Same-Day Sotalol Loading for Atrial Fibrillation

EP Lab Digest. 2022;22(12):4.

Dear Readers,

Oral sotalol is commonly used for rhythm control in patients with recurrent symptomatic atrial fibrillation (AF). The drug is usually initiated in the hospital for the first 5 doses, resulting in a 3-day inpatient stay to monitor for excessive QT prolongation, bradycardia, and ventricular proarrhythmia. In 2020, the FDA approved intravenous (IV) sotalol for use in the United States. The initiation protocol was determined using pharmacologic modeling founded in the knowledge that the degree of QT interval prolongation is proportional to serum drug levels. The initiation protocol involves an infusion over 1 hour while the patient is on telemetry with QTc monitoring every 15 minutes. The loading dose depends on the patient’s renal function and oral dose target. The IV dose is followed by an oral dose 4 hours later, with a second oral dose given the next day 12 hours after the first dose. The QTc is measured every 2-4 hours and after each oral dose. The patient remains in the hospital for another 3-7 hours, resulting in a full day hospital stay.

The IV loading approach shortens the hospital stay from 3 days to 1 day. And, although IV sotalol is more expensive than oral sotalol, a 1-day stay greatly reduces hospital-related expenses and minimizes the need for valuable hospital staffing. However, giving the drug intravenously with frequent QTc measurements is resource intensive, often requiring 1:1 nursing during the infusion. Patients are then admitted to the hospital overnight, which usually means they need to be transferred to a different unit. The IV sotalol loading approach might be preferred by patients and may be in the financial best interest of the hospital, but some hospital administrators struggle to move resources from one venue to another to support the IV infusion. One solution to the resource challenges of the current FDA-approved IV sotalol protocol is to minimize the need for 1:1 staffing during the IV drug infusion, and to discharge the patient the same day after a single oral dose.

During the American Heart Association Scientific Sessions 2022, Dhanunjaya Lakkireddy, MD, presented the results of the Feasibility and Safety of IV Sotalol Administered as a Loading Dose to Initiate Oral Sotalol Therapy (DASH-AF) trial. Their hypothesis was “that the intravenous loading regimen followed by oral sotalol administration 4 hours after the conclusion of the IV infusion (every 12 hours thereafter) will result in sotalol peak concentrations at the end of IV loading dose (IV to oral loading) which are comparable to the steady state and maximum QTc seen on day 3 after the last in-hospital oral dose.”^1,2 They enrolled 120 patients who received a truncated, same-day IV sotalol loading protocol by discharging patients after the first oral dose, and compared their outcomes to 120 historical control patients who had previously undergone conventional oral sotalol initiation in the hospital. The inclusion criteria for IV sotalol was strict and excluded patients with a heart rate <50 beats per minute, creatinine clearance <60 mL/min, ejection fraction <35%, or bundle branch block. All patients were in sinus rhythm at the time of IV sotalol administration, with half of patients having just undergone cardioversion or catheter ablation. The overall outcomes were similar in each group. The IV infusion was stopped in only 4 patients for severe bradycardia or excessive QT prolongation, compared to 7 patients in the control group who had the drug stopped during oral initiation. The only patient to have Torsade de Pointes was in the control group. In the IV group, the QT interval increased after the IV load, but did not continue to increase further after the oral dose was given.

The DASH-AF trial was a relatively small nonrandomized trial and was not powered to detect small differences in ventricular proarrhythmia or mortality during IV sotalol loading compared to oral sotalol initiation. However, these results and others that show that prolongation of the QT interval peaks immediately after IV loading of sotalol demonstrates that an abbreviated version of IV sotalol administration with discharge from the hospital on the same day after one oral dose may be a safe alternative to the conventional 24-hour IV/oral sotalol loading, and even more convenient and cost effective compared to the usual 3-day hospital stay for oral sotalol initiation. 

Disclosures: Dr Knight has served as a paid consultant to AltaThera, manufacturer of IV sotalol. He has also served as a paid consultant to Medtronic, the sponsor of the EV ICD study, served on the EV ICD Steering Committee, and was an investigator in the trial. In addition, he has served as a consultant, speaker, investigator, and/or has received EP fellowship grant support from Abbott, AtriCure, Baylis Medical, Biosense Webster, Biotronik, Boston Scientific, CVRx, Medtronic, Philips, and Sanofi; he has no equity or ownership in any of these companies.

References

1. Feasibility and safety of IV sotalol administered as a loading dose to initiate oral sotalol therapy (DASH-AF). ClinicalTrials.gov. Published January 14, 2022. Accessed November 11, 2022. https://clinicaltrials.gov/ct2/show/NCT04473807

2. Ahmed A, Garg J, Atkins D, et al. Abstract 14826: Single day intravenous sotalol as a loading dose to initiate oral sotalol therapy: is it safe and efficacious? Circulation. 2022;146:A14826. Published 30 Oct 2022.