Electrical storm beta-blocker choice (Chatzidou 2018)

I started this week with a resuscitation plan for the patient who presents in electrical storm. I wanted to follow that up with a little evidence based medicine. This is an interesting RCT looking at electrical storm beta-blocker choice, comparing propranolol to metoprolol.

The paper

Chatzidou S, Kontogiannis C, Tsilimigras DI, et al. Propranolol Versus Metoprolol for Treatment of Electrical Storm in Patients With Implantable Cardioverter-Defibrillator Journal of the American College of Cardiology. 2018; 71(17):1897-1906. DOI: 10.1016/j.jacc.2018.02.056

The Methods

This is a single center, randomized, controlled trial.

Patients

All patients with electrical storm (defined as 3 or more episodes of ventricular tachycardia or ventricular fibrillation, separated by at least 5 minutes, within a 24 hour period and resulting in a device intervention).

Excluded: Drug induced arrhythmias, arrythias secondary to MI or acute heart failure, prolonged QT interval, hypokalemia, renal impairment, or a systolic blood pressure <90.

All patients were on an amiodarone infusion.

Intervention

Propranolol 40 mg orally every 6 hours for 24 hours.

Comparison

Metoprolol 50 mg orally every 6 hours for 24 hours.

Outcome

The primary endpoint was the time to the last occurrence of an arrhythmic event (VT or VF) requiring ICD intervention for termination.

The Results

They enrolled 60 patients over 6 years.

The time to termination of electrical storm was 3 hours with propranolol versus 18 hours with metoprolol.

Propranolol was associated with a 2.67 fold (adjusted) decrease in Vtach and Vfib across the 48 hour study period.

My thoughts

As a rule, I generally assume that all medications within a class of drugs will be equally efficacious. Overall, this rule holds up surprisingly well. Sure, when a brand new (generally expensive) drug hits the market, there will almost always be a manufacturer supported trial that concludes that it is better than its competitors. However, when the competitor runs their own trial, it turns out that their drug is better. Ignoring this back and forth “marketing science”, most drugs within a class generally end up being equivalent. (As an aside, I think the evidence indicates that all thrombolytics are equally efficacious in ischemic stroke. There is nothing special about tPa.)

However, I supposed it depends on how you define a class of drugs. Most of the time, novel drugs within a class are just playing on slightly altered pharmacokinetics, or very minor alterations, that sound good in theory, but are ultimately meaningless when thrown into the complex and finely tuned homeostasis that is the human body. However, sometimes we use a single label for drugs that act on very different receptors in the body. Beta-blockers, because they interact with different beta-receptors, might be one of the rare occasions when it is important to select the right agent within the class.

In this trial, there is a marked difference between propranolol and metoprolol. Outcomes were clearly better with propranolol. The trial is small, and single centered, but I think it represents an important piece of science that will change my practice.

Some people might wonder why, given this RCT evidence for propranolol, I suggested using esmolol in the initial management of electrical storm? I will admit, it is possible that I am making a mistake. It is possible that I am getting caught up in the hype for the newer (and much more expensive) esmolol. However, evidence based medicine is not about blindly following RCTs. It is about interpreting the results of those RCTs in the context of your own expertise, as well as incorporating patient values.

In this trial, they slowly loaded oral propranolol over 24 hours. These were relatively stable patients and there was no rush to treat.  The blog post earlier this week was focusing on the critically ill patient that requires immediate intervention. I think that is an important distinction. It is much harder to judge a patient’s hemodynamics in the first hour of their presentation. Every emergency provider has seen a patient’s blood pressure drop precipitously after starting a new medication. In my mind, it makes a lot of sense, at least during the early minutes of resuscitation, to use a medication that can be turned off if the patient gets worse.

That being said, based on this RCT, as soon as I think the patient is stable enough to be transitioned to oral medications, I will transition my patients from IV esmolol to PO propranolol

Bottom line

Propranolol terminated electrical storm faster than metoprolol in this small RCT.

Other FOAMed

I am not smart enough to explain the pharmacological differences between metoprolol and propranolol. If you want to read a great post that gets into a little more details, see this post on EMCrit by Kristina Kipp.

The full post on electrical storm can be found here.

References

Chatzidou S, Kontogiannis C, Tsilimigras DI, et al. Propranolol Versus Metoprolol for Treatment of Electrical Storm in Patients With Implantable Cardioverter-Defibrillator Journal of the American College of Cardiology. 2018; 71(17):1897-1906. DOI: 10.1016/j.jacc.2018.02.056