Dr John M

cardiac electrophysiologist, cyclist, learner

Survey for Athletes with AF

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Hey Athletes:

My colleague, Professor Rachel Lampert, from Yale, along with the StopAF.org patient group, seek to learn more about how atrial fibrillation (AF) and its treatments affect athletic people.

If you are an athlete or if you regularly exercise vigorously, please give the Yale researchers a few moments of your time.

Here is the link to the survey.

Since I had AF in the past, I filled it out. It takes only a few minutes.

Prof. Lampert’s research into this area is important because AF affects people in vastly different ways.

It’s weird; while most AF stems from advanced age or lifestyle diseases (obesity, high blood pressure, alcohol excess and sleep apnea), endurance sport represents a special circumstance.

The added problem for athletes with AF is that most doctors do not (really) understand our goals and expectations. This sort of research sheds light on the inner workings of the athletic persona.

The other reason to do the survey is that Prof. Lampert is really nice.

JMM

Still Negative on Watchman

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Many readers have contacted me to ask whether my negative viewson left atrial appendage occlusion with Watchman have changed since 2017.  

The short answer is no. My views are even more negative today. 

In 2016, I published an editorial on theHeart.org | Medscape Cardiology arguing that this procedure should stop. One of the rebuttals was that it was a blog post, not an academic editorial.

Months later, Andrew Foy, Gerald Naccarelli and I put the same argument into academic-speak and the influential journal Heart Rhythm published it.[1]

I have debated and presented this topic multiple times in the US and Europe. 

The newest data on Watchman have reinforced my negative view.

Efficacy Issues: 

Two studies published in 2018, one from Watchman investigators,[2]and the other from independent French researchers,[3] found high rates of device-related thrombus on follow-up echocardiograms (Translation: clot stuck to the device). This is not surprising since the Watchman is a foreign body left in the heart.

This data also helps explain why, in the Watchman vs warfarin trials, ischemic stroke (due to blockages) rates were HIGHER in the watchman arm. 

Both these papers reported that clots on the device go away with clot-blocking drugs called anticoagulants. That’s an existential problem because the main reason for having the device put in is to avoid the need for anticoagulation. 

Procedural Complications Higher After Approval: 

A group of researchers from the University of Kansas assessed the safety of Watchman after its FDA approval.[4] 

They used the FDA MAUDE database to assess the rate of complications divided by the number of implants.

This figure from their paper shows the higher rates of procedural complications after approval. Most sobering is that events in MAUDE surely under-estimate the true incidence of complications. 

Moral Hazards:  

You should also know about the moral hazards faced by US hospitals and physicians putting in this device.

Boston Scientific, the maker of Watchman, charges the hospital a large upfront fee to start a left atrial appendage occlusion program. Then they create price incentives that kick in if a hospital does “enough” Watchman procedures. To break even or make money with this device, one has to do a not-small number of procedures.

Given the asymmetry of information in the doctor-patient relationship, this moral hazard is downright ugly.

Unmet Need: 

During my debates and in discussions with colleagues at my hospital, I am asked what to do for patients with atrial fibrillation who are at high risk for stroke and cannot take anticoagulation.

Some doctors feel they have to offer this procedure as an option. This, I believe, is wrong-headed. 

If a patient had cancer and studies showed chemotherapy did not work for that type of cancer, the doctor should not offer the chemotherapy—in the name of “doing something.” 

In Medicine, doctors should not offer therapies that do not work. 

I have studied the evidence—not the spin–for left atrial appendage occlusion and this much is clear: it is an invasive procedure with a high risk of complications, and when it was compared to anticoagulation, it did not prevent ischemic strokes. 

Patients who could not take anticoagulants were excluded from the Watchman trials. While the absence of evidence is not the same as evidence of absence of an effect, the data we have on Watchman predicts higher risk patients will likely do worse with Watchman.

Summary: 

I do not recommend this procedure. Period. There are ongoing trials now in Europe. If these trials show benefit, I will reconsider this approach.

I am a medical conservative.[5]

This means I recommend expensive invasive procedures only when the benefit is greater than the harms. This is not the case for left atrial appendage occlusion with Watchman.

References:

1.         Mandrola J et al.Percutaneous Left Atrial Appendage Closure is Not Ready for Routine Clinical Use. Heart Rhythm. doi:10.1016/j.hrthm.2017.10.007.

2.         Dukkipati Srinivas R. et al.Device-Related Thrombus After Left Atrial Appendage Closure. Circulation2018; 138(9): 874–885. doi:10.1161/CIRCULATIONAHA.118.035090.

3.         Fauchier L et al.Device-Related Thrombosis After Percutaneous Left Atrial Appendage Occlusion for Atrial Fibrillation. J Am Coll Cardiol2018; 71(14): 1528–1536. doi:10.1016/j.jacc.2018.01.076.

4.         Jazayeri M-A et al.Safety profiles of percutaneous left atrial appendage closure devices: An analysis of the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database from 2009 to 2016. J Cardiovasc Electrophysiol2018; 29(1): 5–13. doi:10.1111/jce.13362.

5.         Mandrola J et al.The Case for Being a Medical Conservative. Am J Med2019; 0(0). doi:10.1016/j.amjmed.2019.02.005.

AF, Ablation, Stents and Five Nuances

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Joan has left an excellent comment on my recent 2019 AF ablation update.

She brings up many important issues. Let’s dissect it.

Q: Joan asks if it is common to see patients who think they are cured after AF ablation but are still in AF? 

A: The scenario I described in my previous post is not common, but it is not rare. Since AF ablation entails much instrumentation and many burns, it can affect how the heart feels things. The heart has its own nervous system; yes, the heart feels. Also, the bigger the procedure, the bigger the placebo effect. 

Q: If ablation doesn’t work, then I sure know a lot of people walking around who had ablation and are convinced it changed their lives. 

A: First, I did not say AF ablation does not work. I wrote that we don’t know; it has not been adequately tested in a placebo-controlled blinded trial. 

But let’s consider how ablation might change people’s lives without eliminating AF. 

The sites of ablation in the left atrium are close to neural inputs to the heart. It may be that we change how the heart perceives AF simply by instrumenting the heart and ablating in the areas near where the nerves attach to the heart. This statement should induce little surprise because the majority of people who have AF do not know it. All cardiologists have observed a huge disconnect between an actual heart rhythm disorder and its symptoms.

A Canadian study called DISCERN AF found that the ratio of asymptomatic to symptomatic AF episodes increased more than threefold after ablation.[1] In 2017, a study called CAPTAF found that AF ablation compared with drugs improved quality of life, but the improvement occurred without a statistically significant reduction in AF burden. Hmm?

