still think there are gonna be iterations to be made in the waveforms of electrical activity during PFA.

As it's going to be iteration in catheter types and while every company makes PFA catheters, there are clearly better PFA systems in use now. I won't tell you which ones I believe are better because It's just my opinion and I don't want to get in any fight. The final thing to say about PFA, though, is that it has lowered the bar for who we take to the EP lab for ablation.

And this is both good and bad. It's good because I've done a handful of ninety year olds who are back to playing golf because of the procedure and I would have probably never done RF ablation in the ninety year old. But the fact that we've lowered our threshold is bad because AF is mostly a systemic disease.

So it's rare to have the cyclist patient who has P V driven AF who we cure with P VI. Instead the typical US patient with AF has cardiometabolic issues such as obesity, hypertension and diabetes, sleep apnea. And EP doctors are not supposed to be proceduralists. We're supposed to be doctors. And doing a 30-minute PFA ablation is not going to be enough in many of these patients who have other conditions. And also, finally, my mantra of Aethib care is to give peace a chance.

But just because we have PFA does not mean we shouldn't take the time to educate patients and adjust some of the lifestyle factors. And mainly just wait some time to see if AFib are gonna go away on their own. Taking people to the EP lab even for a PFA after one or two episodes of AFib is definitely bad medicine.

Alright, next topic is a funny topic. It's about a name. The American College of Physicians, who published the Annals of Internal Medicine, have published a policy paper describing the trends, significance, and implications for patients, physicians, and healthcare of the use of the term provider. Now this may be an American US thing, I'm not sure it comes up in other countries, but here in the US, the doctors are increasingly referred to as a provider.

Now I'm in my thirtieth year at the same hospital and I've seen the transition. When I started a hospital was run by nurses and doctors, and There were only doctors taking care of patients. There were no APRNs, there were no PAs. And at that time doctors were called doctors. But medicine has changed. Now Administrators run hospitals, and doctors are not the only humans that are doctoring patients. PAs and APRNs also provide medical care to patients.

So administrators lump us all together as providers. No kidding they do, we're providers. The two ACP authors, one a lawyer and one a doctor, attempt to make a fairly erudite case that provider is bad for everyone involved. They favor calling people clinicians or healthcare professionals.

Now I mentioned this piece in the cardiology podcast because A it's made the rounds on social media with many hundreds of accounts tweeting about it, and eleven news organizations wrote stories about the ACP paper. And of course it stirs emotions in many of my colleagues to be called a provider. So my comments I too was initially hacked off by the term provider.

But over the years, I have come to realize that being mad when a mid-level manager calls you a provider is like being mad when it rains. It's pointless. No matter what the ACP authors write, what we are called uh does not matter to the patients who ask for our help, right? It doesn't matter to the person with heart block who needs me to put in a pacemaker in the afternoon.

It does not matter to the patient with a heart attack who needs my colleague to get out of bed and open his LAD at four o'clock in the morning. It does not matter to the dying patient and family who we sit with and help ease this process. Maybe it is my age, but I've come to believe that our calling to help people who are asking for our help is the same as it always was.

And I love it just as much, perhaps more now than I ever did. The other stuff, like being called a provider or having to do safety modules, is just noise. Perhaps though it's worth thinking about how the transition from doctor as a professional to doctor as an employer actually happened. I think there's two big causes. The first cause was when we, doctors, decided to become employees rather than independent practitioners.

When I joined a pra private practice group in 1996, we went to all the hospitals in the city. So it was about twenty of us. If one hospital cut cath lab staff or cut services, we shifted business to the other hospital. In other words, hospitals competed for our business. They worked for us. We were our own bosses. Now it came with the headaches because we had to hire people to do the business of medicine, but we had our independence.

Around 2010, the compensation changes in the US, and doctors decided to work four hospitals. And there was an initial pot of gold, right? A signing bonus that came with it. And then there was a honeymoon period of a year or two where we still had some control. But soon enough Doctors became the same as the worker who loads cones on the truck, because an employee is an employee. Now the second cause of the provider moniker came when we decided to embrace shift work.

In the d old days a doctor saw patients in the hospital in the morning, then went to clinic, then went back to the hospital, and shared in a call schedule. A doctor was definitely not an employee then. But as we increasingly went to working shifts, which is clearly better for our lifestyle, we lost the continuity of being commander of the ship for a specific patient. It's easier to be called a provider when you leave at 5 p.m. and someone else takes care of your patient.

Now I'm not saying I want to go back to the old way because it was hard to miss kids ballgames and other things, but the new world of doctoring has downsides, and one minor one I think is being called the provider.

