P408: Treatment Of Orthostatic Hypotension With Pyridostigmine: Relevance To Supine Hypertension

Supine hypertension, a common comorbidity in patients with orthostatic hypotension (OH), creates a management challenge because the treatment of one condition can worsen the other. Treatment of OH with the acetylcholinesterase inhibitor pyridostigmine has the advantage of preferentially increasing upright blood pressure (BP) by facilitating autonomic ganglia neurotransmission. We did a retrospective analysis of 37 patients with neurogenic OH (65±2 yr, 21 men) to study the efficacy of pyridostigmine 60 mg (defined as the increase in upright systolic BP [SBP] 1-hr postdrug) and determine clinical predictors of efficacy. Pyridostigmine increased upright SBP by 4 (-6 to 11 mmHg, median, IQR). Pyridostigmine efficacy was inversely correlated with the severity of OH (the SBP drop on standing, r 2 =0.4, p=0.022) and with the magnitude of autonomic impairment, the ratio of the increase in heart rate on standing divided by the drop in SBP, (r 2 =0.32, p=0.044) only in patients with central autonomic failure and intact efferent sympathetic pathways (multiple system atrophy, MSA; n=13), but not in patients with pure autonomic failure (PAF; n=24). Pyridostigmine efficacy was negatively correlated to supine BP (r 2 =0.20, p=0.006; Figure). In conclusion, pyridostigmine was less effective in patients with severe autonomic impairment and those with supine hypertension, who are most likely to benefit from the preferential increase in upright BP produced by the drug. PAF patients had severe OH (-74±6 vs. -56±8 mmHg in MSA), and our results may not reflect patients with milder OH.