Effect of fingolimod on cardiac autonomic regulation in patients with multiple sclerosis

Abstract

Background:

Fingolimod modulates sphingosine-1-phosphate receptors that are also found in cardiovascular tissue.

Objective:

To investigate the effects of fingolimod on cardiac autonomic regulation prospectively.

Methods:

Twenty-seven relapsing–remitting multiple sclerosis patients underwent 24-hour electrocardiogram recording before, at the first day of fingolimod treatment (1d) and after three months of continuous dosing (3mo). The time interval between two consecutive R-peaks (RR-interval) was measured. Cardiac autonomic regulation was assessed by the various parameters of heart rate variability. Parasympathetic stimulation prolongs the RR-interval and increases heart rate variability while the effects of sympathetic stimulation are mainly the opposite. The low frequency/high frequency ratio reflects sympathovagal balance.

Results:

From baseline to 1d, a prolongation of the RR-interval (P<0.001), an increase in the values of various heart rate variability parameters (P<0.05 to P<0.001) and a decrease in the low frequency/high frequency ratio (P<0.05) were demonstrated. At 3mo, although the RR-interval remained longer (P<0.01), the values of various heart rate variability parameters were lower (P<0.01 to P<0.001) as compared to baseline. At 3mo, the low frequency/high frequency ratio (P<0.05) was higher in men than in women although no such difference was found at baseline or at 1d.

Conclusions:

After an initial increase in parasympathetic regulation, continuous fingolimod dosing shifts cardiac autonomic regulation towards sympathetic predominance, especially in men. Careful follow-up of fingolimod-treated relapsing–remitting multiple sclerosis patients is warranted as sympathetic predominance associates generally with impaired outcome.

ClinicalTrials.cov: NCT01704183