Jun 27 2025 This Week in Cardiology

0:00 You're listening to this week in cardiology from the heart.org Medscape Cardiology. This podcast is intended for health care professionals only. Any views expressed are the presenter's own and do not necessarily reflect the views of WebMD or Medscape. Hi everyone, this is John Mandola from the heart.org Medscape Cardiology and this is this week in cardiology for June 27th, 2025. This week, FDA approves triple drug polyill. My opinion has changed on the polyill. A deep dive into invasive PE therapies, heart disease trends, and diabetes care is on fire. First, an announcement. Next Friday is our Independence Day holiday. It's one

0:47 of my favorite holidays. This week in cardiology will therefore return on July 11th. Also, next weekend is the start of the tour to France. And even if you don't love professional cycling, this year could be one of the best ever races as three of the best cyclists in the world come to the race fit and healthy. And I can't wait to watch. The second announcement is a sad one. I learned this week that fellow medical conservative Dr. Andrew Flappen of Edinburgh died suddenly. Andrew invited me to speak twice at the Royal College meeting. I have enjoyed my time with him immensely. He was a force of nature and a doctor's doctor. To my colleagues in Edinburgh, I offer my condolences.

1:32 Okay, first topic is FDA news in hypertension. The FDA this week approved the three component poly pill for hypertension. Its brand name is going to be called Wida Pill Plick, which is a really silly name. I can't even hardly pronounce it. The poly pill includes an ARB telmicardin, the calcium channel blocker amloopene, and the diuretic indipamide. There will be a standard dose pill with the standard doses of the three drugs, but there's also going to be two poly pills with lower doses. Now, my feelings have changed about the poly pill. I used to be dead set against it. I thought it was dumb and it would be far better to just titrate doses of selected drugs. But now I am more open to the whole

2:19 simplicity thing. As I age, I grow more and more interested in minimally disruptive care. A concept began by my May Mayo Clinic Dr. Victor Monttoi. The idea is that life is for living, not being a patient. Getting prescriptions filled is a huge pain in the butt these days. I've learned this firsthand. So the idea of taking one pill that has a better chance of controlling blood pressure is absolutely minimally disruptive compared to titrating two or three pills which each require a separate prescription. The evidence for polyill efficacy is quite decent. Lancet published an RCT comparing the triple poly pill to three different two drug combinations and it fared well. The

3:04 triple drug poly pill lowered the systolic blood pressure statistically more than the other combinations. Now this was a small efficacy trial but there were no significant differences in hypotension though more patients in the triple therapy arm had out of range sodium or potassium values but quote very few clinically significant electrolyte abnormalities occurred in any of the groups. Also in 2024, Jack published an RCT of about 300 patients who had mild to moderate hypertension. And this trial randomized in a 2 to 2:1 ratio of the polyill quarter dose which was telmartin 10 amloopene 1.25 and an adipomide 625. A polyill half dose which

3:52 was telartin 20 amloopene 2.5 and indipamide 1.25 or placebo. And it found that blood pressure reductions that delta versus placebo was about 7 to 8 millimeters per mercury. At week four, clinic blood pressure control that was defined by less than 140 over 90 was 37% for placebo, 65% for quarter dose and 70% for half dose. Both doses had highly significant p values and the adverse effects were similar. And then finally in 2023, JAMAMA cardiology published a metaanalysis of seven trials with,900 patients looking at three and four component poly pills versus monotherapy or placebo. Again,

4:39 the poly pills were more effective blood pressure lowering drugs and there was little or very little uh differences in adverse effects. Now I want to say a word of caution. These trials enrolled 59year-old patients. They had runin periods and in trials patients are motivated, clinicians are motivated and there are research nurses. In other words, the trial environment is seriously protective. The practice of evidence-based medicine though requires us the practitioners to be mindful of the external validity of trials. So giving these drugs in a single pill is not for frail elderly patients with serious comorbidity. Patients on these drugs should be given followup. But again, I stress the sole point of