Another problem with assessing “success” of AF ablation is uncertainty about the meaning of AF episodes. That sounds like a crazy sentence, as AF on an ECG defines the condition AF. The traditional way to determine ablation success is the absence of even 30 seconds of AF on any monitor. That makes little sense because if someone had persistent AF before the ablation and after the procedure has a couple of 30-second episodes a month, why isn’t that a success?

But it’s even more complicated than duration of AF episodes. We are beginning to understand that AF on an ECG may be an end-result of underlying atrial disease. In other words, the AF may be a symptom or sign of other stuff that is awry in the body and negatively affecting the atria. (Stress, high blood pressure, inflammation from fat around the heart, and many many other things.)

An apt analogy is infection and fever. When we get a bacterial infection, we also get fever. The treatment of a bacterial infection is to kill the bacteria with antibiotics not just relieve the fever with acetaminophen. Is AF ablation acting like acetaminophen—merely covering up something else?

This is a super disruptive notion because in the past we considered the electrical episodes of AF as a good surrogate marker for symptoms and a predictor of stroke. 

There are many studies showing a poor (temporal) relationship of AF episodes to stroke—meaning, when people with AF had stroke, they often had no AF episodes before the event. How could that be if AF caused stroke? What’s more, AF drugs reduce AF episodes but don’t reduce the rate of stroke? How could that be if AF caused stroke? Dr. Hooman Kamel has written one of the most important papers on AF. [2] He and his co-authors make the case that we need a new framework of understanding AF and stroke. I would say.

Q: You have done AF ablations for a long time, are your personal observations irrational or unscientific? 

As for my experience with doing more than a thousand AF ablations over 15 years, I believe the procedure helps people. I wouldn’t do it otherwise.

But I am not sure; and the procedure is expensive, invasive, risky and… it needs to be tested.

If medicine is to be scientific, we must ascribe to the Feynman principle: “the first principle is that you must not fool yourself and you are the easiest person to fool.”

Doctors have been fooled often. 

  • Cardiologists used to use pacemakers to treat benign fainting. Until this was reversed in a placebo-controlled trial.
  • Heart surgeons used to tie off the internal mammary artery to treat chest pain. Until it was reversed in a placebo-controlled trial. 
  • When I came to Louisville in the 1990s, heart surgeons were doing transmyocardial laser revascularization–burning holes in the heart for the relief of angina. This was reversed in a placebo-controlled trial. 
  • Neurosurgeons used to place embryonic fetal cells into the brain for Parkinson’s disease. This, too, was reversed in sham-controlled trial, which even involved drilling holes into the head of patients in the placebo arm. 
  • Orthopedists used to think knee arthroscopy for arthritis reduced pain. Nope. This common practice was reversed in placebo-controlled trial. Here is review article[3]describing five ortho surgeries, including the common procedure called vertebroplasty, which have been proven not to work by sham-controlled trials. 

Q: How can patients agree to be in a placebo-controlled procedure trial, and would insurance pay for it? 

The way ORBITA investigators arranged for a placebo arm of their trial was that all the patients were promised the stent procedure; the ones in the placebo arm simply had to wait a few weeks–after the treadmill test and questionnaires were done. For AF ablation, this period will be longer, probably six months to a year.

On the matter of insurance, in an American system of private insurance, providers can change each year. That means there is little incentive to keep people healthy in the long term. Thus, there is little incentive to pay for people to be in a placebo-controlled trial. But in most countries, the government pays for healthcare, and would have an extreme incentive to prove whether or not a costly procedure works.

Q: Stents are still being used. How could this be given the “weird” ORBITA study? 

The tricky thing about stents are that they work great for patients having a heart attack, but no study shows they work (on average) for patients with stable heart blockages. 

While the use of stents for stable blockages has decreased, the practice still continues in earnest. The way around this is use of different diagnoses. Instead of saying the stent is being used for stable coronary disease, doctors often label the symptoms as unstable angina. [4]

The core reason stents are being used despite numerous studies showing that they do not reduce heart attacks or death is that the clogged pipe theory of heart disease is deeply engrained–among doctors and patients alike. It will take decades to change this thinking. (Though there is one more trial testing stents; it’s called the ISCHEMIA trial and it’s had its share of controversy.[5])

Nobel winner Max Planck famously said that science advances one funeral at a time. This is often true in Medicine. 

Resistance to de-adopt unproven therapies is one of the reasons I am a medical conservative, and why I advocate for evidence of benefit before therapies are accepted.

References:

1.         Verma A et al.Discerning the Incidence of Symptomatic and Asymptomatic Episodes of Atrial Fibrillation Before and After Catheter Ablation (DISCERN AF): A Prospective, Multicenter Study. JAMA Intern Med2013; 173(2): 149–156. doi:10.1001/jamainternmed.2013.1561.

2.         Kamel H et al.Atrial Fibrillation and Mechanisms of Stroke Time for a New Model. Stroke2016; 47(3): 895–900. doi:10.1161/STROKEAHA.115.012004.

3.         Louw A et al.Sham Surgery in Orthopedics: A Systematic Review of the Literature. Pain Med2017; 18(4): 736–750. doi:10.1093/pm/pnw164.

4.         Wadhera RK et al.Association of the Hospital Readmissions Reduction Program With Mortality Among Medicare Beneficiaries Hospitalized for Heart Failure, Acute Myocardial Infarction, and Pneumonia. JAMA2018; 320(24): 2542–2552. doi:10.1001/jama.2018.19232.

5.         Rajkumar CA et al.‘Faith Healing’ and ‘Subtraction Anxiety’ in Unblinded Trials of Procedures. Lessons from DEFER and FAME-2 for End Points in the ISCHEMIA Trial2018; 11(3). doi:10.1161/circoutcomes.118.004665.

AF Ablation Update 2019

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Most years I write an update on any big developments in AF ablation.

This year’s version will be a short one. I have little new to report. But it’s worth reviewing some basic issues.

We still do not know the cause of atrial fibrillation (AF). That makes it hard to fix with ablation.

Knowledge Deficits:

To explain why not knowing the cause of AF impairs our ability to ablate it, it’s useful to compare AF ablation to WPW ablation. Wolfe-Parkinson-White or WPW syndrome causes rapid heart rates because of an extra pathway from the top to the bottom (atria and ventricle) of the heart. You can cure WPW by ablating the extra pathway–often with one burn.

The approach to AF is to use single burns (or cryo-balloon lesions) to electrically isolate the muscle bundles surrounding the pulmonary veins. Think of that one burn (used in WPW ablation) times 60-80 to form electrical fences around the pulmonary vein orifices. This is called pulmonary vein isolation or PVI. Studies show that it is the best technique for ablating AF.[1] It’s what we did in 2004 and it’s what we do now.

