Orthostatic hypotension: a pragmatic guide to diagnosis and treatment

Gibbon, Jake Ryan; Frith, James

doi:10.1136/dtb.2020.000056

Cited by 7 publications

(14 citation statements)

References 30 publications

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“…Both these groups induce OH through combined mechanisms of sympathetic inhibition and vasodilatory effects suggesting that OH risk rises with cumulative drug targets. This suggests that coprescription of drugs with the potential to cause OH may also result in cumulative harm, in keeping with a growing body of evidence [ 3 , 35 ].…”

Section: Discussionsupporting

confidence: 57%

“… 5 ], fractures [ 5 ], ischaemic events [ 2 , 5 ], cognitive impairment [ 6 ], and mortality [ 5 ]. Over 250 medications are associated with OH [ 3 ], and the incidence of OH increases with advancing age [ 6 ]. As polypharmacy rises worldwide in the ageing population [ 7 ], drug-induced OH is of greater concern.…”

Section: Introductionmentioning

confidence: 99%

“…Orthostatic hypotension (OH), defined as a reduction in systolic blood pressure (BP) of �20 mm Hg or diastolic BP of �10 mm Hg within 3 minutes of assuming an erect posture [1], is estimated to affect 30% to 70% of older adults [2] and is commonly associated with use of medications [3]. OH and its resulting cerebral hypoperfusion is linked to falls [4.5], fractures [5], ischaemic events [2,5], cognitive impairment [6], and mortality [5].…”

Section: Introductionmentioning

confidence: 99%

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Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials

et al. 2021

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Background Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear. Methods and findings We conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel–Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). 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 study protocol is publicly available on PROSPERO (CRD42020168697). Conclusions Medications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. 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.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials

et al. 2021

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“…Orthostatic hypotension (OH) is defined as a sustained drop in blood pressure (BP, ≥ 20 mmHg systolic BP or ≥ 10 mmHg diastolic BP) within 3 min of standing upright [ 1 ]. It increases the risk of falls and all-cause mortality and is associated with disabling symptoms [ 2 , 3 ]. It is very common, especially in older people and in those with chronic disease [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Neurogenic OH (nOH), a pathophysiological subtype of OH, results from central or peripheral autonomic dysfunction, leading to impairment of baroreflex-mediated vasoconstriction of skeletal muscle and splanchnic vasculature [ 5 ]. Both pharmacological and non-pharmacological treatments for nOH are poorly evidenced, and issues with efficacy, adherence and tolerability are common, creating a need for a better-quality evidence base [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

The effects of caffeine in adults with neurogenic orthostatic hypotension: a systematic review

Gibbon

Frith

2021

Clin Auton Res

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Purpose To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults. Methods Eight electronic databases were searched in January 2021. Original research studies or case reports involving adults with neurogenic orthostatic hypotension were included if caffeine was an intervention and outcomes included symptoms, blood pressure or adverse effects. Relevant studies were screened and underwent qualitative analysis. Insufficient reporting precluded meta-analysis. Results Five studies were identified: four crossover studies and one case report summation. Study size ranged from 5 to 16 participants. Participants had neurogenic orthostatic hypotension, with a mean standing systolic blood pressure of 86 mmHg. Two studies evaluated caffeine alone. Three studies administered caffeine in combination with ergotamine. Caffeine dose ranged from 100 to 300 mg. Nature and timing of outcomes measured varied between studies, with measurements being recorded from 30 to 480 min after intervention. Caffeine/ergotamine improved symptoms in one study and reduced orthostatic blood pressure drop in two studies. Caffeine/ergotamine increased seated blood pressure in three studies, whilst the results for caffeine alone were inconsistent. No serious adverse events were reported. All studies demonstrated high risk of bias. Conclusion Caffeine should only be considered as a treatment for adults with neurogenic orthostatic hypotension when evidence-based treatments have been exhausted. Systematic review registration PROSPERO ID: CRD42020124589. Date of registration: 30/10/2020

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Drug‐induced orthostatic hypotension: Cluster analysis of co‐prescription patterns in older people in UK primary care

Bhanu,

Petersen,

Orlu

et al. 2023

Pharmacoepidemiology and Drug

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PurposeOver 250 medications are reported to cause orthostatic hypotension, associated with serious adverse outcomes in older adults. Studies suggest a harmful cumulative risk of orthostatic hypotension with multiple medication use. However, there is limited evidence on the potential for harm in practice, particularly which drugs is co‐prescribed and may increase risk of orthostatic hypotension.MethodsRetrospective cohort study and cluster analysis using general practice data from IQVIA Medical Research Data (IMRD) in patients aged ≥50 contributing data between 1 January 2018 and 31 December 2018. Thirteen drug groups known to be associated with orthostatic hypotension by mechanism, were analyzed and clusters generated by sex and age‐band.ResultsA total of 602 713 individuals aged ≥50 with 283 912 (47%) men and 318 801 (53%) women were included. The most prevalent prescriptions that might contribute to orthostatic hypotension were ACE inhibitors, calcium‐channel blockers, beta‐blockers, selective serotonin reuptake inhibitors and uroselective alpha‐blockers. We identified distinct clusters of cardiovascular system (cardiovascular system) drugs in men and women at all ages. cardiovascular system plus psychoactive drug clusters were common in women at all ages, and in men aged ≤70. cardiovascular system plus uroselective alpha‐blockers were identified in men aged ≥70.ConclusionsDistinct clusters of drugs associated with orthostatic hypotension exist in practice, which change over the life course. Our findings highlight potentially harmful drug combinations that may cause cumulative risk of orthostatic hypotension in older people. This may guide clinicians about the potential of synergistic harm and to monitor for orthostatic hypotension if using combinations of cardiovascular system drugs, cardiovascular system plus psychoactive drugs and/or alpha‐blockers—particularly in patients aged ≥70 or at high‐risk due to comorbidity. Future research should consider quantifying the risk of drug‐induced orthostatic hypotension with such drug combinations.

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Orthostatic hypotension: a pragmatic guide to diagnosis and treatment

Cited by 7 publications

References 30 publications

Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials

Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials

The effects of caffeine in adults with neurogenic orthostatic hypotension: a systematic review

Drug‐induced orthostatic hypotension: Cluster analysis of co‐prescription patterns in older people in UK primary care

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