5:26 preventive therapies like treating hypertension in middle age people is so that they become old age. When patients successfully make it to old age, there's a reason for caution. Benefits of preventive therapies become less and side effects become more frequently when they're used in older patients. The thing about the poly pill is that it offers a single best chance of getting control of blood pressure. Simple is better. Not only because it is less work for the patient, but in my experience, if you get early success, it's more likely to lead to adherence and end confidence in the clinician. I don't know how much this poly pill will cost. The three components are not at all costly, but putting them together could be and that would be sad. I am upbeat

6:13 about poly pills. I changed my mind. All right, next topic is a deep dive into invasive PE therapy, pulmonary embolism therapy. We need to talk about a new kid on the block and that is this business of interventional PE care. In my hospital, our two EP labs are bookend, the three Kath labs, and I like to visit the Kath labs as both a curious person and a journalist. I often see my colleagues treating PE and the pictures are impressive when a doctor literally sucks a clot out of the pulmonary artery. My former partner for decades, two decades, Tom 2, he became the chief medical officer of Anari. I loved working with Tom. Our cub cubicles and clinic were right close by. And by the

7:00 way, in private practice, you only get a cubby. My diplomas are not on the wall. They're in boxes. So Tom pushed me on the evidence and I once debated him in front of the entire medical staff about PCI for stable coronary disease. I had all the data and was sure I was going to win the debate and Tom told scary stories and I was crushed. Anyways, I liken endovvascular clot aspiration in PE to clot aspiration MI and cerebral protection devices in TAVER. Seeing clot that was once in the body has huge persuasive properties but but scary pictures of clot are not evidence. So the European journal open has published an eyeopening review on the

7:45 endovvascular treatment of intermediate risk PE. While I know what you are thinking review articles are terrible to read and I would agree in most cases but this review however by Armen Shar is superb. They're sharp, short sentences. There's lots of subdivisions. I'm going to link to this review article, and there are two reasons to read it. One is if you're interested in PE care, which is increasingly common in cardiology practice. And the other reason to read it is that is a shining example of the failure of evidence-based practice to determine best therapies. So, advocates of EBM should read it for its many lessons. Okay, here's a brief review. Now, PE is obviously a leading cause of cardiovascular mortality and morbidity.

8:32 But the hard part of PE treatment is that PE is not one thing. It's kind of like AIB in that way. PE can be mild, even incidentally discovered on a CT done for other reasons, and it can be severe and devastating, causing shock and collapse. The extremes make for easy decisions. But most people with PE present with quote intermediate levels of risk. Endovvascular procedures have increasingly been used in the past decade. And it's interesting that the increased use parallels almost exactly the rise of per teams. What's per pe response teams? Now since so few patients present with extremely high risk or extremely low risk, most endovvascular therapies are deployed in intermediate risk patients. The problem

9:19 is that there is little evidence for use of these procedures in intermediate risk. In fact, no guideline gives interventional therapy a class one recommendation in this case because there is not class one level data. Okay, let's start with the beginning. A word on risk stratification and basic management. Everyone agrees that the first step in PE care is to risk stratify using clinical lab and imaging parameters. The ESD defines high-risisk PE by hemodynamic instability, which is associated with a 30-day mortality exceeding 15%. These patients require immediate adjunctive intervention directed at reprofusion, either medical and novascular surgical to prevent death. By contrast, low-risk PE

10:07 characterized by a normal blood pressure, low clinical severity, and no evidence of cardiac dysfunction, these patients carry a low mortality risk of less than 1% and can generally be safely managed with anagulation alone, even in the outpatient setting. Intermediate risk patients ac encompass 25 to 60% of all hospitalized PE cases. These patients have stable vital signs, but other concerning features such as cardiac dysfunction. Short-term mortality rates in intermediate risk PE range from 1 to 3% in clinical trials and 3 to 5% in observational studies. And according to the ESC, patients with both imaging and laboratory evidence of cardiac dysfunction should be deemed

10:53 intermediate to high risk. And this is where the controversy and uncertainty come in because of the limited data. Okay. What's the rationale for endovvascular therapy of PE? Where did it come from? Well, it stems from a seminal trial called PO. P EI ho. This was in 2014 in the New England Journal of Medicine. The RCT was of systemic litics plus Hepin versus Hepin alone in a thousand patients with intermediate risk PE and that study found a small benefit in its primary efficacy endpoint which was 7-day mortality and hemodynamic compens decompensations. It was like 2.6 versus 5.6. So that sounds good, right? A p value of 0.02.

