scholarly journals Characterization of the changes in supine blood pressure with long‐term use of droxidopa in patients with neurogenic orthostatic hypotension

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
L. Arthur Hewitt ◽  
Annika Lindsten ◽  
Stephen Gorny ◽  
Meghana Karnik‐Henry ◽  
Steven Kymes ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Neurogenic Orthostatic Hypotension ◽  
Supine Blood Pressure

scholarly journals Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial

2021 ◽  
Author(s):  
Horacio Kaufmann ◽  
Ross Vickery ◽  
Whedy Wang ◽  
Jitendra Kanodia ◽  
Cyndya A. Shibao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Orthostatic Hypotension ◽  
Controlled Study ◽  
Neurogenic Orthostatic Hypotension ◽  
Median Dose ◽  
Double Blind ◽  
Supine Blood Pressure ◽  
Part C ◽  
Standing Blood Pressure

Abstract Purpose In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension. Methods A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety. Results Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration. Conclusion Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure. Trial registration NCT02705755 (first posted March 10, 2016).

603 CHALLENGES IN THE MANAGEMENT OF SEVERE ORTHOSTATIC HYPOTENSION ASSOCIATED WITH SUPINE HYPERTENSION IN A PATIENT WITH AUTONOMIC DYSFUNCTION ON BACKGROUND OF NASOPHARYNGEAL CARCINOMA AND TYPE II DIABETES MELLITUS

2021 ◽  
Vol 50 (Supplement_2) ◽  
pp. ii14-ii18
Author(s):  
Q M N Rachel ◽  
K Mamun ◽  
M H Nguyen
Keyword(s):  
Blood Pressure ◽  
Nasopharyngeal Carcinoma ◽  
Orthostatic Hypotension ◽  
Carotid Sinus ◽  
Blood Pressure Monitoring ◽  
Pharmacological Interventions ◽  
Supine Hypertension ◽  
Neck Irradiation ◽  
Baroreflex Failure

Abstract Introduction Combined chemotherapy and radiotherapy increases long term survival in patients with nasopharyngeal carcinoma. However, radiotherapy of the carotid sinus or brain stem can evolve labile hypertension and orthostatic intolerance from chronic baroreflex failure. Diabetes would also cause this neuropathy. Management of patients with Supine hypertension-Orthostatic hypotension can be very challenging. Methods A case report was done on a 71-year-old man with metastatic nasopharyngeal carcinoma status post radiation therapy who was admitted with severe supine hypertension-orthostatic hypotension. Patient was managed with both non-pharmacological and pharmacological methods, and monitored for postural symptoms, complications of severe supine hypertension—which has been linked to left ventricular hypertrophy and kidney dysfunction, and placed on 24 hour ambulatory blood pressure monitoring to aid in management so as to prevent hypertension induced organ damage. Results This review outlines the pathophysiology of Supine hypertension-Orthostatic hypotension, treatment complications and potential management strategies recommendations for this group of patients. It revealed the benefit of having a 24 hour ambulatory blood pressure monitoring, which provides insight on the timing and magnitude of an individual’s blood pressure fluctuations throughout the day so as to further guide management. Conclusion Chronic baroreflex failure is a late sequela of neck irradiation for naso-pharyngeal carcinoma due to accelerated atherosclerosis in the region of the carotid sinus baroreceptor. Treatment goal is achieved with adequate control of pre-syncopal symptoms and prevention of long term complications. Non-pharmacological interventions remain the first line of therapy, followed by pharmacological interventions as necessary. Nonetheless, management of blood pressure in these elderly patients with baroreflex dysfunction remains challenging and should be individualized. Moving forward, a prospective study on the incidence of late onset, iatrogenic baroreflex failure as a late complication of neck irradiation and its particular relationship to carotid arterial rigidity should be conducted to increase awareness, timely diagnosis and management of the condition among physicians.

