Dr. John Day, Cardiologist

9 Key Findings of the CABANA Study

No one wants to be on drugs for the rest of their life to treat a heart arrhythmia called atrial fibrillation (Afib).  In a perfect world, you would have a safe and simple procedure that would make it all go away.  In this article, I’m going to share the results of the most important study that has ever been done for atrial fibrillation, the CABANA Study.

Why the CABANA Study Needed to Be Done

Gently placing a small catheter into the heart to treat the areas that are misfiring is a procedure that cardiologists have done regularly for nearly 20 years.  Those of us who have taken care of patients with atrial fibrillation have all seen miracle results.  Patients doomed to a life of atrial fibrillation are suddenly free from this affliction.

In fact, the results have been so striking that we even published our results of 37,908 patients in a 2011 study.  In this study, we showed that the procedure was safe and that it could significantly reduce the risk of premature death, stroke, and dementia from atrial fibrillation.  The only problem was that this study was never randomized.  And because it was never randomized it can’t be considered as “proof” that patients live longer and healthier lives with ablation.

In other words, were these findings in our study because catheter ablation works or did healthier patients somehow opt for ablation more than drugs?  No matter how we looked at the data, the only difference we could find in the ablation patients was that people with atrial fibrillation symptoms were more likely to get an ablation.  Which raises an interesting question…are atrial fibrillation patients with symptoms somehow “healthier” than atrial fibrillation patients without symptoms?

We needed proof from other hospitals that catheter ablation works.  Which is the precise reason why the CABANA Study is so important.  And while we thought we were going to get that proof, instead we just got more questions and more controversy.

Perhaps things will be a bit clearer when the study is finally published.  All we know so far is what was shared from a 15 minute presentation at a recent medical conference…

It Was Hard to Enroll CABANA Study Patients

Before we get to the actual results, the CABANA Study was a hard study to do.  As it is well known from many prior studies that ablation is better at keeping people in rhythm and reducing symptoms, it was hard enroll patients to participate in this study.  I personally met with hundreds and hundreds of atrial fibrillation patients who were not interested in participating in this study because they didn’t want to take drugs.

Thus, enrollment in the CABANA Study was slow and it took much longer to complete that what was previously anticipated.  For anyone who has done clinical research, motivated patients always have the best outcomes.

Right from the start, motivated patients generally were not included in this study.  Or at least that was the case from our hospital which was the number one enrolling hospital in this study.  Pretty much the only people we could enroll were those rare patients who had either never heard about ablation before or were ambivalent about how they wanted to treat their atrial fibrillation.

Cabana Study Results: Intention to Treat

To the scientific purists, you can only analyze a study based on the intent to treat.  For 99% of the studies out there, this approach works.

However, the CABANA Study was different than most other studies.  Hence, the controversy.

Nine percent of the people assigned to an ablation never actually had the procedure.  Nine percent is a big number.  That means more than 100 patients in this study of 2,204 people never got the therapy they were supposed to get.  So, if you are interpreting the results, how do you account for the 9% who were assigned to ablation but didn’t get an ablation?

But that was just the tip of the iceberg.  Of those assigned to take drugs, 28% couldn’t do it.  The CABANA Study required these patients to stick with drugs for five years.

If so many patients didn’t get the treatment they were supposed to get, it makes interpreting the study really difficult.  If you use the “intention to treat” method then you have to ignore the fact that too many patients in the CABANA Study never received the therapy they were supposed to receive.

Per Protocol Analysis: The CABANA Study

Just like you probably wouldn’t give your kids credit for doing the dishes unless they actually do the dishes, do you analyze the results of the CABANA Study in a way where you give credit for a treatment they never received?  If you only believe in giving credit where credit is due, then you probably want to interpret this study based on a per-protocol analysis.

According to the per protocol analysis, you simply see what happened to the people who actually completed the protocol.  In other words, if you had an ablation then it was counted as an ablation.  Likewise, if you took drugs it was counted as taking drugs.

9 Key Findings of the CABANA Study

As I have thought more about how the CABANA Study, I have decided to take myself out of the intention to treat versus per-protocol analysis debate.  Rather, I will show you the results both ways and then let you decide whether you subscribe to the intention to treat or the per-protocol way of interpreting the study.

If you are an intention to treat person, then I’ll give you the results based on how the patients were randomized and we’ll ignore what therapy they actually received.  An if you are a per-protocol person, then I’ll share with you what happened to the 1,307 patients who had an ablation compared to the 897 who were able to stick with the drugs.

1. Ablation Patients Are More Likely to Stay in Rhythm

If your goal is to eliminate atrial fibrillation, then ablation was the clear winner.  Regardless of how you analyze the CABANA Study, there is no controversy when it comes to maintaining rhythm.  Even by handicapping drugs and using an intention to treat analysis, your chances of remaining in normal or sinus rhythm is increased by 47% with an ablation (HR 0.53, CI 0.46-0.61, p<0.0001).

2. The Mortality Benefit Depends on How You Analyze the Data

If you choose the intention to treat methodology, then there was no difference in survival between drugs and ablation.  However, if you choose the per-protocol methodology then the numbers are radically different.

