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

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.

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).

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).

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.