The problem is that sometimes AF is triggered by cells in the pulmonary veins, and sometimes it is not. That means we could be doing 60-80 burns in the heart and not going after the right target. There is NO way to tell. The good news, though, is that the pulmonary veins are involved often.

The other problem is that even when AF is being triggered by cells within the pulmonary veins (e.g. we are going after the right target), the lines of block from the burns are not durable, and over time, electrical activity can leak out through a gap in the line–thus causing AF.  The weirder thing is that sometimes these gaps occur in patients who don’t have AF after the ablation. IOW, the burns did not completely isolate the veins and AF still stayed away.[2] That observation suggests the burns hit something–but we don’t know what.

AF Ablation Remains Untested: 

The larger problem with AF ablation is that it has never been adequately tested. In medicine, to know if a pill or surgery really works, you have to test it against a placebo in a blinded trial. Emphasis on blinded. A new medicine cannot get approved unless it works better than a placebo. Procedures should require the same proof.[3]

AF ablation has never been tested against a placebo procedure–sometimes called a sham procedure. Every single study of AF ablation has been confounded by the patient and doctor knowing the treatment. Or, as we say, AF ablation trials are unblinded.

I know; exposing people to the risk of ablation without actually doing the ablation sounds nutty. But the list of procedures and surgeries proven useless when compared to placebo is long.

The most recent shock was stents in the heart for the relief of chest pain due to chronic and stable blockages in the coronary arteries. Millions of people worldwide have received stents, and both doctors and patients believed the metal cage relieved chest pain called angina. How could it not? The stent essentially fixes a 90% blockage to 0%.

Except … stents did not pass the placebo test!

In the ORBITA trial[4], a brave group of researchers from London randomized 200 patients with a single severe blockage and chest pain to either a real stent procedure or a fake procedure. The patients and the doctors taking care of them afterwards did not know which they had. To measure the effect of the stent vs the sham procedure, the researchers walked all 200 patients on a treadmill before and after the procedure, and, shockingly, there were no significant differences in exercise time, nor were there any significant differences in chest pain on questionnaires. In case you find this hard to believe, the ORBITA investigators counter the many criticisms of their trial in two worthy rebuttals.[5,6]

The message is clear– if fixing a 90% blockage does not relieve chest pain any better than a sham procedure, then it’s possible that the quality of life improvements reported after AF ablation might also be a big placebo.

A quick story: I did an ablation on a patient who had terrible AF. Terrible in that AF was causing depression, shortness of breath, dizziness and the man told me that he didn’t care if he died during the procedure, he could not live like this. I did the ablation and it went well. A year later, he told me in the office that I was a miracle worker. I had given him his life back.

Except … sit down for this... he was in AF!

I am giving a talk at the Heart Rhythm Society meeting this year on why we need a placebo-controlled trial for AF ablation. I will, of course, address the ethics of exposing a a hundred or so people to the risk of a sham procedure vs the ethics of exposing millions to a potentially worthless procedure. (For the record: I predict an AF ablation placebo control trial will show a large placebo effect, but also a real effect.)

Two new trials in AF ablation in 2018: 

The CASTLE AF trial[7] showed that for patients with heart failure and AF who have failed medicines, AF ablation reduced the rate of death and heart failure by about 12%. The trial results sound great, but it only included relatively young, mostly male patients who had moderate heart failure. Most patients with heart failure and AF are older and have multiple problems that make AF ablation unlikely to work.

Important point here: you should only apply trial results to patients like those in the clinical trials. We call this the external validity of a trial.[8] I have written about this: Treating the Individual, Not the ‘Average’ Patient.

The CABANA trial, which is not yet published, showed that for patients with AF and risk factors for stroke, AF ablation compared with medical therapy did not significantly reduce the rate of stroke, death, bleeding or cardiac arrest. CABANA did show that AF ablation reduced AF episodes, and it improved quality of life, but, of course, CABANA was unblinded and had no placebo control. That is crucial because it was done by doctors who believe in AF ablation.

Summary: 

AF ablation in 2019 is about the same as in 2018.

I recommend it as an option for people who have well documented AF that…

  1. cannot be reversed with lifestyle measures such as weight loss, treatment of sleep disordered breathing, control of blood pressure, attainment of cardiorespiratory fitness, and reduction of alcohol intake, and
  2. cannot be suppressed with medicine, and
  3. impairs one’s quality of life enough to warrant having an invasive procedure with a risk of serious complications in the range of 1-3%. This latter point is important because once you educate people about AF, they become less frightened, and, when less frightened, the AF often becomes less burdensome.

The AHA and ACC recently published an update to the 2014 AF treatment guidelines. I wrote a few words on the new recommendations.

Here is the column: Ten Thoughts on the 2019 AF Treatment Guidelines.

References:

  1. Verma A et al.Approaches to Catheter Ablation for Persistent Atrial Fibrillation. New England Journal of Medicine2015; 372(19): 1812–1822. doi:10.1056/NEJMoa1408288.
  2. Sauer WH, Callans DJ. The Tribulations of Atrial Fibrillation Ablation Trialists. Circulation: Arrhythmia and Electrophysiology2016; 9(1). doi:10.1161/CIRCEP.115.003738.
  3. Redberg RF. Sham Controls in Medical Device Trials. New England Journal of Medicine2014; 371(10): 892–893. doi:10.1056/NEJMp1406388.
  4. Al-Lamee R et al.Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial. The Lancet. doi:10.1016/S0140-6736(17)32714-9.
  5. Francis DP, Al-Lamee R. Percutaneous coronary intervention for stable angina in ORBITA – Authors’ reply. The Lancet2018; 392(10141): 28–30. doi:10.1016/S0140-6736(18)31190-5.
  6. Al-Lamee R, Francis DP. Swimming against the tide: insights from the ORBITA trial. EuroIntervention2017; 13(12): e1373–e1375. doi:10.4244/EIJV13I12A217.
  7. Marrouche NF et al.Catheter Ablation for Atrial Fibrillation with Heart Failure. New England Journal of Medicine2018; 378(5): 417–427. doi:10.1056/NEJMoa1707855.
  8. Rothwell PM. External validity of randomised controlled trials: “To whom do the results of this trial apply?” The Lancet2005; 365(9453): 82–93. doi:10.1016/S0140-6736(04)17670-8.

Musings on the CABANA trial — AF ablation vs Drugs

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Last week at the Heart Rhythm Society meeting in Boston, Dr. Douglas Packer from the Mayo Clinic presented results of The Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial.

