Results
We identified 59 patients that were suitable for inclusion in our study.
Their baseline demographics and characteristics are summarised in Table
1. Analysis of a resting 12-lead ECG prior to commencing donepezil
treatment was compared to the ECG obtained during their most recent
acute hospital admission and demonstrated evidence of significant
prolongation of the PR, QRS and QT intervals (Table 2). The QT corrected
using Bazett, Fredericia, Framingham and Hodges formulae were also
compared, and all confirmed significant QT prolongation during donepezil
therapy. Analysis using the QT nomogram revealed that 8 (13.6%)
patients (3 male and 5 female) went from low arrhythmogenic risk to high
while on donepezil therapy (Figure 1). No significant change in mean HR
was noted; although one patient had donepezil ceased on admission due to
bradycardia and intermittent complete heart block. Cessation of
donepezil resulted in normalisation of this patient’s heart rate and
resolution of their heart block.
Assessment of the effect of donepezil on ECG parameters demonstrated
that males experienced a significantly greater increase in their
corrected QT intervals compared to females (Table 3). There were no
significant differences in all ECG parameters when comparing donepezil
doses (Table 4). Although there was a significant difference in QT
interval between the different treatment duration groups, no significant
difference was found once QT intervals were corrected. Duration of
donepezil therapy did not affect the HR, PR interval or QRS interval
(Table 5).
Point-biserial correlation found that concomitant use of rate-limiting
calcium channel blockers was associated with significant PR prolongation
(r pb = 0.314, P=0.030), while beta-blockers in
combination with donepezil were found to significantly reduce the HR
(r pb =0.256, P=0.050). All corrected QT intervals
whilst on donepezil were significantly prolonged by the use of tricyclic
antidepressants (QTcB: r pb = 0.344, P=0.008,
QTcFred: r pb = 0.382, P=0.003, QTcFram:r pb = 0.379, P=0.003, QTcH:r pb = 0.352, P=0.006). There was no significant
correlation between cardiac comorbidities and changes in ECG parameters.