Efficacy of pharmacological management of orthostatic hypotension- a
systematic review and meta-analysis
Authors: Danny Jenkins1, Spoorthy
Kulkarni2, Holly Pavey3, Veronica
Phillips4, Fraz Mir2,5
1 Guy’s and St Thomas’ NHS Foundation Trust, London,
London, UK
2 Cambridge University Hospitals NHS Foundation Trust,
Cambridge, UK
3 University of Cambridge, Cambridge, UK
4 University of Cambridge, Medical Library, Cambridge,
Cambridgeshire, UK
5 School of Clinical Medicine, University of
Cambridge, Cambridge, UK
Contributions
All authors have given final approval of this version of this
manuscript.
Author contributions:
Review conception and design: SK, FM, DJ
Database searching and study identification: VP, SK
Data extraction: DJ, SK
Drafting of the manuscript: DJ and SK
Statistical guidance: HP
Joint first co-authors: DJ and SK
Corresponding author: SK
Critical revision of the manuscript and overall responsibility: FM
Conflicts of interest: No disclosures
Funding: nil towards this study
SK is funded by UKRI-MRC Secondment Award (MR/W003538/1)
Abstract:
Introduction
Orthostatic hypotension (OH) is associated with cardiovascular mortality
and morbidity. Non-pharmacological and pharmacological therapies are
employed in the management of OH. The aim of this systematic review and
meta-analysis is to provide an up-to-date review of the efficacy
parameters of pharmacological therapies.
Methods
Medline, Embase, Cochrane Library, and Scopus were searched
(inception-July 2021), and published articles with randomized control
trials, meeting inclusion and exclusion criteria were quality assessed
(Risk of Bias 2 tool). Assessment for trends in patient-related outcome
measures and postural blood pressure improvement was undertaken. Studies
reporting postural systolic blood pressure (SBP) before and after
intervention in comparison to placebo were included in a meta-analysis
using inverse -variance in a random-effects model.
Results
19 articles were included in the systematic review. The orthostatic
symptoms questionnaire (OHQ) was the most common patient-related outcome
measure utilized in trials. Six studies included in the meta-analysis
demonstrated that pharmacological therapies (pyridostigmine, midodrine,
atomoxetine, yohimbine) improved postural SBP compared to placebo, with
a mean rise of 12.50 mmHg [95% CI: 6.01, 18.98; p
value<0.001, I2 =97%]. Midodrine showed
the highest impact on SBP, with a mean SBP of 16.11 mmHg [95% CI:
5.59, 26.63; p=0.003, I2 =99%].
Conclusions
Pharmacological treatment can significantly increase postural SBP,
however with significant heterogeneity related to trial designs. Further
efforts to homogenize outcome measures, incorporating symptom
improvement and reduction in the postural drop and testing for a
prolonged duration of therapy would strengthen the evidence, and improve
the translatability of findings in clinical settings.