Standing and Supine Blood Pressure Outcomes Associated With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: A Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials

2018 ◽  
Vol 52 (12) ◽  
pp. 1182-1194 ◽  
Author(s):  
Jack J. Chen ◽  
Yi Han ◽  
Jonathan Tang ◽  
Ivan Portillo ◽  
Robert A. Hauser ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Fixed Effects ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Mixed Treatment Comparison ◽  
Neurogenic Orthostatic Hypotension ◽  
Supine Hypertension ◽  
Treatment Comparison ◽  
Mixed Treatment

Background: The comparative effects of droxidopa and midodrine on standing systolic blood pressure (sSBP) and risk of supine hypertension in patients with neurogenic orthostatic hypotension (NOH) are unknown. Objective: To perform a Bayesian mixed-treatment comparison meta-analysis of droxidopa and midodrine in the treatment of NOH. Methods: The PubMed, CENTRAL, and EMBASE databases were searched up to November 16, 2016. Study selection consisted of randomized trials comparing droxidopa or midodrine with placebo and reporting on changes in sSBP and supine hypertension events. Data were pooled to perform a comparison among interventions in a Bayesian fixed-effects model using vague priors and Markov chain Monte Carlo simulation with Gibbs sampling, calculating pooled mean changes in sSBP and risk ratios (RRs) for supine hypertension with associated 95% credible intervals (CrIs). Results: Six studies (4 administering droxidopa and 2 administering midodrine) enrolling a total of 783 patients were included for analysis. The mean change from baseline in sSBP was significantly greater for both drugs when compared with placebo (droxidopa 6.2 mm Hg [95% CrI = 2.4-10] and midodrine 17 mm Hg [95% CrI = 11.4-23]). Comparative analysis revealed a significant credible difference between droxidopa and midodrine. The RR for supine hypertension was significantly greater for midodrine, but not droxidopa, when compared with placebo (droxidopa RR = 1.4 [95% CrI = 0.7-2.7] and midodrine RR = 5.1 [95% CrI = 1.6-24]). Conclusion and Relevance: In patients with NOH, both droxidopa and midodrine significantly increase sSBP, the latter to a greater extent. However, midodrine, but not droxidopa, significantly increases risk of supine hypertension.

scholarly journals Neurogenic Orthostatic Hypotension: State of the Art and Therapeutic Strategies

2020 ◽  
Vol 14 ◽  
pp. 117954682095341
Author(s):  
Dinesh K Kalra ◽  
Anvi Raina ◽  
Sumit Sohal
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Clinical Features ◽  
Autonomic Dysfunction ◽  
State Of The Art ◽  
Therapeutic Strategies ◽  
Review Article ◽  
Neurogenic Orthostatic Hypotension ◽  
Standing Blood Pressure ◽  
Secondary Causes

Neurogenic orthostatic hypotension (nOH) is a subtype of orthostatic hypotension in which patients have impaired regulation of standing blood pressure due to autonomic dysfunction. Several primary and secondary causes of this disease exist. Patients may present with an array of symptoms making diagnosis difficult. This review article addresses the epidemiology, pathophysiology, causes, clinical features, and management of nOH. We highlight various pharmacological and non-pharmacological approaches to treatment, and review the recent guidelines and our approach to nOH.

scholarly journals Neurogenic Orthostatic Hypotension. Lessons From Synucleinopathies

2020 ◽  
Author(s):  
Juan Francisco Idiaquez ◽  
Juan Idiaquez ◽  
Juan Carlos Casar ◽  
Italo Biaggioni
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Treatment Options ◽  
Lewy Body Dementia ◽  
Cerebral Hypoperfusion ◽  
Neurogenic Orthostatic Hypotension ◽  
Compression Garments ◽  
Novel Treatments ◽  
Mild Disease ◽  
Noradrenergic Fibers

Abstract Maintenance of upright blood pressure critically depends on the autonomic nervous system and its failure leads to neurogenic orthostatic hypotension (NOH). The most severe cases are seen in neurodegenerative disorders caused by abnormal α-synuclein deposits: multiple system atrophy (MSA), Parkinson’s disease, Lewy body dementia, and pure autonomic failure (PAF). The development of novel treatments for NOH derives from research in these disorders. We provide a brief review of their underlying pathophysiology relevant to understand the rationale behind treatment options for NOH. The goal of treatment is not to normalize blood pressure but rather to improve quality of life and prevent syncope and falls by reducing symptoms of cerebral hypoperfusion. Patients not able to recognize NOH symptoms are at a higher risk for falls. The first step in the management of NOH is to educate patients on how to avoid high-risk situations and providers to identify medications that trigger or worsen NOH. Conservative countermeasures, including diet and compression garments, should always precede pharmacologic therapies. Volume expanders (fludrocortisone and desmopressin) should be used with caution. Drugs that enhance residual sympathetic tone (pyridostigmine and atomoxetine) are more effective in patients with mild disease and in MSA patients with spared postganglionic fibers. Norepinephrine replacement therapy (midodrine and droxidopa) is more effective in patients with neurodegeneration of peripheral noradrenergic fibers like PAF. NOH is often associated with other cardiovascular diseases, most notably supine hypertension, and treatment should be adapted to their presence.

