Key result
In a retrospective review of 189 patients admitted for dofetilide initiation, 49% experienced deviations from the manufacturer-recommended protocol, most frequently due to a prolonged baseline QTc.
Why the study?
Outcomes of deviating from the manufacturer-provided dofetilide initiation algorithm had not been reported outside of clinical trials.
Does deviation from the standard dofetilide initiation protocol increase adverse events in patients requiring dofetilide?
Observational (n=189)
No
Does deviation from the standard dofetilide initiation protocol increase adverse events in patients requiring dofetilide?
In real-world practice, deviations from the FDA-mandated dofetilide initiation protocol are common (49%) and may be associated with a numerically higher rate of serious adverse events.
May indicate gaps in dofetilide initiation protocols; leaves open whether deviations increase adverse events.
BACKGROUND: Manufacturer/federal drug administration (FDA) recommends inpatient initiation of dofetilide with the manufacturer providing an initiation algorithm. The outcomes of algorithm deviation have not been reported outside of clinical trials. OBJECTIVE: We sought to perform a chart review of all the patients admitted for inpatient initiation of dofetilide to report on the incidence of protocol deviations and their implications. METHODS: We performed a retrospective review of all patients over a 15-month periodwho were initiated on dofetilide for the very first time or reinitiated on dofetilide after a break of three months or more at our institution. We assessed data about patients who were given dofetilide without adherence to the protocol (i.e. protocol deviation). RESULTS: A total of 189 patients were included in the study with a median age of 66 ± 9 years. Mean baseline QTc interval was 436 ± 32 msec, and 61% (116/189) were in atrial fibrillation (AF) at the time of dofetilide initiation. In 9% (17/189) of patients, the drug was discontinued due to intolerance or inefficacy. Therapy in 49% (93/189) of patients was noted to deviate from manufacturer recommended protocol with deviations more than once in some patients during the same hospitalization. Baseline QTc exceeding 440 msec(>500msec in conduction abnormalities) was the most frequent deviation (25%; 47/189).Ventricular tachyarrhythmia occurred in 4% (7/189) of patients, did not differ between patients, and occurred with and without protocol deviations (5% vs 2%; p = 0.27). CONCLUSIONS: In our retrospective study, there were frequent deviations from the manufacturer-recommended algorithm guidelines for dofetilideinitation, primarily due to prolonged baseline QTc interval. The impact of these protocol deviations on drug discontinuation was uncertain; however, significant adverse events were higher in the deviation group compared to the group that fully adhered to the protocol. Further multicenter studies are warranted to clarify our findings.
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Dar et al. (2019) conducted an observational in Atrial fibrillation (n=189). Deviation from FDA-recommended dofetilide initiation protocol vs. Adherence to protocol was evaluated on Incidence of deviations from FDA-recommended protocol for inpatient dofetilide initiation. In a retrospective review of 189 patients admitted for dofetilide initiation, 49% experienced deviations from the manufacturer-recommended protocol, most frequently due to a prolonged baseline QTc.
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