All right, next topic is coffee and dementia risk in jam on the less. Nearly 10 years ago, in 2017, I wrote a too-long essay calling for the end of coffee and blueberry and quinoa research. I called it a distraction to doing other important work and research. Here's the thing, no one listened. Almost every month there is some observational non-randomized correlational study published on coffee or chocolate or quinoa or bike helmets or whatever.

Well, to my surprise, this week, JAMA, JAMA, perhaps the second or third most important medical journal in the world. published another one of these observational studies looking at coffee and tea consumption and the risk of future dementia. Also, to my surprise, the authors are Harvard scientists. But not to my surprise, that was that higher caffeinated coffee use was associated with lower dementia risk.

The altmetric score of this paper is over three thousand. More than three hundred seventy news outlets covered the paper. It was even on national TV news, thousands more tweeted about it. But the paper's utterly worthless. It was a waste of time. I think its only use is as a teaching tool for evidence-based medicine classes.

Why? For two reasons. Because coffee drinkers surely have different baseline characteristics than non-coffee drinkers, and only a finite number of these confounding factors can be controlled for and adjusted for. But the larger flaw is that it belies any common sense that one substance such as coffee could reduce dementia risk by eighteen percent. I mean if you believe that You might believe a left atrial appendage closure device would provide benefit.

Now the reason I mention the silliness is that it is a measure of the health of scientific enterprise. That Harvard researchers would do such a study, and that JAMA would publish it indicates to me that medical science is severely sick. Instead of chasing discovery, scientists and publishers are chasing attention. Click.

News stories, altmetric scores. I don't have a solution for this problem, perhaps you do, but that these types of studies get done brings me sadness, and it really speaks to the poor health of our scientific enterprise.

Oh, I want to end on good news. The final topic today is a really nice paper and a really nice study. This is speaking of taking care of the whole patient who has AFib. Around the time of ablation, a group of doctors in Eindhoven, Netherlands decided to study an integrated lifestyle intervention in an RCT. Now this is a single center study, it's small, but it is randomized, and this is the way to know things in medicine. That is with randomization. They call it the POPAF, POP AF trial.

and they randomized patients with AFib who were going to have an ablation to standard pre ablation counseling by an EP doctor or a nurse led integrated lifestyle clinic, including a home sleep apnea test, weight reduction, alcohol reduction, smoking cessation, and optimal blood pressure and cholesterol treatment before undergoing the PVI.

Only one hundred forty five patients were enrolled, one-to-one randomization to the two groups. The primary endpoint was interesting. It was a composite of hospitalization for repeat ablations and cardioversions. The PVI in this study was done with PFA and And it was markedly positive. The primary end point occurred in fifty two times in the control group and twenty five times in the lifestyle intervention group.

That risk ratio was 0.49, the conference intervals were tight, the p-value was significant. Both the rates of repeat ablations and the rates of cardioversions were lower in the lifestyle group. Now the other notable finding was, and this is similar to what the Adelaide group, who really have been leaders in this field, found, the lifestyle intervention worked on metabolic risk factors.

patients in the lifestyle intervention group achieved substantial success in lowering BMI, blood pressure, and L D L, they improved their physical activity and to me These markers may be a greater health benefits than reducing AF episodes. So my comments. I like the study. I like the effort. Now the Adelaide Group has led the way in this area. Leaders they've been.

But most of their work has been observational and while their data is compelling, you always worry that people who decide to do the lifestyle intervention are different in ways that could improve their AF than people who decide not to do the intervention. That's why randomization is important.

The other thing I like about this small trial is the endpoint. Now the endpoint is not quite as hard an endpoint as an MI or stroke or death, but being admitted for a repeat ablation or a cardioversion captures a really clear outcome. The limitations of the study are obvious. It's single center and it's small and it's unavoidably open label. Now you could say that there was performance bias, but of course performance bias is sort of what's being studied in this intervention trial.

The authors note in their discussion that there's several other studies looking at the role of lifestyle interventions for AF, and I'm particularly curious about the role of GLP one drugs as adjuncts to AF therapy. It may turn out that these drugs are equally effective to ablation in patients with AF and obesity.

So taken together with the observational work from Adelaide, this study encourages us to not just destroy left atrial myocytes, but attend to the metabolic health of our patients with AFib. So that's it for this week in cardiology. As always, I'm grateful that you listened. Thank you. And remember, if you like this podcast, please take the time to write us a review, give us a rating. These things help others find us. Until next week, this is John Mandrola from the Heart.org Metscape Cardiology.

org Medscape Cardiology Any views expressed are the presenter's