Of those who actually received an ablation, their risk of dying during the study was 40% lower (4.4% vs 7.5%, HR 0.60, P=0.005).  This is a huge mortality reduction and it is right in line with our 2011 study showing the exact same thing.  But then again it begs the question I raised earlier in this article, are atrial fibrillation patients with symptoms somehow healthier than those without symptoms?  Unfortunately, this is a question that has yet to be answered.

3. The Composite End point of Death, Strokes, Bleeding, and Cardiac Arrests Also Depends on How You Analyze the Data

As with the mortality question above, the combined end point of death, strokes, bleeding, and cardiac arrests in the CABANA Study also depends on how you interpret the results.  If you choose intention to treat then there was no meaningful difference.

On the other hand, the primary end point of death, strokes, bleeding, and cardiac arrests of this study was dramatically lowered with ablation.  In fact, those patients who actually got an ablation in this study experienced a 33% lower risk of death, strokes, bleeding, or cardiac arrest (HR 0.67, CI 0.50-0.89, p=0.006).   Once again, these finings are right in line with our 37,000 patient study.

4. Ablations Kept Patients from Getting Hospitalized for Atrial Fibrillation

Regardless of how you interpret the results, the finding was the same.  Ablation did a much better job at keeping atrial fibrillation patients from winding up in the hospital.  And even if you use the intention to treat analysis thereby handicapping ablation, drug patients were 17% more likely to end up in the hospital (HR 0.83, P=0.002).

5. Ablation Patients Had a Better Quality of Life

Although the numbers haven’t been presented yet, the lead investigator of this study, Dr. Doug Packer, shared that ablation patients enjoyed a better quality of life.  This finding came as no surprise and is right in line with just about every other study that has been done.

6. Heart Failure Patients Really Benefited from Ablation

For the sickest patients in this study, those with not only atrial fibrillation but who also had heart failure, did exceptionally well with ablation.  In fact, their risk of death, stroke, bleeding, or cardiac arrest plummeted by 49%!

Of course, to those who follow the latest atrial fibrillation research, this came as no surprise.  A recent study in the prestigious New England Journal of Medicine by Dr. Nassir Marrouche came to the same exact conclusion.

7. Ablation Procedures Are Safe

For me, probably the biggest surprise was how safe ablations have now become.  It should be noted that the CABANA Study was only done in the most experienced centers in the world.  Thus, these results are not applicable to every hospital in the world performing catheter ablation procedures.  However, in the most experienced hands, there were only three strokes, eight tamponades, a couple of vascular events, and no atrial esophageal fistulas in the ablation patients.  As our hospital was the top enrolling site in the US, I can tell you that I personally saw more drug complications than ablation complications in this study.

8. Younger People Did Exceptionally Well with Ablation

As I have said many times on this blog, young and active people like sinus rhythm.  They like using all four chambers of their heart.  Young and active people don’t like the way they feel when their hearts are out of rhythm.

Thus, it should come as no surprise that people under age 65 were much less likely to suffer from death, strokes, bleeding, or cardiac arrests with ablation.  And, based on the results of the CABANA Study, you could make an argument that younger patients should now be offered an ablation as first line treatment for their atrial fibrillation.

9. Minorities Fared Better with Ablation

This is a finding from the CABANA Study that I’m not sure what it means.  For some reason, minority groups fared better with ablation.  Perhaps future studies will shed light on this finding.

Who Shouldn’t Have an Ablation?

Despite the positive findings of ablation in the CABANA Study, there was one group that didn’t do so well with ablation.  For those age 75 and older, medications seem to be the best option (HR 1.54).

Perhaps this group, on average, wasn’t so active.  Thus, sinus rhythm may not have had that much of a benefit.  I suspect that if the CABANA Study could have separated out the active versus sedentary people, they may have found a different result.

How Can You Further Optimize Ablation Results?

For those who want even better ablation results than those reported in the CABANA Study, lifestyle optimization is the answer.  Even though this study didn’t look at lifestyle optimization, countless studies by Dr. Prash Sanders, as well as our own studies, have shown that you can at least double the positive effect of ablation with lifestyle optimization.

By lifestyle optimization, I’m talking about losing any extra weight, exercising daily, optimizing your nutrition, optimizing sleep, optimizing stress levels, etc. Indeed, when it comes to long-term freedom from atrial fibrillation, nothing works better than lifestyle optimization.

In fact, studies show that you can eliminate drugs or procedures in about half of everyone diagnosed with atrial fibrillation just by optimizing your lifestyle.  Thus, before you even consider drugs or procedures, the most critical question to ask is can I reverse this condition naturally?

The Big Picture

In my opinion, the big take away from the CABANA Study is that ablation performed remarkably well.  It is especially an attractive option for the patient with atrial fibrillation symptoms that don’t respond to medications.

Should everyone get an ablation?  Of course not.  If you can’t reverse atrial fibrillation with an optimized lifestyle then it may be a reasonable option.  For those in whom drugs don’t work or cause side effects, then ablation is definitely a logical choice.