Let’s talk about some of the factors that go into choosing medicines to suppress AF episodes. We call this “rhythm control.”
In Part 1, I introduced some of the complexities of heart rhythm medicine. In this post, I hope to clarify a few of the many issues that come into play when considering a rhythm control strategy.
Question #1: To treat or not:
The first question to ask is whether it’s wise to attempt rhythm control in the first place. This is a tough concept to grasp. The thinking goes: population studies clearly show that patients with AF have higher risks of adverse outcomes over the long-term. It stands to reason that getting rid of something bad (AF) makes sense. The problem with AF is that we don’t have an easy way to treat the disease. As I talked about in yesterday’s post, AF medicines can create problems. Likewise, catheter ablation of AF is far from being a cure; long-term success rates remain modest and though complications occur less often now, ablating AF is still a big procedure.
If you know one trial about the rhythm control strategy, it should be the AFFIRM trial. The landmark trial was published in the NEJM ten years ago. Investigators studied two different strategies for treating AF. About 2000 patients were enrolled in a rhythm control arm while another 2000 were treated with just rate control. Patients in the rhythm control arm received anti-coagulation (at the discretion of the doctor), anti-arrhythmic drugs and many had cardioversions (No AF ablation back then.) Patients in the rate control arm were left in AF, and received only rate-control drugs and anticoagulants. To the surprise of many, leaving patients in AF was the superior strategy. Though more patients in the rhythm control arm were in regular rhythm, it didn’t matter. There were fewer deaths and hospitalizations in the rate-control arm. Strokes were the same too, only warfarin therapy protected patients from stroke. This trial disproved the widely held idea that preventing AF with medicines would protect patients from bad outcomes associated with AF.
It’s common for me to recommend against rhythm control. Sometimes it’s because the atria are too diseased and rhythm control simply is not possible. Other times it’s because the patient tolerates the AF just fine. And in others, the side effects of the medicines or risk of ablation are worse than the AF. The caveats here are important: just because we aren’t treating the rhythm per se, it is still critical to achieve adequate heart rate control and minimize stroke risk.
Question #2: So why would we even try to control AF episodes?
It’s simple: for many AF patients, the symptoms are terrible. The AFFIRM trial mostly enrolled patients that were minimally symptomatic and could tolerate staying in AF. That’s not the case for many (? most) AF patients. It wouldn’t be the case for younger patients—you wouldn’t want to leave a thirty-year old in AF for the rest of her life. You can’t tell patients incapacitated by AF to grin and bear it. For these patients, it’s worth trying to get them back in rhythm. Doctors are supposed to improve both the quality and quantity of life.
Here the future holds promise. The current problem with rhythm control is the treatment—not the strategy. As catheter ablation becomes safer and more effective, it’s likely that rhythm control will improve outcomes. And of course we can hold out hope that an innovative drug company will come up with a more effective and affordable AF medicine. Even more dreamy: society will grow less rushed and people less inflamed–and then there surely would be less AF.
Question # 3: What are some factors that play into the decision of which rhythm drug to use?
What company does the AF keep? We first ask whether a patient has structural heart disease. In the US, structural heart problems stem most often from coronary heart disease. Other important structural heart problems are hypertrophied hearts (from high blood pressure or hypertrophic cardiomyopathy), valvular heart disease and weakened heart muscle (cardiomyopathy).
Based largely on theoretical concerns and a broad interpretation of the very old CAST trial, propafenone and flecainide are rarely used in patients with significant heart disease. That’s too bad. I recently had a patient doing beautifully on propafenone. He then developed chest pain and underwent a stent. Now he had coronary heart disease. Based on this new diagnosis, we felt compelled to change his AF drug. The two ‘safer’ drugs that we tried did not work. He ended up having a successful AF ablation. But was it necessary to have stopped his first and successful drug? Was it fair to generalize his case to a paper published thirty years ago, before the time of cardiac stents? Some experts doubt the reasoning behind this current dogma. See…it’s complicated.
Another important co-existing problem to consider is kidney and liver function. Rhythm drugs are either metabolized in the liver or excreted by the kidneys. Since rhythm control drugs can be toxic at high levels, it’s important to consider how well a patient will clear them from their system. I’ve had many cases in which a rhythm drug worked beautifully, but then had to be stopped because the patient developed impaired kidney function. (The rhythm drugs sotalol and dofetilide are cleared almost exclusively by the kidneys.)
Then there’s the athlete with AF. Athletes often have incredibly slow heart rates. All rhythm drugs (excluding dofetilide) slow the heart rate. That’s a problem. Another is that those of us who exercise competitively notice small decreases in performance. Again, nearly all rhythm drugs can impair maximal cardiac output. Suffice to say, athletes with AF pose significant challenges to their doctors.
Individual variation: One thing that has become much better known these days is that our DNA determines how we handle medicines. The classic example is propafenone metabolism: a small number of patients (7% of the population) have inherited a sluggish liver enzyme important in drug metabolism. These “poor-metabolizers” require a fraction of the normal dose and risk being over-treated.
Drug metabolism is highly variable and highly heritable. As we learn more about our genes, medical therapy will surely get better. Take this interesting study published this week in the Journal of the American College of Cardiology: Vanderbilt researchers found that a common DNA sequence on chromosome 4 was associated with symptomatic improvement with rhythm control drugs. That’s the future my friends. Show me your DNA card and I’ll help you find the right medicine.
How do heart doctors deal with not knowing how individuals will respond to rhythm drugs? We go slowly; we educate the patient and we look for signs of high drug levels. The cool thing about the simple ECG is that it can show evidence of toxicity of rhythm control drugs—propafenone and flecainide increase the width of the QRS and sotalol and dofetilide increase the QT interval. I look at a lot of ECGs.
Oooh…The word count has just topped 1000. Sorry about that.
In part 3 of AF medicines, I’ll explore five reasons why I still use rhythm control medicines. Look for this at the end of the week.