Efficacy of pharmacological management of orthostatic hypotension- a systematic review and meta-analysis

Authors: Danny Jenkins¹, Spoorthy Kulkarni², Holly Pavey³, Veronica Phillips⁴, Fraz Mir^2,5

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.