Drug-Induced Orthostatic Hypotension in UK Primary Care: A Self-Controlled Case Series Study.

BACKGROUND

Drug-induced orthostatic hypotension (OH) is common and increasing worldwide with rising polypharmacy. Real-world evidence is crucial for safe prescribing. We examined the risk of OH associated with commonly prescribed drugs in UK primary care among adults aged ≥60 years.

METHODS

This was a self-controlled case series using routinely collected UK primary care data from the IQVIA Medical Research Database (IMRD). Individuals with an OH diagnosis and drug exposure between 1 January 2000 and 31 December 2018 were included. Drug classes potentially causing OH were coded by British National Formulary sub-chapters. Incidence rate ratios (IRRs) of OH were compared across a 90-day pre-exposure period and three post-prescription risk periods (day 1-28; day 29-56; day 57+) against periods outside these risk periods (reference period).

RESULTS

Of 2,597,077 eligible individuals, 41,005 (1.6%) had a first-recorded OH diagnosis; 51% were women. Increased OH risk was associated with initiation of all cardiovascular system (CVS), central nervous system (CNS), and urinary retention drugs, and some anti-diabetic drugs. Across most classes, OH risk peaked sharply after initiation (day 1-28) and then declined. Drugs causing OH via sympathetic inhibition, diuresis, or mixed mechanisms had the highest risk (eg, uroselective alpha-blockers: IRR 4.94, 95% CI 4.38-5.58) during day 1-28. Vasodilation-causing drugs had lower risk (eg, calcium-channel blockers: IRR 1.88, 95% CI 1.58-2.23). An increased OH risk was observed before drug initiation when the indication was an independent OH cause (eg, loop diuretics for heart failure: IRR 1.74, 95% CI 1.59-1.91).

CONCLUSION

This study provides insights into OH risk across 17 drug classes in older adults, considering timing, drug system, and mechanism. Consistent trends show that OH risk peaked in the first 4 weeks post-initiation and reduced thereafter. Drugs causing OH through sympathetic inhibition, diuresis, or mixed mechanisms carried the greatest risk. Elevated OH risk in the pre-exposure period may suggest underlying indications that independently cause OH. These findings have important implications for primary care.