Disorders of sleep and wakefulness associated with excessive sleepiness are also associated with increased cardiovascular risk. Because modafinil is an emerging treatment to promote wakefulness, we evaluated its cardiovascular safety in patients with excessive sleepiness due to narcolepsy, shift work sleep disorder (SWSD), and obstructive sleep apnea/hypopnea syndrome (OSAHS; as an adjunct to regular nCPAP use) by examining its effects on blood pressure (BP) and heart rate (HR) in 7 randomized, double-blind, placebo-controlled trials.
Systolic and diastolic BP and HR data were pooled and analyzed from 7 placebo-controlled studies of modafinil: 2 studies in narcolepsy, 3 studies in OSAHS, and 2 studies in SWSD. In addition, patients in the 3 studies in OSAHS were grouped into quartiles according to baseline BP and grouped based on prior diagnosis of hypertension (n=541). Incidence of hypertension was also determined for each dose of study medication and changes in BP and HR assessed.
Modafinil therapy was not associated with clinically significant changes in BP compared with placebo in the pooled data from the 7 trials, in OSAHS patients with a history of hypertension, or in those OSAHS patients with the highest BP prior to study initiation. There were no dose-related trends in BP or HR. Retrospective calculations determined that there was 98% power to detect 5 mmHg or 5 bpm change.
Modafinil therapy was not associated with clinically relevant changes in BP or HR in patients with excessive sleepiness associated with narcolepsy, OSAHS, or SWSD, including in patients with controlled hypertension or elevated BP.
Modafinil is a well-tolerated therapy that can be used to safely and effectively improve wakefulness in patients with specific sleep-wake disorders without the risk of altering blood pressure or heart rate, even in patients with controlled hypertension. In light of the risk intrinsic to these disorders associated with excessive sleepiness, this favorable safety profile represents an important clinical characteristic of the therapy.Sponsored by Cephalon, Inc., West Chester, PA.
J. Sackner-Bernstein, Cephalon, Inc.