# Impact of COVID‑19 infection on subsequent prescriptions of autonomic dysfunction pharmacotherapy: a nationwide propensity‑score‑matched Cohort study in Japan

## TL;DR

This study finds that people who had COVID-19 in Japan were more likely to be prescribed medications for autonomic dysfunction, like orthostatic hypotension, for up to a year after infection.

## Contribution

The study is the first nationwide analysis showing a long-term link between COVID-19 and increased use of autonomic dysfunction medications.

## Key findings

- COVID-19 patients had a 36% higher risk of being prescribed autonomic dysfunction medications compared to controls.
- The risk of prescription persisted for over a year after infection.
- Fludrocortisone showed the strongest association with increased prescriptions among the studied drugs.

## Abstract

Autonomic dysfunction, including orthostatic hypotension and postural tachycardia syndrome, has emerged as a COVID-19 complication. This nationwide propensity score-matched cohort study investigated COVID-19’s impact on subsequent prescriptions of autonomic dysfunction in Japan.

Using a claims database covering 16 million residents identified between 2020 and 2022, propensity-score matching (PSM) created comparable groups of COVID-19 patients and controls. PSM used age, sex, calendar month, comorbidities, and baseline medications, with nearest-neighbor 1:1 with replacement. The primary composite outcome was the first outpatient prescription of midodrine, fludrocortisone, amezinium methylsulfate, and droxidopa. Cox proportional hazards models yielded hazard ratios (HRs) with 95% confidence intervals (CIs). Effect modifications were examined by subgroups.

Among 3,074,329 matched pairs, over a median follow-up of 8 months, 13011 composite outcome were observed, and COVID-19 infection was associated with a 36% relative increase in prescriptions (HR 1.36, 95%CI 1.32–1.41). The risk persisted beyond one year, with the strongest association observed for fludrocortisone (576 events, HR 1.71, 95%CI 1.44–2.02), although the frequency was the highest in midodrine prescription (7009 events, HR 1.28, 95%CI 1.22–1.34). Subgroup analysis revealed higher risks among older individuals, males, those with myocardial infarction, heart failure, and antihypertensive medications.

COVID-19 infection is significantly associated with increased initiation of pharmacotherapy for autonomic dysfunction, with sustained risk beyond one year. These findings highlight the to manage autonomic dysfunction among COVID-19 survivors and informing clinical care and public health planning.