Commonly prescribed drugs linked to orthostatic hypotension risk: Study
People with polypharmacy could benefit from postural blood pressure (BP) monitoring. UK: The risk of orthostatic hypotension (OH) was found to be significantly increased with a variety of medications, particularly sympathetic inhibitors, according to the findings of a systematic review and meta-analysis published in PLOS Medicine
Drugs causing sympathetic inhibition were tied to significantly increased odds of OH (beta-blockers, TCAs, antipsychotics, alpha-blockers), while most vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs, SGLT-2 inhibitors) were tied to small nonsignificant differences in odds of OH, compared to placebo.
The researchers found that beta-blockers and TCAs were associated with a 6- to 7-fold increased odds of OH compared to placebo. Alpha-blockers, second-generation antipsychotics, centrally acting antihypertensives, and SGLT-2 inhibitors were associated with up to 2-fold increased risk of OH, compared to placebo. There was no difference in odds of OH with CCBs, ACE inhibitors/ARBs, and SSRIs compared to placebo.
Orthostatic hypotension is a common side effect of drugs that causes a reduction in BP on standing. This results in reduced cerebral blood flow that is linked to falls, strokes, cognitive impairment, and increased mortality. Over 250 medications are shown to be associated with OH. However, there is conflicting evidence on the extent to which different drug groups are associated with OH as a side effect. Also, there are no systematic reviews providing an overview of which drugs are associated with OH.
Cini Bhanu, Affiliation Research Department of Primary Care and Population Health, University College London, United Kingdom, and colleagues conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing a drug to placebo, including 69 trials comprising 27,079 participants, to address the extent to which specific medications are associated with OH.
The study revealed the following findings:
- Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76; OR 6.30).
- Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo.
- There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo.
Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting.
The researchers concluded, "drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring."
Bhanu C, Nimmons D, Petersen I, Orlu M, Davis D, Hussain H, et al. (2021) Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials. PLoS Med 18(11): e1003821. https://doi.org/10.1371/journal.pmed.1003821