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- W2893280078 abstract "There are few effective therapies for vasovagal syncope. The norepinephrine transporter (NET) reuptakes norepinephrine from sympathetic synapses. Pharmacological NET inhibition increases sympathetic tone, may increase vascular tone and heart rate, and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and widely available NET inhibitor. We tested the hypothesis that Atomoxetine prevents tilt-induced vasovagal syncope. The POST6 study was a placebo-controlled, parallel-group, randomized trial of Atomoxetine (n=27) vs. placebo (n=29). Vasovagal syncope patients were given two doses of study drug 12 hours apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate and blood pressure were recorded with a fingertip cuff. Patients were 35±14 years (73% Female) with a median of 12 lifetime faints, and a median of 3 faints in the last year. Significantly fewer vasovagal syncope patients fainted with atomoxetine than with placebo 8/29 vs. 17/27%; p=0.015, Fisher exact; Odds Ratio 0.22 (CI 0.073, 0.693; p=0.009), but there was no difference in the likelihood of presyncope 21/29 vs 21/27; p=0.76). The logrank hazard ratio for syncope with Atomoxetine was 0.40 (95% CI: 0.18-0.87). Patients with syncope had lower trough systolic blood pressure than subjects with presyncope (mean 57 vs 72 mm Hg, p=0.002), and this was due to lower trough heart rates than subjects with presyncope (mean 58 vs 93 bpm, p=0.001), not stroke volume or systemic resistance. The major effect of Atomoxetine vs placebo during presyncope or syncope was to preserve systolic blood pressure (mean 55 vs 76 mm Hg, p=0.003) and heart rate (mean 95 vs 62 bpm, p=0.002). Systematic vascular resistance and stroke volume did not vary with presyncope vs syncope or Atomoxetine vs placebo treatment The main effect of Atomoxetine was to blunt bradycardia, thereby increasing cardiac index and blood pressure. NET inhibition significantly decreased the risk of tilt-induced syncope in vasovagal syncope subjects, mainly by blunting reflex bradycardia.View Large Image Figure ViewerDownload Hi-res image Download (PPT)" @default.
- W2893280078 created "2018-10-05" @default.
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- W2893280078 date "2018-10-01" @default.
- W2893280078 modified "2023-09-27" @default.
- W2893280078 title "A PROOF OF PRINCIPLE STUDY OF ATOMOXETINE FOR THE PREVENTION OF VASOVAGAL SYNCOPE: POST 6" @default.
- W2893280078 doi "https://doi.org/10.1016/j.cjca.2018.07.198" @default.
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