Abstract P379: Patient and Caregiver Experiences With the Diagnosis of Neurogenic Orthostatic Hypotension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Lawrence A Hewitt ◽  
Charles H Adler ◽  
Daniel O Claassen ◽  
Christopher H Gibbons ◽  
Satish R Raj
Keyword(s):  
Orthostatic Hypotension ◽  
Autonomic Failure ◽  
Pure Autonomic Failure ◽  
Accurate Diagnosis ◽  
First Year ◽  
Neurogenic Orthostatic Hypotension ◽  
Postural Change ◽  
Sustained Reduction ◽  
Caregiver Experiences

Objective: To understand the challenges to diagnosis in patients with neurogenic orthostatic hypotension (nOH) Background: nOH is a sustained reduction in blood pressure (BP) with postural change associated with autonomic dysfunction. Despite symptoms of nOH, many patients struggle to find an accurate diagnosis. Methods: An online, US-based survey designed by the authors was conducted by Harris Poll. Eligible participants were ≥18 years of age with Parkinson disease, multiple system atrophy, or pure autonomic failure and ≥1 of the following: orthostatic hypotension (OH), nOH, low BP, OH/nOH symptoms, or were caregivers of eligible participants. Results: The survey included 363 patients and 128 caregivers. Groups were separate, where caregivers were not the caregivers to patient responders. Respondents indicated that patients experienced nOH symptoms long term (Table 1) . Most patients (69%) and caregivers (59%) reported discussing nOH symptoms with a healthcare provider (HCP) within the first year of symptom onset, but only 36% of patients and 16% of caregivers reported a formal diagnosis of OH or nOH. Of those with a formal diagnosis, the majority of patients (50%) were frustrated by the path to diagnosis and more than 40% of patients and caregivers reported that the patient saw ≥3 HCPs before diagnosis. After diagnosis, most patients (70%) and caregivers (60%) reported improved symptom management. Conclusions: This survey reveals that patients and caregivers may find the path to nOH diagnosis challenging and suggests increased awareness among HCPs is needed. Once a diagnosis is made nOH symptoms are better managed.

scholarly journals The effects of caffeine in adults with neurogenic orthostatic hypotension: a systematic review

2021 ◽  
Author(s):  
Jake Ryan Gibbon ◽  
James Frith
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Case Reports ◽  
Meta Analysis ◽  
Evidence Base ◽  
Original Research ◽  
Neurogenic Orthostatic Hypotension ◽  
Serious Adverse Events ◽  
Evidence Based Treatments

Abstract Purpose To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults. Methods Eight electronic databases were searched in January 2021. Original research studies or case reports involving adults with neurogenic orthostatic hypotension were included if caffeine was an intervention and outcomes included symptoms, blood pressure or adverse effects. Relevant studies were screened and underwent qualitative analysis. Insufficient reporting precluded meta-analysis. Results Five studies were identified: four crossover studies and one case report summation. Study size ranged from 5 to 16 participants. Participants had neurogenic orthostatic hypotension, with a mean standing systolic blood pressure of 86 mmHg. Two studies evaluated caffeine alone. Three studies administered caffeine in combination with ergotamine. Caffeine dose ranged from 100 to 300 mg. Nature and timing of outcomes measured varied between studies, with measurements being recorded from 30 to 480 min after intervention. Caffeine/ergotamine improved symptoms in one study and reduced orthostatic blood pressure drop in two studies. Caffeine/ergotamine increased seated blood pressure in three studies, whilst the results for caffeine alone were inconsistent. No serious adverse events were reported. All studies demonstrated high risk of bias. Conclusion Caffeine should only be considered as a treatment for adults with neurogenic orthostatic hypotension when evidence-based treatments have been exhausted. Systematic review registration PROSPERO ID: CRD42020124589. Date of registration: 30/10/2020

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