Rapid IV sotalol loading feasible, safe for AF patients

IV sotalol administered rapidly as a loading dose to initiate oral sotalol therapy is feasible and safe for rhythm control in individuals with atrial fibrillation (AF), the DASH-AF study finds.

“Rapid IV sotalol loading (RIVL) is feasible and safe, has lesser risk of significant QTc prolongation, requires less frequent dose adjustments and [shorter hospital] stay, and is less expensive than conventional loading (CL),” said Dr Dhanunjaya Lakkireddy from The Kansas City Heart Rhythm Institute, Overland Park, Kansas, US, at AHA 2022.

Compared with CL, RIVL had a trend towards lower ΔQTc change at completion-baseline of drug loading (20.4 vs 25.0 ms; p=0.11) and significantly lower need for dose adjustment (4 percent vs 17 percent; odds ratio [OR], 0.22; p=0.003). [AHA 2022, Session FS.03]

There was also a numerically lower trend towards severe bradycardia and QTc prolongation leading to drug discontinuation with RIVL vs CL (3.3 percent vs 5.8 percent; OR, 0.56; p=0.36).

The DASH-AF team evaluated 240 patients with symptomatic AF who were scheduled to undergo sotalol therapy and those who have had AF ablation, were stable, and in sinus rhythm for an hour post-procedure prior to IV sotalol initiation. In the RIVL arm (n=120; mean age 68.2 years, 63 percent male), patients were loaded with IV sotalol equivalent to the selected oral dose (80 or 120 mg) for over an hour. Four hours thereafter, an oral dose was given if QTc is acceptable. Patients were discharged home if QTc remains acceptable 2 hours after the first oral dose. In the CL arm (mean age 65.6 years, 60.8 percent male), 120 patients admitted for oral loading received the usual five doses (80, 120, or 160 mg) Q12H.

Conduction system-related side effects, cost analysis

No TdP* cases were reported with RIVL, while there was one case with CL. Sotalol was stopped in 3.3 percent of participants on RIVL; the rate was nearly twice as high in the CL arm (5.8 percent).

There were no significant differences between the RIVL and CL arms in terms of EKG parameters, both at baseline (435.2 vs 449.0 ms [QTc duration] and 73.2 vs 75.0 bpm [heart rate]) and at completion (448.7 vs 460.9 ms and 69.5 vs 70.0 bpm, respectively).

Whisker plots also showed comparable QTc intervals, ΔQTcs, QTc trends, and heart rate trends between arms, “clearly suggesting that there was no significant bradycardia, conduction system abnormalities, or any other major ventricular arrhythmias that were concerning,” noted Lakkireddy.

Average cost per admission was markedly lower with RIVL than CL (5,068 vs 8,569 USD). “When you extrapolate this to 100 admissions, this cost mounts easily,” he said.

A paradigm shift in practice?

In 2020, the US FDA approved the use of IV sotalol to help initiate oral sotalol, based on MIDDP**. “[This approval] offered an opportunity to rapidly load sotalol to achieve steady state and achieve maximum QTc within 6 hours, resulting in significant reduction in hospital stay,” explained Lakkireddy.

However, the lack of randomization and small sample size may have limited the findings, he pointed out. “We did not check for efficacy of the AF rhythm control with sotalol as this was not the endpoint we were worried about. [Also,] we only included patients with preserved renal function. Hence, caution is advised when extrapolating the results in patients with renal disease.”

“[Nonetheless, our results show that RIVL] could improve patient convenience and reduce hospital stay, resource consumption, and overall healthcare costs, especially during and in the aftermath of the COVID-19 pandemic,” concluded Lakkireddy. “[Our findings] could thus bring in a paradigm shift in our clinical practice, allowing patients for rapid discharge.”