Use of droxidopa for the long-term treatment of neurogenic orthostatic hypotension
Bibliographic record
Abstract
This commentary refers to ‘2018 ESC guidelines for the diagnosis of syncope’, by M. Brignole et al., pages 1883–1948. Orthostatic hypotension (OH) can cause serious and potentially disabling symptoms and is associated with an increased risk of morbidity and mortality, particularly because of hazards from falls.1 The 2018 European Society of Cardiology (ESC) guidelines for the diagnosis and management of syncope provide clinicians with important updates regarding the recognition and treatment of OH.2 These guidelines outline the utility of droxidopa as a treatment for symptomatic OH due to autonomic failure [neurogenic OH (nOH)] based on data from short-term Phase 3 clinical trials. Recent data from a 12-month open-label extension study of droxidopa in patients with symptomatic nOH suggest the durability of benefits with long-term droxidopa treatment, including sustained increases in standing blood pressure and, more importantly, sustained improvements in patient-reported assessments of nOH symptom severity, in symptom effect on daily activities, and in the Clinical Global Impressions scale.3 The long-term efficacy of droxidopa treatment was also evaluated in a 6-month prospective study of patients with nOH initiating droxidopa treatment. This patient cohort reported improvements in falls, functionality, depressive symptoms, and health-related quality of life (HRQoL) with droxidopa treatment.4 Specifically, fewer patients reported a fall in the 1 month after initiating droxidopa treatment vs. the month before treatment (43% vs. 53%; P = 0.004); this reduced rate of falls was maintained at 6 months (40%; P = 0.034 vs. baseline). Other patient-reported assessments also showed significant improvements, including better functionality (Sheehan Disability Scale global scores, P ≤ 0.001), fewer depressive symptoms (Patient Health Questionnaire-9 scores, P < 0.01), and improved HRQoL (Short Form-8 scores, P ≤ 0.01). Taken together, the results of these studies suggest that long-term treatment with droxidopa provides sustained benefits to patients with nOH, although there are limitations due to the lack of parallel control groups and the self-reported nature of the data. As noted in the ESC guidelines,2 further research into treatment options for OH and the clinical effects of droxidopa is warranted to better guide effective management of patients with this challenging clinical condition. Editorial support was provided by CHC Group (North Wales, PA, USA). Editorial support was funded by Lundbeck. S.R.R. is a network investigator of the Cardiac Arrhythmia Network of Canada (CANet; London, Ontario, Canada). Conflict of interest: S.R.R. is a consultant/advisory board member for Lundbeck, GE Healthcare, Allergan Pharmaceuticals, Abbott Medical, and Boston Scientific Corporation. L.A.H. is an employee of Lundbeck.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.015 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.005 | 0.007 |
| Insufficient payload (model declined to judge) | 0.007 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".