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at time of writing, Adult Internal Medicine Pharmacy Resident, Virginia Commonwealth University, MCV Campus, Richmond, VA; now, Clinical Pharmacist, Martha Jefferson Hospital, Charlottesville, VA
Associate Professor of Pharmacy and Medicine, Virginia Commonwealth University, MCV Campus
Reprints: Michael A Crouch PharmD BCPS, Virginia Commonwealth University, MCV Campus, 410 N. 12th St., PO Box 980533, Richmond, VA 23298-0533, fax 804/828-8359, macrouch{at}vcu.edu
BACKGROUND: Dofetilide gained Food and Drug Administration approval for persistent atrial fibrillation/flutter (AFF) based on 2 randomized, placebo-controlled, dose-ranging studies. Concerns of proarrhythmia have prompted the manufacturer to develop specific treatment guidelines.
OBJECTIVE: To determine the effectiveness and safety of dofetilide in clinical practice as well as to ascertain whether clinicians are following established dosing guidelines.
METHODS: This retrospective analysis evaluated guideline
adherence and safety in patients who received dofetilide at a tertiary care
medical center. Safety assessment included monitoring for the occurrence of
excessive QTc interval prolongation and torsade de pointes. Excessive QTc
interval prolongation was defined as >15% above baseline after the first
dose or >500 msec following any dose (>550 msec in patients with
ventricular conduction abnormalities). Patients were included in the
effectiveness assessment if they received at least 36 hours of dofetilide for
persistent AFF, received an appropriate dose per guidelines, and did not
receive direct current cardioversion during the evaluation period. We compared
the 36-hour conversion rate with dofetilide in this study with that observed
in the EMERALD and SAFIRE-D trials using the Z test, and we evaluated the
incidence of excessive QTc interval prolongation in high-risk subgroups by
2 analysis.
RESULTS: Investigators identified 107 patients. The primary indication for dofetilide was AFF, with 58.9% receiving the drug for paroxysmal disease. Prescribing followed established guidelines, except that it was used intermittently by nonconfirmed prescribers (5.6%) and/or at inconsistent doses (14%). Excessive prolongation of the QTc interval occurred in 17.8% of patients after the first dose and 26.2% during subsequent doses; prolongation was more common in those with structural heart disease (p < 0.01). No patients developed torsade de pointes. In the effectiveness assessment (n = 25), the conversion of persistent AFF at 36 hours was higher than in previous studies (48% vs 27.2%; p = 0.05).
CONCLUSIONS: In clinical practice, the conversion of persistent AFF with dofetilide is at least comparable to premarketing studies, with a similar safety profile. Institutions should continue to emphasize adherence with established treatment guidelines.
Key Words: antiarrhythmic agents, atrial fibrillation, atrial flutter, dofetilide
Published Online, May 25, 2004. www.theannals.com, DOI 10.1345/aph.1D465
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