I cannot remember a more consequential HRS (Heart Rhythm Society) meeting. Before and after the presentation, CABANA talk dominated conversations amongst colleagues.

I wrote a column directed at an audience of doctors for the theHeart.org | Medscape Cardiology. You can find it here>  CABANA: Initial Thoughts on AF Ablation vs Drugs

CABANA is important. AF ablation is big business. Hospitals, doctors and the companies that make equipment for the procedure make lots of money from AF ablation. What’s weird about all this growth is that we have not had solid evidence that the procedure improves outcomes, such as stroke or death.

That’s the question CABANA addressed.

You take patients with AF who feel poorly and you put half the group on anti-arrhythmic drugs and the other half get ablation. Then you follow them for years and measure how many in each group have strokes, bleeding, death or cardiac arrest. Those four outcomes were called the primary endpoint. CABANA had many other secondary endpoints–how much AF occurred, quality of life, hospital admissions, etc.

CABANA works like a typical clinical trial: ask a question, then randomly assign patients to different treatments and decide what outcome to measure. The random assignment to treatment group is key because in ideal conditions the only difference between the group is the treatment–drugs or ablation.

The authors hypothesis held that ablation would be superior to drugs for reducing the primary outcome. Remember the primary outcome was disabling stroke, death, bleeding or cardiac arrest. Since the groups are randomized, and all other things equal, then if the ablation arm had fewer events, we could say ablation is superior. Or ablation caused the fewer events.

That is NOT what happened.

The number of primary endpoint events in the ablation and medication were very close–not even close to a statistical difference. The first line of the authors conclusion was that “ablation did not produce a significant reduction in the primary endpoint and all-cause mortality.”

Controversy:

After Dr. Packer presented the main results he then showed results depending on treatment received. In procedure trials some patients cross arms. (If drugs did not work, patients could have ablation, for instance.) So being randomized to an arm does not mean you have to stay in that arm. About 27% who were in the drug arm crossed over to the ablation arm while 9% in the ablation never received the ablation (mostly because of a change in mind.)

The authors knew this would happen and planned for it statistically. But crossovers do complicate the analysis.

Dr Packer showed the as-treated event rates and here the results favored ablation–with lower rates of the primary endpoint. This led some leaders in the field to say ablation was indeed superior.

But you can’t say this.

Statisticians call the use of as-treated comparisons scientific malfeasance. This sounds harsh, but the reason they say it is because when you analyze by treatment received you don’t preserve randomization. And, when groups aren’t randomized, you don’t know whether it was the ablation that caused the improvement or some other confounding factor.

The as-treated analysis essentially becomes an observational study — which make only associations, but not causation claims. (For instance, there are numerous observational studies showing that patients have fewer strokes after ablation, but no one uses these as proof because in observational studies, the reason is likely that healthier people have catheter ablation.) In CABANA, the patients that crossed over were likely different from those that stayed in the drug arm.

A Cautious Interpretation of CABANA: 

One way to interpret CABANA and preserve scientific rules is to say the trial did not actually compare ablation vs drugs as was intended but rather it compared the strategy of ablation vs initial medical therapy with ablation for recurring symptoms.In this scenario, there can be no claim that ablation is superior to drugs for reducing major outcomes, but we can preserve the possibility that ablation remains a reasonable option for selected patients with AF.

Safety:

Packer presented the safety outcomes of ablation vs drugs. He did not make any formal comparisons, but I tallied the total number of each and there were far more complications in the ablation arm. Surprisingly, there were no deaths related to the procedure, no atrial-esophageal fistulas and no major strokes. This is surprising because about a 1000 people had AF ablation.

Two things to remember about safety is that CABANA was done in experienced centers. I doubt that real-world everyday AF ablation is as safe as it was in CABANA. Second, the complications of AF ablation can have immense downside; they are asymmetric. When a middle-aged person has a stroke, or death from the procedure, this is especially tragic because he or she would surely not have died anytime soon of the AF.

The last thing to say about these results is that they are not yet published in a journal. That means it has not made it through peer review. We will learn more from the published paper.

Where to go from here: 

First, since CABANA found no significance difference in outcomes, we are left with the idea that ablation is done to improve symptoms or quality of life. This is a good goal for any treatment, but it’s hard to sort out how much ablation helps when patients and doctors know who received it. It’s why drug trials have a placebo control.

At least three investigators I spoke with are now planning a placebo-controlled sham trial. In this sort of trial, patients and caregivers are blinded to whether or not an AF ablation is done. Half the group will get a basic EP study, and ablation of arrhythmias on the right side, and no ablation in the left atrium–where AF comes from. The other half gets regular AF ablation. Then no one knows, and the patient is followed.

The history of such placebo controlled procedures have shown that many interventions we thought worked did not do any better than a placebo procedure–renal denervation, vertebroplasty, and placing stents in coronaries for relief of angina.

I know, this may upset some of you. Indeed, a quick-thinking response to doing a sham-control trial is that is unethical to expose patients to a fake procedure. But when you think harder and slower, you realize that the far greater ethical dilemma is exposing millions of people to a risky procedure that produces mostly a placebo effect.

Second, CABANA does not change my current clinical practice. I see no reason to offer more or less AF ablation. I will still do the same general things:

  1. Assess the patients to find out why AF is occurring. Then treat that problem. If it’s obesity or sleep apnea, AF gets better with weight loss and better sleep. If the AF occurred because of transient stress, wait for the stress to past. If the AF occurs because of alcohol, counsel the person to drink less. If AF occurs because of excess training, reduce training.
  2. Remove fear and educate patients. This is the biggest thing. Many patients want stuff done because they fear AF. We teach them about AF and we warn that often times the most dangerous thing about AF can be our treatments. This sometimes takes multiple visits.
  3. If the patient has risk factors for stroke (age, high blood pressure, diabetes, prior stroke, heart failure, blockages elsewhere), we counsel on the benefit/risks of anticoagulation.
  4. If the AF is causing an excessive pulse, we give drugs to slow the rate, so as to prevent heart failure.
  5. If AF persists and if it causes symptoms, then we try drugs. I often use drugs in as needed way. For people with AF once or month or so, they can take an AF drug at that time.
  6. I reserve AF ablation for patients who continue to have AF despite treatment of risk factors and use of AF drugs. I remain a cautious AF ablation doctor.

CABANA has not changed this approach.

Why is Science Emotional?

The final thing to say about CABANA is that its failure to show benefit in outcomes caused some to be disappointed, sad even. Some acted as if it was a failure.

This is a weird view of science. CABANA and trials like it deserve our respect whether or not they show benefit of an anointed procedure or drug. Scientific experiments should be designed to find truth. If the truth is that AF ablation is not better than drugs, then that is really good to know.

