Long-term efficacy of antihypotensive medications for neurogenic orthostatic hypotension – Real-world data from patients with alpha-synucleinopathies

<h3>Introduction</h3> Treatment of neurogenic orthostatic-hypotension (nOH) relies on consensus-based approaches; real-world data on long-term efficacy and safety are lacking. We evaluated response to anti-hypotensives in a longitudinal cohort of patients with synuclein-related nOH (PAF, PD, DLB and MSA). <h3>Methods</h3> Severity of cardiovascular autonomic failure was assessed with quantitative testing. Response to medications was measured with a semi-composite questionnaire assessing the number of falls/month and hospitalizations/trimester, burden of orthostatic symptoms, quality of life (OHQ, SF-36, PGI scale) and BP monitoring. Demographic measures are reported as median + IQR, all other measures as mean ± SD. <h3>Results</h3> 101 patients completed the questionnaire (49-PAF, 27-PD, 21-MSA and 4-DLB). 61 patients were on long-term treatment; 40 on non-pharmacological measures. Number of falls and hospital admission were 2 ± 12 and 0.3 ± 1 respectively. OHQ composite-score (range:1-10) was 7.24 ± 1.7. SF36 physical and mental composite-scores (range:0-100) were 33.2 ± 37.5 and 38.9 ± 37.8 respectively. PGI score (range:1-7) was 4.7 ± 1.4. The magnitude of nOH was 56/27 (± 34/19)mmHg in treated patients, compared to 29/6 (± 22/11)mmHg in those untreated. <h3>Conclusion</h3> Despite multiple anti-hypotensive use, two-thirds of patients were significantly symptomatic with nOH, as corroborated by falls rates and hospital admissions. These findings emphasized the critical nature of nOH, its current gaps in pharmacological management and its profound impact on patients‘ daily functioning.