Cardiovascular Safety of Droxidopa in Patients With Symptomatic Neurogenic Orthostatic Hypotension.
The norepinephrine prodrug droxidopa improves symptoms of neurogenic orthostatic hypotension, a condition that is associated with diseases of neurogenic autonomic failure (e.g., Parkinson disease, multiple system atrophy, pure autonomic failure). These conditions are more prevalent in older patients who also have cardiovascular co-morbidities. Hence, we evaluated the cardiovascular safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension who participated in randomized controlled studies (short-term studies of 1 to 2 weeks and an intermediate 8- to 10-week study) and long-term open-label studies. Rates of cardiovascular adverse events (AEs) for patients treated with droxidopa were 4.4% in the intermediate study and 10.8% in the long-term open-label studies. Adjusting for exposure time, cardiovascular AE rates were 0.30 events/patient-year in the short-term and intermediate studies and 0.15 events/patient-year in the long-term open-label studies. The incidence of treatment discontinuation due to blood pressure-related events was approximately 2.5%. Among patients with a history of cardiac disorders at baseline, the rates of cardiovascular-related and blood pressure-related AEs were nominally higher with droxidopa compared to placebo. Most of these events were minor atrial arrhythmias; none were major adverse cardiovascular events or deaths. In conclusion, small increases in cardiovascular AEs were observed with droxidopa compared to placebo; this was most evident in patients with preexisting cardiac disorders.
Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut. Electronic address: wwhite@uchc.edu.
William B
WB
White
Department of Neurology, University of South Florida, Tampa, Florida.
Robert A
RA
Hauser
Lundbeck LLC, Deerfield, Illinois.
Gerald J
GJ
Rowse
Lundbeck LLC, Deerfield, Illinois.
Adam
A
Ziemann
Lundbeck LLC, Deerfield, Illinois.
L Arthur
LA
Hewitt
D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications*; D015103:Droxidopa / Q000627:therapeutic use*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000150:complications / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D015103:Droxidopa