Our goal as doctors is not to instrument as many people as possible, but to help as many people as possible.

Yes, there are some purists who say the trial was not powered to find benefit–meaning, the null results of CABANA could be wrong and there was actually a benefit, but the trial did not detect it because it did not have enough patients or had too many people not getting the treatment they were assigned.

This is a reasonable argument, though one must remember that if a treatment is really superior, it should not take thousands of patients to show that it works. Saying a trial found no difference  because it is underpowered often means that the two treatment arms are minimally different.

JMM

PS: I will not accept comments that contain personal anecdotes of AF. These are problematic because one of the first rules I tell patients is not to compare their AF or their AF treatment to others. AF affects people in many different ways.

Thoughts on CABANA — The biggest study in AF ablation in years

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(The CABANA trial is slated for release in two days at the 2018 HRS Meeting. Here is a preview.)

Technology has made modern life easier. This is good for lots of things, but not for avoiding atrial fibrillation (AF).

As people in Western society grow older, heavier, less physically active, more distracted, and perhaps more anxious, the growing epidemic of AF should surprise no one.

AF is a serious condition that can impair quality of life and cause complications such as stroke and heart failure. AF drugs are woeful, risk factors are hard to modify; these realities have led many experts to embrace catheter ablation of AF. Favorable reimbursement for AF ablation has also not hurt its growth.

Increasing enthusiasm for AF ablation, however, has occurred without robust outcomes evidence.

  • Does creating scar in the left atrium make people live longer or have fewer strokes?
  • Is the risk of the procedure balanced by better outcomes in the future?
  • Are AF episodes (recorded on monitors or smartphones) a good surrogate marker of trouble? We already know that AF ablation reduces AF episodes compared to drugs, but to what end–does this reduction in episodes translate to less stroke, longer life or or fewer  heart failure admissions?

This is why The Catheter Ablation vs Antiarrthymic Drug Therapy for Atrial Fibrillation (CABANA) trial[1] may be the most important trial in modern electrophysiology. Dr. Douglas Packer from the Mayo Clinic is set to present CABANA findings this week at the 2018 Heart Rhythm Society Scientific Sessions.

Here is a primer on what to expect:

We must first consider the type of patient included and excluded in the study. CABANA is an outcomes trial so the authors wanted patients with AF who had an increased risk of complications. They included patients similar to those in the famous rate- vs rhythm-control outcomes study called the AFFIRM trial[2]—those over the age of 65, or, if under 65, with at least one risk factor for stroke. Patients had to have documented AF and be eligible for both ablation and use of at least two drugs.

The authors excluded young patients with AF who had no risk factors, those who had already failed two or more drugs and those who had reversible causes of AF, such as post-op AF or alcohol-induced AF. Patients with hypertrophic cardiomyopathy and those with previous ablation were also excluded.

CABANA compared left atrial ablation (mandating pulmonary vein isolation) to medical therapy. Ablation could be done with various RF catheters or a cryoballoon.  Medical therapy could include either rate or rhythm-control drugs—which is important.

The distribution of rate vs rhythm medication used in the comparator arm deserves attention. It’s good that both rate- and rhythm-control strategies were allowed, because if only rhythm control drugs were allowed and then ablation did better, one could argue that ablation beat an inferior comparator. Letting doctors choose either rate-or rhythm-control mirrors regular practice and thus improves the external validity (generalizability) of the study.

Since CABANA is an outcomes trial, we also have to note any baseline differences in patients. Randomization usually sorts this out, but if more patients in one group received non-vitamin-K-oral antagonists, for example, that would be important.

CABANA recruited patients from more than 100 centers worldwide. That’s a lot of data and patients to keep track of. We must keep an eye out for dropout. One always looks at the rate of dropout vs the difference in outcomes. It hurts reliability if the trial has a 3% dropout rate and the absolute difference in outcomes was only 1%.

Clinical trials must choose an endpoint to measure. In CABANA, the original primary endpoint was mortality. That’s a good endpoint because it’s easy to count and not susceptible to bias.

The problem with death as an endpoint is that AF isn’t life-threatening in the short-term, and to show a difference in death rates requires a lot of patients. About halfway through the trial, CABANA leaders along with the data safety monitors met to address two problems–a lower than expected event rate, and slower than projected accrual of study subjects.

They did not have access to any treatment-specific outcomes but decided to change the endpoint to a composite of four outcomes–total mortality, disabling stroke, serious bleeding, or cardiac arrest.  Overall mortality was changed to one of many secondary endpoints.

Changing the primary endpoint allows for more events to accrue and makes finding differences between the treatment arms easier. But it also complicates understanding the trial because one has to see which of the primary endpoints “drove” the result.

One must also consider that two of four primary endpoints (disabling stroke and serious bleeding) are susceptible to ascertainment bias.

To learn more about adjudication of endpoints, I reached out to trialist Dr Milton Packer who explained in an email that in an unblinded trial, like CABANA, sorting out a disabling stroke from a non-disabling stroke could be tricky. All CABANA centers were ablation centers, so Packer asked, “Were investigators more likely to identify and report strokes that occurred in non-ablated patients? Remember, he added, the adjudication process only operates on reported strokes.”

Packer identified another tricky part of the CABANA results—the choice to analyze data using a time-to-first event approach. Here, a major bleed that occurs before a disabling stroke will mask the stroke. That means all strokes that occur in the trial may not be counted in the primary endpoint.

CABANA also includes 13 different secondary endpoints ranging from hard endpoints like death to softer endpoints like quality of life. One endpoint that you can expect to be better with ablation is freedom from recurrent AF episodes. But what if ablation dramatically reduces AF but there are no or minimal differences in outcomes? You see the problem: AF episodes might be a lousy surrogate measure. That would have great implications for digital AF screening.

Finally, the lack of a placebo controlled ablation arm will limit interpretation of subjective endpoints. I am sorry, but it’s true. Consider two key secondary endpoints, the decision to admit to the hospital for cardiovascular reasons and quality of life scores. Knowledge of the treatment arm surely affects these outcomes.

If CABANA finds no difference in mortality or stroke, and the only reason to ablate AF is to relieve symptoms, then a placebo-controlled AF ablation trial will be required.

Here are two posts I’ve written on AF ablation and placebo: Is AF ablation a big placebo?  and on theHeart.org | Medscape Cardiology: Could Ablation for AF Be an Elaborate Placebo?

References:

1.         Packer DL, Mark DB, Robb RA, et al. Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) Trial: Study Rationale and Design. American Heart Journal. 2018.
2.         A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation. New England Journal of Medicine. 2002;347:1825-1833.

