Carbidopa for Afferent Baroreflex Failure in Familial Dysautonomia: A Double-Blind Randomized Crossover Clinical...

Area of Science:

• Cardiovascular Physiology
• Autonomic Nervous System Disorders
• Pharmacology

Background:

• Familial dysautonomia is characterized by afferent arterial baroreflex lesions, leading to significant blood pressure variability and organ damage.
• Hypertensive surges in these patients result from excessive peripheral catecholamine release, lacking effective treatments.
• Carbidopa, a DOPA-decarboxylase inhibitor, can suppress peripheral catecholamine production.

Purpose of the Study:

• To evaluate the efficacy of carbidopa in inhibiting catecholamine-induced hypertensive surges in patients with severe afferent baroreflex failure.
• To assess carbidopa's impact on blood pressure variability and norepinephrine excretion in familial dysautonomia.

Main Methods:

• A double-blind, randomized crossover trial involving 22 patients with familial dysautonomia.
• Patients received high-dose carbidopa (600 mg/day), low-dose carbidopa (300 mg/day), or placebo for three 4-week periods.
• Measurements included 24-hour urinary norepinephrine excretion and blood pressure variability (SD of systolic BP).

Main Results:

• Both high and low doses of carbidopa significantly suppressed 24-hour urinary norepinephrine excretion compared to placebo (P=0.0075).
• Carbidopa significantly reduced the standard deviation of systolic blood pressure variability (low dose: 17±4 mmHg; high dose: 18±5 mmHg) versus placebo (23±7 mmHg; P=0.0013).
• A significant reduction in systolic blood pressure peaks was observed with carbidopa treatment (P=0.0015).

Conclusions:

• Carbidopa, at both tested doses, effectively reduces blood pressure variability and hypertensive surges in patients with congenital afferent baroreflex failure.
• The drug was well-tolerated and demonstrated similar efficacy at high and low doses.
• Findings suggest carbidopa may benefit patients with acquired baroreflex lesions as well.