What’s the best medicine for treating AF?
Now that is a frequently asked question.
You already know the answer. But perhaps the obvious deserves a few words?
First, let’s clarify what we are talking about when we use the term AF medicine. I’m speaking here about the so-called anti-arrhythmic drugs. Other names include “membrane-active” or “rhythm-control” medicines. These are the drugs that act directly on the electrical properties of atrial muscle cells. The most common ones are listed here:
- Type IC-drugs: propafenone and flecainide
- Type III drugs: sotalol and dofetilide.
- Multi-channel blocking drugs: dronedarone and amiodarone
For the purposes of this post, let’s exclude anticoagulants (blood thinners) and the drugs that slow the ventricular rate (pulse) of AF. The so-called “rate-control” medicines act almost exclusively on the AV node—the connection between the atria and ventricle. Beta-blockers (metoprolol, carvedilol), calcium channel blockers (diltiazem, verapamil) and digoxin slow the rate of AF by slowing conduction of AF impulses through the AV node. They rarely suppress AF.
So let’s talk about AF suppressing drugs. First the disease AF:
One major rule of thumb for AF is that there are no rules. The disease is crazy complicated and diverse. It’s more common in older people, but young people get it too. It begets itself, but can also go just go away. AF is more common in patients with obesity and high blood pressure, but thin patients with low blood pressure also get it. Some patients fibrillate for years and never know it, while others are incapacitated by only brief episodes. Older patients with advanced heart disease can deteriorate rapidly with AF, and they benefit from emergency treatment. But for the majority of AF patients, such emergency treatment increases the risk of over-treatment.
At the start of my career, AF was easy to treat. There were hardly any medicines and ablation therapies had not yet been thought of as possible. AF patients mostly had to live with the disease. Our lack of tools meant there wasn’t a need for AF specialists and electrophysiologists. Fortunately that’s all changed now.
If you think AF is tough to figure out, let me tell you about anti-arrhythmic medicines. What a paradox.
There are three major problems with AF medicines:
Lack of Efficacy: The most recent trial comparing AF medicines to ablation revealed that 72% of patients in the medical arm had AF recurrences. Admittedly, using just 30 seconds of AF as the threshold for treatment failure is overly rigorous, but the fact remains that rhythm-control medicines fail more times than they work. They rarely eliminate all episodes of AF and rarely do they work over the long-term. In fact, when a patient who is taking an AF-drug reports being free of AF for years, I question whether it’s the drug or perhaps the AF is gone.
Pro-arrhythmia: All of the rhythm-control medicines can actually cause arrhythmia. We call this pro-arrhythmia. And no, that’s not a typo. Rhythm-control AF medicines harbor the potential to make things worse. Much worse. Take these vignettes:
Examples of pro-arrhythmia range from mild to fatal. In mild cases, many of the rhythm-control medicines predispose to, unmask or exacerbate low heart rates (bradycardia). This gets bumped to moderate when pacemakers are implanted to treat drug-related slowing. Other moderate examples of pro-arrhythmia include the properties of conduction slowing drugs like propafenone and flecainide. In some cases the drug suppresses AF; but in other cases the slowing effect converts AF to Aflutter—a slower more organized, but equally troublesome arrhythmia. And no, you cannot tell when this will happen or in whom.
The most severe pro-arrhythmia from AF drugs comes when drugs that prolong duration of activation (action potential), like sotalol and dofetilide cause QT interval prolongation. (The QT interval can be measured on an ECG.) If QT prolongation goes unchecked, ventricular tachycardia (torsades de pointes) can occur. This predisposes the AF patient to sudden death. One of my first lectures in training reviewed a famous study of the old drug quinidine. Researchers found that quinidine reduced the burden of AF, but at the cost of an increased risk of death.
That’s the paradox: the same drug that can help can also cause harm. It’s always been this way for rhythm drugs.
Side Effects: In their tendency to cause side effects, rhythm-control medicines are no different from all other drugs. Fatigue, GI intolerance, blurred vision, funny taste in the mouth, and balance issues are all side effects that can occur with these drugs. Again the tradeoff: a patient that feels their AF is suppressed with, say propafenone, has to decide if the metallic taste is better than having episodes of AF. Tradeoffs. Treating disease is always about tradeoffs.
That’s why it is better to prevent preventable disease.
In the next post, I’ll explore the factors that go into choosing AF drugs.