Episode 86- Why is my patient on two beta-blockers?

Hello and welcome to Episode 86 of ER-Rx- a podcast tailored to your clinical needs. I’m your host, Adis Keric, and in this Pharmacy Consult episode we ask the question; Is it ever clinically indicated to have a patient on two beta-blockers?

One indication to be on any beta-blocker is heart failure with reduced ejection fraction. Guideline-recommended management involves combination therapy of a beta-blocker with a renin-angiotensin system inhibitor- using things like ACE- Inhibitors, ARBs, or an angiotensin-receptor-neprilysin inhibitors – along with as needed diuretics for volume overload.

The benefits of ACE-Inhibitors in HF is a class effect, meaning that any ACE-Inhibitor can be used. For ARBS, guidelines prefer using those with direct evidence of benefit, like candesartan and valsartan, although losartan is still used. For beta-blockers, only three agents have shown benefit. Those include carvedilol (both the immediate and the extended-release products), bisoprolol, and the extended-release metoprolol succinate (metoprolol XL).

In addition to meds, some patients with heart failure have an ICD placed to prevent sudden cardiac death from sustained VT/ VF. A common complication of ICDs is that they can give patients inappropriate shocks- which as you can imagine is super uncomfortable and very scary. To help prevent inappropriate shocks, and reduce the number of appropriate shocks, we can give drugs sotalol. Sotalol can reduce inappropriate shocks by 60%, and appropriate shocks by 40%. Sotalol can also be used as primary therapy in patients who don’t want or can’t have an ICD. But the kicker is that other beta-blockers, including the ones recommended for heart failure- don’t work well for the indication of reducing shocks in patients with ICDs.

So let’s take a second to talk about sotalol. If you remember your Vaughan-Williams classification systems, sotalol is actually a Class III, potassium-channel blocking agent. But it also has Class II, non-selective beta-blocking activity, and it has distinct actions depending on what dose you give. In patients with normal kidney function, a dose of 40 mg BID gives you mostly beta-blocking effects, plateauing after a daily dose of 240 mg. But its potassium-channel blocking effects don’t start until you get to a dose of 80 mg BID and then they increase linearly as you increase the dose. Even more fun is the fact that these different actions come from different isomers of the drug. The L-isomer is responsible for the beta-blocking effects, and the antiarrhythmic effects come from both the D and the L-isomers. If you’re curious, in the US, we carry the racemic (D, L-sotalol) oral formulation.

But you’ll recall that sotalol isn’t one of the three recommended beta-blockers we use in heart failure. This is because we have data showing it isn’t as effective in reducing mortality as the other recommended beta-blockers—some guesses as to why include its hydrophilicity and that special anti-arrhythmic that it has.

On the flip side, we also know that the other beta-blockers recommended in heart failure don’t reduce the risk of shocks in patients with ICDs as well as sotalol does- again, likely due to sotalol’s added antiarrhythmic effects.

In a nutshell, there is a small group of patients with heart failure who also have an ICD, are already on a guideline-recommended beta-blocker, but also have an indication for sotalol. So, in these patients, it is okay to be on two beta-blockers- as long as they have a documented reason from a cardiologist or an electrophysiologist to be on both.

I know that having a patient on two beta-blockers can be scary. But we know from clinical trials that combination therapy of sotalol plus a second beta-blocker doesn’t increase mortality, nor does it reduce the ejection fraction. The only thing we should be on the look-out for is the risk of bradycardia and hypotension- which according to the little data we have should only occur in somewhere around < 15% of patients. And if it does happen, we can adjust the dose of the sotalol and/or the second beta-blocker.

To wrap up- you may sometimes see patients on two beta-blockers- and this wouldn’t be a reason to panic- as long as one of the beta-blockers is sotalol- because sotalol isn’t just a beta-blocker. In the heart failure patient who also has an ICD, the evidence shows that it is appropriate to add sotalol to a heart failure regimen already including a beta-blocker, as opposed to replacing one of the beta-blockers with sotalol. This is because sotalol doesn’t have the same mortality benefit in heart failure as the other agents do, and conversely, the other beta-blocking agents just don’t have the same benefit in reducing shocks in patients with ICDs.

As always, thank you so much for your time, and thank you for wanting to learn more about pharmacotherapy. If you have any comments or anything you’d like to add to this episode, please give me a shout out on the @errxpodcast Instagram page, or reach out to me on errxpodcast.com- I’d love to respond to all comments and criticisms.

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