11:41 However, this was outweighed by the risk of major extraranial intraraanial bleeding. Extraranial bleeding was 6.3% versus 1.2% and intraranial bleeding was huge 2.4 versus 2% and both those were highly significant. Thus the rationale for endovvascular therapies was born because systemic litics worked but were far too dangerous. All right. Now the next topic of the paper is how lacks FDA regulation led to this dubious evidence. So five endovvascular devices hold indications for PE therapy in the US. In 2014, the ECOS ultrasound assisted thrombolyis catheter from Boston scientific became

12:27 the first FDA authorized endovvascular therapy in acute PE. This catheter was initially studied in a small RCT and a prospective cohort study and both of these studies demonstrated short-term improvements in the RV to LV ratio. Thereafter, get this, four analogous quote, analogous devices have passer in the FDA 510K pathway where a device only has to be shown similar to a previous device. Now, these include cloud extraction devices of one sort of another. Now, the authors of the review paper in European Heart Journal Open then discuss four important and yet unanswered clinical questions. This is a nice way to do a review by the way. So one question is surrogate validity. Measures

13:14 of RV dysfunction such as RV size greater than LV size have been adopted in earlier studies because these were associated with early mortality. But experts now including the AHA guideline writers acknowledge uncertainty as to whether rapid improvements in RV dysfunction is a reliable surrogate for outcomes. I would add that RV size is like your LDL. No one cares about their echo image. They care about being alive and breathing well. All right, another remaining question. Question number two asks whether interventional therapy plus anti-coagulation beats simple anti-coagulation alone in the short and long term. Only three small trials have addressed this question and the results are mixed. Less than 200 patients have been studied in

14:01 RCTs with these devices. And I know it's crazy. And again, I remind you that the FDA allowed these device based on similarity to others, not evidence of benefit. Remaining question number three is whether endovvascular therapy added to anti-coagulation improves clinical outcomes for patients that include mortality, hemodynamics, symptom resolution and squelli that contribute to long-term mortality such as the chronic thrombboic pulmonary hypertension or poste impairment syndrome or recurrence of disease. For instance, in intermediate high-risisk PE, short-term mortality might range from 1 to 3%. But chronic pulmonary hypertension develops in 2 to 3% and post PE impairment in 10 to 30% of

14:46 patients. And despite the rise in endovvascular therapy, there still have been no RCTs. Now, the good news is that there are at least three ongoing trials. My hospital is participating in one of them. And I'll tell you that the problem is extremely strict entry criteria and that's going to limit external validity. But the fourth remaining question of course is safety of endovvascular therapy. While all the devices limit systemic thrombolyis which is a good thing, some of these catheterss involve large bore catheterss in the heart and the authors site a large real world non-industries supported observational study published in the journal of society of cardiovascular angography that found much higher rates of major bleeding when endovvascular therapy than

15:33 previously described. These were up to 10 to 15% and I'll cite that study. All right. The European Heart Journal Review article and authors devote another section to explaining the popularity of these devices in the absence of evidence. And I found this a really interesting read. Let me review some of it. One cause of the popularity of these interventional devices are the per teams who are led by interventional-minded doctors. Another and perhaps stronger tailwind for the excitement behind these devices is reimbursement changes. Now, I did not know this, but following an FDA 510K market approval, insurers independently determine if they will cover a device. Now, CMS is the largest insurer and its

16:18 decisions influence private insurers. But in 2021, CMS controversially ended its non- coverage policy for PE devices, which then allowed local Medicare contractors to decide. This decision by CMS accelerated coverage and in turn accelerated use of these devices. CMS, the authors wrote, could have required ongoing evidence generation within its CED mechanism, that is its coverage with evidence development, but alas, they did not. And by the way, a sidebar here is I feel like that the concept of coverage with evidence for everything new could be the most important policy ever employed. Now the third reason for rising popularity of these treatments is

17:04 marketing of observational research. Now we know this this is a common thing. Industry sponsors registries. The registries are voluntary. So only the best patients get in them and so the registries studies produce favorable results and then these favorable results get made into ads. Companies then spend money paying doctors to speak and travel. Here is a direct direct quote from the paper. Quote, "Until its recent acquisition by Striker, Anari Medical was a relatively young company that derived twothirds of its revenue from the flow sales. Since its initial public offering in 2020, the company had rapidly increased its volume and magnitude of general physician payments.

