Pavic_2025_Open.Heart_12_

BACKGROUND: Current pharmacological approaches for the treatment of orthostatic hypotension (OH) may detrimentally affect supine blood pressure (BP). This side effect is often unacceptable and limits the utility of medical management. Pyridostigmine has been proposed as a potential treatment alternative which may improve OH without worsening supine hypertension. This systematic review and meta-analysis aimed to evaluate the currently available data regarding the use of pyridostigmine in the treatment of all-cause OH. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, EMBASE, Cochrane and SCOPUS were searched for publications until 4 June 2024. A random-effects model was used for meta-analysis. RESULTS: The search returned 715 results, of which 6 randomised controlled trials met the inclusion criteria. Several studies reported a statistically significant improvement in orthostatic BP following pyridostigmine administration. Two studies found that pyridostigmine had no effect on standing BP among patients with severe autonomic failure. One study suggested that combination therapy with atomoxetine may elicit a synergistic effect. In most studies, pyridostigmine had no significant effect on supine BP. Adverse effects were minimal across the included studies. The pooled results from the meta-analysis showed that while pyridostigmine alone resulted in lower systolic and diastolic orthostatic drop, neither result was statistically significant. However, when pyridostigmine is combined with midodrine, this demonstrated a significant improvement in systolic orthostatic drop. CONCLUSIONS: Pyridostigmine may be useful in the management of OH, particularly in patients with supine hypertension. The standing BP response to pyridostigmine may be greater in patients who have a relatively preserved baroreflex function and sympathetic reserve. PROSPERO REGISTRATION NUMBER: CRD42024555402.