Take-home messages from Western AF 2018

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The Western AF symposium may have had corporate sponsors, but it was no boondoggle. The sessions start at 0715 and go through 1830. Your head spins at the end of the conference. I learned a lot.

Here are some fast-writing thoughts:

New Energy Source for Ablation

Electroporation looks to be a promising new energy source for ablation. The problem with RF-energy, or cryo-energy, is collateral damage. The atria lie close to the esophagus, coronaries and phrenic nerves.

Electroporation “ablates” heart tissue without damaging structures nearby. It’s also called pulsed field ablation. This is damn early data. We have to wait for more studies.

Sham Trial for AF ablation is coming:

I wrote about this on theheart.org | Medscape Cardiology in 2016.

As long as the target for AF ablation is reduction of symptoms, then it has to pass a sham control.

Professor Carina Blomstrom-Lundqvist presented results of the CAPTAF trial, which was a study of AF ablation in relatively young people. She found that the difference in quality of life score after ablation was not driven by the difference in AF burden at 12 months. Translation: some people feel better after AF ablation but still have AF. That is provocative.

Two leaders in the field made comments on this:

In addition to comments from two of the giants in EP, I also spoke with another (unnamed) leader in EP who said his group has talked among themselves about doing a sham trial but did not want to broadcast it for fear that someone else beats them to it.

We need the sham trial to sort out the placebo effect of ablation. Look up the ORBITA trial.

Left Atrial Appendage Closure Meets little Resistance:

There were multiple talks on left atrial appendage closure. All of them positive. Again, Professor Gerhard Hindricks took to the Q & A microphone and expressed concern of the evidence in support of this procedure.

During one session in which a panel of EP doctors expressed great enthusiasm about the procedure, Dr. Elaine Hylek, an internal medicine doctor and trialist for anticoagulant drugs, stood up to the mic and said, “you guys are scaring me.”

Her concerns are similar to mine:

  • The evidence suggesting LAAO is noninferior to warfarin are not convincing
  • The device has not been tested in patients ineligible for anticoagulants (these higher risk patients may be less likely to benefit.)
  • The device has not been tested against the direct-acting oral anticoagulants, dabigatran, rivaroxaban and apixaban.

AF and Heart Failure:

Western AF celebrated recent publication of CASTLE-AF.

CASTLE-AF compared ablation of AF vs continued medical management in patients with heart failure. AF ablation reduced death rates and hospital admission for heart failure.

My comments on this trial induced great criticism from Dr. Milton Packer, a heart failure expert. Dr. Packer’s concerns centered on the methods of the trial.

Professor Jon Kalman (Melbourne, Australia) gave a talk that may have changed my mind about AF and heart failure. He discussed a recent study from his group called CAMERA-MRI. They studied patients with AF and heart failure, comparing a rate control strategy vs ablation. Patients in the ablation group had much greater improvements in heart function (as measured by the ejection fraction).

What this data might change is the idea that AF causes heart failure (heart muscle weakness) only if the rate is excessive. In CAMERA-MRI, all patients had good rate control. Those with heart rate control improved their EF by 4.4%. But those in the ablation group improved by 18%.

It’s possible therefore that the AF itself, the irregularity, or something else, contributes to weakness of the heart. CAMERA-MRI isn’t the only study that found this. The Bordeaux group published similar findings in 2004.

Heart rate control remains a crucial part of treatment for AF.  If you don’t get good heart rate control, heart failure is likely.

But the combination of previous studies on AF ablation and heart failure, and CAMERA-MRI and CASTLE-AF all point towards a benefit for ablation in suitable patients.

The latter point is key: CASTLE-AF enrolled young, mostly male patients with only moderate degrees of heart muscle weakness. This data does not apply to the vast majority of patients with heart failure who are older and have multiple other problems. EPs mustn’t run amok offering ablation to patients unlike those in the CASTLE-AF.

And we still need to answer Dr. Packer’s criticisms of CASTLE-AF.

Finally, Dr. Doug Packer from Mayo gave a prelude to the CABANA trial. This comparison of drugs vs ablation in older patients with AF will look at hard outcomes, like death and stroke. It will be a landmark trial for our field.

JMM

CASTLE-AF (Ablation) Trial Delivers Benefits — Was I Critical Enough?

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Doctors like me have performed AF ablation for more than a decade without knowing whether the major procedure improves outcomes.

That sounds crazy but it’s true.

Until now, the only evidence we had that doing all these burns or freezes in the heart helped people was that it made people feel better than they did taking AF drugs.

Better quality of life is important but it seems like a procedure this invasive and expensive should do more than make people feel better.

Well, now, we have evidence that AF ablation improves hard outcomes.

The trial is called CASTLE-AF. It took place in 33 centers across the globe. NEJM published it. Led by my friend Dr. Nassir Marrouche from University of Utah, the authors studied AF ablation vs medical management in patients with chronic heart failure.

Patients had to have an ICD, moderate heart muscle weakness and symptomatic AF. It took about 8 years to select 360 people to enroll in the trial.

The results were positive. Patients in the ablation group had much less AF (which can be measured with their ICDs), fewer admissions for heart failure and lower death rates.

The reductions in outcomes were massive, too. Death was reduced by about 50%.

I wrote a column on the CASTLE-AF trial for the heart.org |  Medscape Cardiology. It’s called Nine Things to Remember About CASTLE-AF. 

It was a hard post to get right. I am close to AF ablation. I ablate AF, and though I believe the procedure is massively overused, I still think it has a role in selected patients. I’ve seen AF ablation help people a lot.

The other thing that made this column hard to get right is that the outcomes were so impressive. A 50% reduction in death outstrips any known therapy for heart failure. How could a procedure that was only partially successful in getting rid of AF be that much better than things like beta-blockers, ACE-inhibitors, and ICDs?

In the post I mentioned some of the limitations of the trial–like the fact that investigators knew which treatment arm patients were in. This lack of blinding can bias the results.

My post generated intense criticism from Dr. Milton Packer, who is a very prominent expert in heart failure. His tone in the comment section was patronizing and sanctimonious towards me. He insinuated that my summary was too favorable and that may have been due to the fact that electrophysiologists stand to gain financially from doing more AF ablation.

The personal attack and patronizing tone does not bother me. Not at all.

Seriously, what bothers me was that Dr. Packer brought up many legitimate criticisms. And I am mad at myself for not raising them more clearly in my post.

For instance, CASTLE-AF had large number of patients lost to follow-up. Most troubling was that more were lost to follow-up in the ablation arm than in the medical arm. This is a big deal because the proportion of lost patients to the total number of events was high. Damn it, that should have been included in my summary.