17:50 In 2020, it made 3,500 general payments to physicians, amounting to nearly a million dollars. Over the next three calendar years, 21, 22, and 23, these figures increased to 2.5, 4.9, and 6.7 million, respectively, representing 0.9, 1.2, and 1.4% of its topline revenues. Now, it's not just physicians who are making out here. Hospitals, too, benefited financially via higher DRG reimbursement rates. This is hilarious. Get this. Hospitals get paid on severity of disease. Using a device increases severity, so it's self-fulfilling. Here's another quote from the authors.

18:36 Quote, "Between 2021 and 22, the reimbursement for endovvascular therapy for PE with major coorbidity or complications nearly tripled from $9,000 to $25,000. Accordingly, an interventional PE service line can generate high revenues for a hospital system. End quote. Boom. There you go. PRT teams, per teams make money. Now, I don't mean to beat up the PE treatment people. I highlight this topic because of its EBM lessons. In the heyday of cardiology, we were leaders in the generation of evidence. We generated tons of evidence. Postmi care, heartfire care. in arhythmias we had cast and affirm so it's weird that the same

19:22 evidence generated in ethos did not infect the PE world now which of these devices if any is better is a knowable question but it won't come from observational studies it has to be via RCTs and I realize that PE patients come in different varieties but nonetheless these studies could have been done and then we would know and you might say John well there's ongoing trials now calm And my counter to that is it's largely too late. Equipoise has been injured. When you return from a clot extracting course on a beach resort, do you think you're going to be energized to randomize a PE patient in a trial or do the clot extraction? When reimbursement is favorable, do you think doctors will be keen to randomize or do the

20:08 procedure? I have already sent multiple notes to my friend Vani Prasad encouraging him and Marty Mccari at the FDA to do something to tighten device regulation. I'm not against approving early generation devices, but there has to be stronger postmarketing requirements for evidence with trials and there currently is not. But in truth, as professionals and scientists, we should not need the FDA to help us. We should want evidence. We should require evidence before exposing our patients to unproven therapy. Sadly though, the recent experiences with left atrial appendage occlusion and PE and now of course tricuspid valve interventions don't shine a favorable light on the scientific aspects of our

20:54 profession. All right, next topic. Heart disease trends. The Journal of the American Heart Association published a very interesting paper on trends in heart disease mortality. It really makes you think. A Stanford le team used the National Vital Statistics at the CDC to present data on heart disease mortality over the past 50 years from 1970 to 2022. Here was some key findings and and some of it was good news. Heart disease deaths are decreasing. In 1970, heart disease accounted for 41% of deaths. That has declined to 24% of all deaths. and life expectancy went from 71 years 1970 to 77.5 in 2022.

21:43 Now the proportions of types of heart disease deaths have changed dramatically over the p past 50 years. Age adjusted heart disease mortality decreased by 66% from 1970 to 2022. In 1970 more than 90% of heart disease deaths were eskeemic. Es schemic causes of CV deaths declined to 53% in 2022. Now one of the reasons may be this statistic. Since 1970, age adjusted mortality from AMI decreased by 89% from 354 in 100,000 to 40 in a 100,000. Since 1970, age adjusted mortality from

22:29 any eskeemic de disease decreased by 81%. But conversely, since 1970, age adjusted mortality from other heart disease subtypes has increased by 81% with the greatest increases in heart failure, 146% increase. hypertensive heart disease 106% increase and arrhythmia 450% increase. For instance, in 1970 those other subtypes heart failure, hos hypertensive and arrhythmia accounted for just 9% of heart disease deaths. Now these other subtypes account for nearly half, 47% of heart disease deaths. So what are my comments? First is that the authors

