2. Methods
This systematic review and meta-analysis were conducted according to the
Preferred Reporting Items for Systematic Reviews and Meta-Analysis
(PRISMA) statement (Page et al., 2021).
2.1 Search Strategy and RCT
selection
The databases Medline (via Ovid), Embase (via Ovid), Cochrane Library,
and Scopus were searched from inception to July 2021, using the search
terms outlined in appendix 1. A further search on clinicaltrials.gov for
additional completed clinical trials was undertaken in May 2022. All
results were limited to English language and human studies using the
available limit functions on each database. Inclusion criteria were
published studies, randomized control trials (RCT), adults-only (≥18
years only), pharmacological intervention only. Studies were excluded if
they were phase 1 trials, non-RCT/observational design, single-arm
trials, participants <18, included animal data, in vitro
trials, or had N<10 per arm and if the outcome or impact of
the intervention was not clearly presented. The study protocol was not
registered. However, the database PROSPERO was searched before starting
the review to avoid duplication. Therapy with salt tablets was not
treated as pharmacological therapy for the purpose of this review.
2.2 Study selection
Two independent investigators (D.J. and S.K.) performed the study
selection. Titles and abstracts were screened for duplicates and
eligibility. Among the relevant abstracts, full texts were assessed for
eligibility.
2.3 Data extraction
Data extraction from the eligible studies was conducted by two
independent investigators (D.J. and S.K.). Data were collected for the
following domains: authors, journal, publication date, number of
participants in experimental and control arms, patient disease group,
study design, study duration, experimental medications and doses,
control medication and doses, route, duration of follow up, age, sex,
and the efficacy parameters as described by the authors not limiting to
baseline BP, baseline postural BP drop, post-intervention BP and
postural BP drop, symptom improvement.
2.4 Quality assessment
The included studies were quality assessed using the Risk of Bias (ROB)
2 tool from the Cochrane Collaboration (Sterne et al., 2019) for the
standard domains including randomization, deviation of intended
interventions, missing outcomes, measurement of the outcomes and
selection of reported results. The assessment was conducted by two
independent investigators (D.J. and S.K.) and any disagreements were
resolved with consultation with a third author (F.M.). Studies with a
high risk of bias in more than two domains were excluded (Figure 2).
2.5 Data synthesis and
analysis
Excel was used to perform summary and descriptive statistics. Where a
single study had multiple treatment arms of interest, the arms were
assessed separately. Review Manager 5.4 (The Cochrane Collaboration,
2020) was utilized for the meta-analysis of the studies. We used a
random-effects model with inverse-variance weighting and heterogeneity
of the studies was assessed using the I2 statistic.
Results are presented as the mean differences with 95% confidence
intervals (CI) and displayed in forest plots.