Another criticism Packer noted was that the primary analysis was based on a small number of events. That raises the possibility that the results may not be replicated in future studies.

Packer also complained that randomized patients as well as events following randomization were excluded from the analysis, which he says is an improper technique.

Packer’s take is that this trial is too flawed to be actionable.

I don’t completely agree.

Although, I should have been more rigorous in mentioning these flaws, CASTLE-AF is not an outlier. It goes in the same direction as previous smaller trials, which also suggested benefit for AF ablation over medical therapy in patients with heart failure.

What’s more, CASTLE-AF deals with a super-select group of patients. These were relatively young (64 years) men with only moderate degrees of heart failure. As the eminent Dr. Richard Lehman writes in his weekly journal round-up, it makes sense that doing ablation rather than giving more of a failed medical therapy produced better outcomes.

CASTLE-AF does not apply to the vast majority patients who come to the hospital with AF and heart failure. The typical patient we see with heart failure and AF are older, frailer, often female, and burdened with many other organ issues.

It would be a tragedy if electrophysiologists used CASTLE-AF results to do procedures on these sorts of patients.

I don’t think that will happen.

A different Dr. Packer, Dr. Douglas Packer, from Mayo Clinic, will likely present results of another AF-ablation outcomes trial later this year. It’s called the CABANA trial, and it will look at outcomes in a more typical group of patients who undergo AF ablation. I look forward to these results.

I’ve learned from this experience.

JMM

Thoughts on the Apple Watch and Mobile ECG

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Last week I wrote a column on theheart.org | Medscape Cardiology on the new Apple Watch ECG and Kardia Band.

The Tweet I sent out on Saturday has done well — 74 Retweets (without any robots) is pretty good.

Here is an overview of some of the points I made in the column.

One is that Apple’s interest in AF is huge. The company has partnered with Stanford researches and has started the Apple Heart Study. Any owner of an Apple Watch can volunteer to participate.

The excitement of mobile ECG technology is that it allows for rhythm screening–mostly AF. The thinking: stroke is a major health problem; AF associates with stroke and we have treatments (anticoagulants). Thus it would be good to know one’s heart rhythm.

You know how simple thinking about screening works in medicine. Yes, there are snags. One problem now is accuracy. In the column, I attached two AliveCor tracings that mistakenly labeled premature beats as AF. Both patients suffered anxiety from the fake AF.

I did list many upsides of mobile ECG technology.

  • Marc Cuban himself tweeted on my timeline that he had AF and likes the peace of mind of knowing what his rhythm is.
  • A man from Romania, where access to doctors is less than it is here, made the point that mobile ECGs allowed him to get faster responses from doctors.
  • My friend Dr. Gopi Dandumudi from IU believes that empowering consumers to be involved in their healthcare is a good thing in the long run.
  • And I have often prescribed the AliveCor to confirm diagnoses and monitor for side effects from drugs.

Indeed the device is useful for specific tasks.

Of course, its proponents (and marketing team) hype it as a revolutionary tool for health. This may be true someday, but I have many concerns in the interim.

Here are four challenges.

One is that the causal link between AF episodes and stroke is less certain than you may think. This argument gets complicated. There was once a researcher named Bradford Hill who came up with nine criteria that should be fulfilled if one factor is thought to cause another.

AF does fulfill some of these criteria, but it clearly does not fulfill others. For instance, one of Hill’s criteria is correlation in time. AF fails this criteria because there are multiple studies showing poor correlation between the timing of AF episodes and stroke event. (I explain more in the column.)

Another challenge is that we don’t whether clot-blocking drugs (anticoagulants) will benefit patients with shorter-lived or non-symptomatic AF (EPs say subclinical AF) in the same way it does those patients with longer-lasting or symptomatic AF. The studies showing anticoagulant benefit were done in people with clinical AF or AF seen on multiple, regular in-office ECGs.

The reasons to doubt anticoagulants will benefit many of the people with short-lived AF is that plenty of studies observe very low untreated stroke rates in these patients. That is key because it’s hard for any treatment to lower an already low event rate. Remember, too, anticoagulants don’t come free: they do increase the risk of bleeding. No doubt these drugs are beneficial in higher stroke-risk patients, but the mobile ECG will greatly expand the pool of lower-risk people.

The most scary challenge of the mobile ECG is that the greater numbers of AF diagnoses will occur in a US healthcare system that pays hospitals and doctors to test and treat. If you combine fee-for-service payment models and most doctors’ fear of anything heart related, it’s easy to predict a massive increase in overtreatment and overdiagnosis. Think here of the children’s book: If you give a mouse a cookie. Proponents rightly point out that this problem is not the fault of technology.

Finally, the big problem with any new technology is its ability to distract us. Here I believe the distraction is from already proven ways to prevent stroke: read the article. I explain what those are.

JMM

The Nobel in Economics and Medicine?

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Once again, the Nobel prize for economics–not science and medicine–has immense influence on the practice of medicine.

Every day, in fact.

This year, Richard Thaler, a behavioral economist at the University of Chicago, won for his work on human biases and temptations.

The famous writer Michael Lewis (Moneyball) has a nice essay on Thaler’s work here.

Along with Kahneman and Tvresky, the work of behavioral psychologists and economists directly relates to clinical medicine because it describes human decision making.

Thaler made lists of irrational decisions. For example, we often make choices that don’t result in long-term well-being. E.g. Eating sugary foods and obesity. This led him and colleague Cass Sunstein to the concept of choice architecture.

This concept, applied to employee savings programs, led to an increase in the savings rate of workers.

Thaler calls it a sort of libertarian paternalism.

That’s sort of what doctors do, isn’t it? We are experts in medical science; patients are expert in their goals, and the best medical decisions come when we help align care with a person’s goals.

Libertarian paternalism: freedom of choice with expert nudges.

What’s critical for doctors to understand–and I wrestle with this everyday in the office–is that humans are not maximizers, or logical, or even all that sensible. Doctors feel decisions. So do our patients.

Kahneman and Tversky described the notion that people respond differently when a choice was framed as a loss than when it was framed as a gain. As Lewis writes: “tell a person that he had a 95 percent chance of surviving some medical procedure and he was far more likely to submit to it than if you told him he had a 5 percent chance of dying.”

In my earlier years as a physician, I would emphasize the 95% chance things would go well. Now, as I have aged and seen more of what Nassim Taleb calls iatrogenics (medical harm), I find myself more often feeling the potential harm. (I’m reading Taleb’s book Antifragile. It’s really good.)

Then I am thinking to myself: how I feel about this decision determines the framing.  And that will surely influence the patient. Gosh. This behavioral psychology stuff is damn important.