23:15 rightly acknowledge limitations in the use of coding. For instance, disease names have shifted somewhat and arrhythmia related deaths may in fact be related to underlying eskeemic heart disease. So es schemic heart disease could be underounted. But limitations aside, it's worth thinking about the data. The fallen death from AMI and eskeemic heart disease represents a shining example of excellence in both cardiology and I'd say public health. The reduction in smoking stands out as a huge success in public policy and surely this has enhanced the lives of millions of people. I would also la my interventional colleagues. I spend a great deal of time on this podcast criticizing the overuse of intervention in stable CAD. But the acute treatment

24:02 of MI has been one of the most important medical achievements of a generation in all of medicine, not just cardiology. Young people who listen to this podcast cannot appreciate where we were when I began medical school in 1985. MIS then were largely treated with morphine and swan gans catheters. Now people come in with an anterior MI and they leave with a band-aid on their wrist and a normal ejection fraction. So impressive has been the trends in AMI care, it's hard to even find an eskeemic cardiammyopathy patient who qualifies for primary prevention ICD. Keep in mind too that this marked reduction to MIT bears on screening for heart disease. Namely, the better we get at treating a condition, the less value there is in finding it early. We don't

24:48 screen for appendicitis or gallbladder disease or pneumonia because we can simply treat those problems when they occur. Now, acute MI isn't quite there, but it's approaching that. By the way, if you're young and looking for a job that has meaning, I can't think of a better job than interventional cardiology. Nearly every day you are saving or enhancing a life. The problem of course with interventional cardiology is that it is hard because like delivering babies, MIS happen at all hours. Another factor in the reduction of death from schemic heart disease could be statins. Right? Statin use has gone from about none 1970 to 45% of adults over the time frame. Since we know that statins consistently reduce CV events by about 25%, not having an MI in the first

25:36 place is a good way not to die of eskeemic heart disease. I for one think statins play a consequential role in lower eskeemic heart disease deaths, but smoking and MI care are much larger causal factors. Now my final comment is the alarming language both in the paper and online regarding the rise in other forms of heart disease. And yes, the rise in obesity which has led to more hypertension and more aphib and more heft is a big concern. I don't want to downplay it. Obesity is a public health crisis and largely a public health failure. But on the other hand, it's important for doctors to understand that all people die. If you reduce MIS and increase life expectancy, what do you think happens? People get older and they

26:22 die of other diseases such as heart failure, atrial fibrillation, dementia, cancer, and falls. This is normal. It's still a good thing to extend life and enhance life. But it's also important to recognize that reducing eskeemic heart disease deaths does not magically reduce health care cost because eventually aging people develop some sort of disease and if it is treated, money is spent. That's fine. The reason to improve treatment of heart disease is not to save money. It is to extend quality of life. If our therapies do that, then it is worth the money spent. All right, next topic and final topic. It's just short. It's diabetes. I'm not going to go into the specifics, but at the recent ADA meeting in Chicago, there

27:08 was a trove of studies and news that come out that should be on our radar. For instance, a study showed early data on once weekly insulin. Think about that if you have type 1 diabetes once weekly in insulin. There were early studies on other GLP drugs as well as combination of drugs. And I think my friends that semiglutide and tzepide may become the simatans of GLPS soon. There was even some encouraging data on recombinant gene therapy for type 1 diabetes. The diabetes world is advancing fast and I think it's only a matter of time before cardiologists are prescribing GLP-1 drugs like we did for SGLT2 drugs. And finally before I close I'll say that there's been another BMJ investigation

27:53 on more potential emphasis potential troubles in the tyagular evidence base and I'm going to look into this over the holiday and I'll have a report on ne on the next uh TWWIC podcast. I will see you again in week two of the tour. And 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, take the time, give us a rating or write us a review. This helps others find us. And of course, if you don't agree with something I said or have something to add, send me an email or write a comment on the website. I always learn from listener feedback. until two weeks. This is John Mandola from the heart.org Medscape Cardiology.

28:43 You're listening to this week in cardiology from the heart.org Medscape Cardiology. This podcast is intended for health care professionals only. Any views expressed are the presenter's own and do not necessarily reflect the views of WebMD or Medscape.