If I am too pessimistic, patients might lose out on the gain. If I am too optimistic, patients can be exposed to needless harm.

Take the decision to implant an ICD for prevention of sudden cardiac death.

The accepted benefits in selected patients is an absolute risk reduction of about 7%. That’s pretty good. It corresponds to an NNT (number needed to treat) of about 14–meaning, you have to implant 14 ICDs to save one life. We can’t know who the 13 are who won’t need it, and who the one is who will have his life extended.

But all treatment comes with potential harms. A recent look at real-world data suggests complications of ICDs occur in about 7% of people.

How do I frame this? What if the day before this visit, I had a patient suffer a massive complication from an ICD? Or perhaps the day before, a person was saved from death with an appropriate shock.

 

Medical decisions are not so easy. Because, humans, as Thaler has found, are complicated. Thinking about how we humans think is one of the most interesting aspects of this job.

JMM

Inflammation, Ablation, Fats, LDL, etc .. My review of ESC 2017

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The European Cardiology Congress, ESC as it is called, has grown into the largest medical meeting in the world. This year, more than 31,000 attendees from 153 countries came to Barcelona.

I was busy. Here is an update of the big stories:

Inflammation: 

Experts agree that inflammation associates with heart disease. One of the keys to showing inflammation causes heart disease would be to show a reduction of cardiac events with a drug that blocks inflammation.

The CANTOS trial tested the ability of a drug called canukinumab, which is already approved for rare causes of inflammatory diseases, to reduce cardiac events. Canukinumab exerts its anti-inflammation action by blocking a key signaling chemical in the inflammation cascade.

CANTOS turned out positive–well, sort of. Patients who took canukinumab had a 15% reduction of cardiac events. That sounds like a lot but translates to an absolute reduction of 0.64%. Researchers noted two other important observations: one was that blocking inflammation led to a small rise in fatal infections. The other nifty observation was that patients on canukinumab died from cancer at a lower rate than those on placebo. This anti-cancer effect will be explored further.

My post on CANTOS is here: Quick Thoughts on the CANTOS Trial

AF Ablation: 

The CASTLE-AF trial studied the effect of AF ablation in patients with advanced heart failure–patients had low ejection fraction and ICDs. Does ablation in these patients reduce death rates or hospital admissions? The preliminary answer was yes. (Preliminary because the trial has not yet been published.)

Investigators reported a lowering of death rate by 47%. That’s massive. Many drugs and ICDs have been shown to lower death rates in patients with heart failure, but the reductions range from 15-35%.

The published results of this trial will be novel and could change the view of AF ablation. Novel because, to date, AF ablation has only been shown to improve quality of life–not outcomes. One strong warning is that patients included in CASTLE-AF were highly selected, most had previously failed antiarrhythmic drugs and the centers doing the ablation were highly experienced. I worry that irrational exuberance at the time of trial publication will add to the overuse of AF ablation that already exists.

My Post on Castle AF is here:  CASTLE-AF: Does It Change the World of AF Ablation?

New Use of Rivaroxaban (Xarelto):

The drug rivaroxaban (Xarelto) has become well-established for prevention of stroke in patients with AF. At ESC, a huge trial called COMPASS tested lower doses of rivaroxaban for the prevention of cardiac events (heart attack, stroke, death) in patients with established heart disease. We call this secondary prevention.

Showing improvement in secondary prevention in 2017 is hard because we have so many good treatments already.

The COMPASS trial showed that the combination of low-dose rivaroxaban (2.5 mg twice daily) plus aspirin lowered the event rate by a mere 1.3%. And this gain was countered by a 1.2% rise in major bleeding. Though this sounds like a wash, experts from around mainstream cardiology lauded the results. The king of cardiology, Dr. Eugene Braunwald, from Harvard, provided the discussion in the main auditorium after the trial was presented. He embraced the results as a breakthrough.

I was not so embracing. My post on COMPASS is here: The COMPASS Trial: Time for Clear Heads, Not Celebration

Extremely Low Cholesterol Levels:

You may have heard about the new cholesterol-lowering drugs called proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor drugs. These 14,000$ per year injections cause dramatic drops in LDL–the bad cholesterol. In the previously published FOURIER trial, patients on PCSK9i drugs had a lower rate of cardiac events, but surprisingly, the reduction in nonfatal events did not translate to improved death rates.

At ESC, the authors of FOURIER presented a sub-analysis of the results looking specifically at the association of LDL and cardiac events as well as safety. (Extremely low levels of cholesterol raise concern about other bodily functions.)

Three findings emerged: one is that many patients in the trial achieved crazy-low LDL levels, some in the single digits! The second finding was that the lower the LDL, the lower the event rate. The third finding was that despite crazy-low levels of LDL, the investigators noted no safety issues.

One popular narrative from these observations is that LDL in the blood is toxic and should be removed. In my post, titled, FOURIER: Very Low LDL-C Post Hoc Analysis Doesn’t Move the Needle, I make the case that this evidence is not enough to change our thinking about these expensive drugs. And, since the trial was truncated after only 2 years, it’s hard to say much about safety. Remember, people don’t take cholesterol-drugs for only two years.

The Healthiest Diet? 

The debate on which diet and which percentage of nutrients, say fat, carbohydrates, plants, etc rages on. At ESC, results of massive observational study of more than 130,000 people across Earth, found that carbohydrates to be a villain, and fat intake, even saturated fat, associated with better outcomes. The PURE study, which included not one but three papers, was published in the Lancet.

One aspect of PURE is that it flies in the face of recommendations from our American Heart Association. My colleague Sue Hughes has great coverage of this story here: PURE Shakes Up Nutritional Field: Finds High Fat Intake Beneficial

Sue’s story includes this beautiful quote from senior researcher Dr. Salim Yusuf:

My hope is that our results will stop the whole population from feeling guilty if they eat fat in moderation. While very high fat intake—when it accounts for 40% or more of your dietary intake—may be bad, the average fat intake is about 30% and that’s okay. We’re all afraid of saturated fat, but actually we shouldn’t be. Saturated fat in moderation actually appears good for you.

Miscellaneous: 

I recapped these stories in my weekly podcast called This Week in Cardiology. 

I also gave my Watchman debate. I think I did pretty well as the antagonist. My opponent, Prof Horst Sievert was strong. He made mention that my case against Watchman came from a blog–but I countered that it has, in fact, been peer-reviewed and accepted for publication in a major journal. Stay tuned for more. Readers … stay suspicious of left atrial appendage closure.

Only a week after the terror tragedy, Barcelona felt like the safest city I have been in. If anything, given the tone at the meeting and on the streets, the terror event seemed to create greater cohesiveness of the people.

JMM